method of using a volatile antimicrobial compound against pathogens that affect meat, plants or part

专利摘要:
USE OF BENZOXABOROLS AS VOLATILE ANTIMICROBIAL AGENTS IN MEAT, PLANTS OR PARTS OF PLANTS. The present invention relates to the use of a volatile antimicrobial compound against pathogens that affect meat, plants or parts of plants. The volatile antimicrobial compounds provided include certain oxaborol compounds, for example, benzoxaborols. Delivery systems are provided to take advantage of the volatile nature of these antimicrobial compounds. Also combinations with a volatile plant growth regulator, for example, 1-methylcyclopropene, are described.
公开号:BR102014002276B1
申请号:R102014002276-7
申请日:2014-01-29
公开日:2020-10-27
发明作者:Daniel Maclean；Maurice C. H. Yap；David H. Young；Rodrigo A. Cifuentes；Richard Jacobson；Donald H. Devries
申请人:Agrofresh Inc；
IPC主号:

专利说明:

BACKGROUND OF THE INVENTION
[001] Several compounds containing an oxaborol ring have been described previously. However, there is no teaching that these oxa-borol compounds are volatile antimicrobial agents. In addition, these oxaborol compounds have not been used in agricultural applications.
[002] Thus, there remains a need to develop a new use of various volatile antimicrobial agents and / or combination with a regulator for the growth of volatile plants, in particular for agricultural applications. SUMMARY OF THE INVENTION
[003] The present invention relates to the use of a volatile antimicrobial compound against pathogens that affect meat, plants or parts of plants. The volatile antimicrobial compounds provided include certain oxaborol compounds, for example, benzoxaborols. Delivery systems are provided to take advantage of the volatile nature of these antimicrobial compounds. Combinations with a volatile plant growth regulator, for example, 1-methylcyclopropene, are also described.
em que q1 e q2 são, independentemente, 1,2 ou 3; q3 = 0, 1,2, 3 ou 4; M é hidrogênio, halogênio, -OCH3 ou -CH2-O-CH2-O-CH3; M1 é halogênio, -CH2OH ou -OCH3; X é O, S ou NR1c, em que R1c representa hidrogênio, alquila substituída ou alquila não substituída; R1, R1a, R1b, R2 e R5 são, independentemente, hidrogênio, OH, NH2, SH, CN, NO2, SO2, OSO2OH, OSO2NH2, cicloalquila substituída ou não substituída, ou hetero- cicloalquila substituída ou não substituída, arila substituída ou não substituída ou he- teroarila substituída ou não substituída; R* é arila substituída ou não substituída, arilalquila substituída ou não substituída, heteroarila substituída ou não substituída, heteroarilalquila substituída ou não substituída, ou vinila substituída ou não substituída; com a condição de que quando M é F, R* não seja um membro selecionado de: e com a condição de que quando M é Cl, R* não seja um membro selecionado de:  e com a condição de que quando M é hidrogênio, R* não seja um membro selecionado de: em que s - 1 ou 2; e R3 e R4são, independentemente, metila ou etila; e com a condição de que, quando M é OCH3, R* não seja um membro seleci-onado de: e com a condição de que, quando M1é F, R* não seja um membro selecionado e seus sais agricolamente aceitáveis.[004] In one aspect, a method of using a volatile antimicrobial compound against pathogens that affect meats, plants or parts of plants is provided. The method comprises contacting the pieces of meat, plants or parts of plants with an effective amount of the volatile antimicrobial compound that has a structure of formula (I), (II) or (III): where q1 and q2 are, independently, 1,2 or 3; q3 = 0, 1,2, 3 or 4; M is hydrogen, halogen, -OCH3 or -CH2-O-CH2-O-CH3; M1 is halogen, -CH2OH or -OCH3; X is O, S or NR1c, where R1c represents hydrogen, substituted alkyl or unsubstituted alkyl; R1, R1a, R1b, R2 and R5 are, independently, hydrogen, OH, NH2, SH, CN, NO2, SO2, OSO2OH, OSO2NH2, substituted or unsubstituted cycloalkyl, or substituted or unsubstituted heterocycloalkyl, substituted or not substituted aryl substituted or substituted or unsubstituted heteroaryl; R * is substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, or substituted or unsubstituted vinyl; with the proviso that when M is F, R * is not a selected member of : and with the proviso that when M is Cl, R * is not a selected member of: and with the proviso that when M is hydrogen, R * is not a selected member of : where s - 1 or 2; and R3 and R4 are, independently, methyl or ethyl; and with the proviso that, when M is OCH3, R * is not a selected member of: and with the proviso that when M1is F, R * is not a selected member and its agriculturally acceptable salts.
[005] In an embodiment of the aforementioned method, the pathogen is selected from the group consisting of Alternaria spp., Aspergillusspp., Botryospheria spp., Botrytis spp., Byssochlamys spp., Colletotrichum spp., Diplodia spp., Fusarium spp., Geotrichum spp., Lasiodiplodia spp., Monolinla spp., Mucor spp., Penicillium spp., Peziculaspp., Phomopsis spp., Phytophthora spp., Pythium spp., Rhizoctonia spp., Rhizopusspp., Sclerotinia spp. and Venturiaspp. In another embodiment, the pathogen is selected from the group consisting of Erwiniaspp., Pectobacterium spp., Pseudomonasspp., Ralstonia spp., Xanthomonasspp., Salmonellaspp., Escherichiaspp., Listeriaspp., Bacillusspp., Shigellaspp. and Staphylococcusspp. In another embodiment, the pathogen is selected from the group consisting of Candidaspp., Debaryomycesspp., Bacillusspp., Campylobacterspp., Clos-tridiumspp., Cryptosporidiumspp., Giardiaspp., Vibriospp. and Yersiniaspp. In another embodiment, the method comprises pre-harvest treatment or post-harvest treatment. In an additional embodiment, pre-harvest treatment is selected from the group consisting of seed treatment and transplant treatment. In another embodiment, the post-harvest treatment is selected from the group consisting of treatment during packaging in the field, treatment during palletization, treatment in the box, treatment during transport and treatment during storage and / or throughout the distribution network.
[006] In another embodiment, the plants or parts of plants comprise transgenic plants or parts of transgenic plants. In another embodiment, the plants or parts of plants are selected from the group consisting of corn, wheat, cotton, rice, soy and canola. In another embodiment, the plants or parts of plants are selected from the group consisting of fruits, vegetables, nurseries, peat and ornamental plants. In another embodiment, the fruits are selected from the group consisting of bananas, pineapples, citruses that include oranges, lemon, lime, grapefruit and other citruses, grapes, watermelon, cantaloupe, melon and other melons, apple, peach, pear, cherry , kiwi, mango, nectarine, guava, papaya, persimmon, pomegranate, avocado, fig and wild fruits that include strawberry, blueberry, raspberry, blackberry, currants and other types of wild fruits. In another embodiment, the vegetable is selected from the group consisting of tomatoes, potatoes, sweet potatoes, manioc, pepper, peppers, carrots, celery, pumpkin, eggplant, cabbage, cauliflower, broccoli, asparagus, mushrooms, onion, garlic, leeks and green beans. In an additional embodiment, the flower or part of the flower is selected from the group consisting of roses, carnations, orchids, geraniums, lilies or other ornamental flowers. In another embodiment, the meat is selected from the group of beef, bison, chicken, venison, goat, turkey, pork, sheep, fish, crustaceans, mollusks or dry-cured meat products.
[007] In one embodiment, the contact comprises the application of the volatile antimicrobial compound through modes selected from the group consisting of spraying, fogging, thermal or non-thermal nebulization, spraying, gas treatment and their combinations. In an additional embodiment, the gas treatment is selected from the group consisting of release from a sachet, release from a synthetic or natural film or fibrous material, and / or release from a coating or other materials. packaging, release from dust, release from a gas release generator, release using a cylinder of compressed or uncompressed gas, release from a droplet inside a box and combinations thereof. In another embodiment, the method further comprises the contact of meat, plants, parts of plants with a volatile plant growth regulator. In another embodiment, the volatile plant growth regulator is a cyclopropene compound. In another embodiment, the cyclopropene compound comprises 1-methylcyclopropene (1-MCP).
em que A e D juntamente com os átomos de carbono aos quais estão ligados formam um anel fundido de 5, 6 ou 7 membros que pode ser substituído por Ci-6- alquila, Ci-6-alcóxi, hidróxi, halogênio, nitro, nitrila, amino, amino substituído por um ou mais grupos Ci-6-alquila, carbóxi, acila, arilóxi, carbonamido, carbonamido substi-tuído por Ci-6-alquila, sulfonamido ou trifluormetila, ou o anel fundido pode ligar dois anéis oxaborol; X representa um grupo -CR7R8, em que R7 e R8 são cada um, independente-mente, hidrogênio, Ci-6-alquila, nitrila, nitro, arila, aralquila ou os símbolos R7 e R8 em juntamente com o átomo de carbono ao qual estão ligados formam um anel alicíclico; e R6 é hidrogênio, Ci-is-alquila, Ci-is-alquila substituída por Ci-6-alcóxi, C-i-6-al- quiltio, hidróxi, amino, amino substituído por Ci-is-alquila, carbóxi, arila, arilóxi, carbo- namido, (carbonamido substituído por Ci-6-alquila, arila ou aralquila), aralquila, arila, heteroarila, cicloalquila, Ci-i8-alquilenoamino, Ci-i8-alquilenoamino substituído porfe- nila, Ci-6-alcóxi ou Ci-s-alquiltio, carbonilalquilenoamino ou um radical de fórmula (V): em que A, D e X são como aqui definidos antes, exceto para boronoftalida; e seus sais agricolamente aceitáveis.[008] In another aspect, a method of using a volatile antimicrobial compound against pathogens that affect meat, plants or parts of plants is provided. The method consists of contacting the pieces of meat, plants or parts of plants with an effective amount of the volatile antimicrobial compound of formula (IV): where A and D together with the carbon atoms to which they are attached form a fused 5-, 6- or 7-membered ring that can be replaced by C1-6 alkyl, C1-6 alkoxy, hydroxy, halogen, nitro, nitrile , amino, amino substituted by one or more C1-6-alkyl, carboxy, acyl, aryloxy, carbonamido, carbonamido substituted by C1-6-alkyl, sulfonamido or trifluoromethyl, or the fused ring can link two oxaborol rings; X represents a -CR7R8 group, where R7 and R8 are each, independently, hydrogen, C1-6-alkyl, nitrile, nitro, aryl, aralkyl or the symbols R7 and R8 together with the carbon atom to which they are linked form an alicyclic ring; and R6 is hydrogen, Ci-is-alkyl, Ci-is-alkyl substituted by Ci-6-alkoxy, Ci-6-alkylthio, hydroxy, amino, amino substituted by Ci-is-alkyl, carboxy, aryl, aryloxy , carbonamide, (carbonamido substituted by C1-6-alkyl, aryl or aralkyl), aralkyl, aryl, heteroaryl, cycloalkyl, C1-8 alkyleneamino, C1-8 alkyleneamino substituted by phenyl, C1-6 alkoxy or C1- s -alkylthio, carbonylalkyleneamino or a radical of formula (V): where A, D and X are as defined herein before, except for boronophthalide; and its agriculturally acceptable salts.
[009] In an embodiment of the method provided, the pathogen is selected from the group consisting of Alternariaspp., Aspergillusspp., Botryospheria spp., Botrytis spp., Byssochlamys spp., Colletotrichum spp., Diplodia spp., Fu-sarium spp., Geotrichum spp., Lasiodiplodia spp., Monolinia spp., Mucor spp., Penicillium spp., Peziculaspp., Phomopsis spp., Phytophthora spp., Pythium spp., Rhizoptosia spp., Rhizopus spp., Sclerotinia spp. and Venturiaspp. In another embodiment, the pathogen is selected from the group consisting of Erwiniaspp., Pectobacterium spp., Pseudomonasspp., Ralstonia spp., Xanthomonasspp., Salmo-nellaspp., Escherichiaspp., Listeriaspp., Bacillusspp., Shigellaspp. and Staphylococ-cusspp. In another embodiment, the pathogen is selected from the group consisting of Candidaspp., Debaryomycesspp., Bacillusspp., Campylobac-terspp., Clostridiumspp., Cryptosporidiumspp., Giardiaspp., Vibriospp. and Yersinia spp. In another embodiment, the method comprises pre-harvest treatment or post-harvest treatment. In an additional embodiment, the pre-harvest treatment is selected from the group consisting of seed treatment and transplant treatment. In another embodiment, post-harvest treatment is selected from the group consisting of treatment during packaging in the field, treatment during palletization, treatment in the box, treatment during transport and treatment during storage and / or throughout the distribution network.
[010] In another embodiment, the plants or parts of plants comprise transgenic plants or parts of transgenic plants. In another embodiment, the plants or parts of plants are selected from the group consisting of corn, wheat, cotton, rice, soy and canola. In another embodiment, the plants or parts of plants are selected from the group consisting of fruits, vegetables, nurseries, peat and ornamental plants. In an additional embodiment, the fruits are selected from the group consisting of bananas, pineapples, citruses that include oranges, lemon, lime, grapefruit and other citruses, grapes, watermelon, cantaloupe, melon and other melons, apple, peach , pear, cherry, kiwi, mango, nectarine, guava, papaya, persimmon, pomegranate, avocado, fig and wild fruits including strawberry, blueberry, raspberry, blackberry, blackberry, currants and other types of wild fruits. In another embodiment, the vegetable is selected from the group consisting of tomatoes, potatoes, sweet potatoes, manioc, pepper, peppers, carrots, celery, pumpkin, eggplant, cabbage, cauliflower, broccoli, asparagus, mushrooms, onion , garlic, leeks and green beans. In an additional embodiment, the flower or part of the flower is selected from the group consisting of roses, carnations, orchids, geraniums, lilies or other ornamental flowers. In another embodiment, the meat is selected from the group of beef, bison, chicken, venison, goat, turkey, pork, sheep, fish, crustaceans, mollusks or dry-cured meat products.
[011] In one embodiment, the contact comprises the application of the volatile antimicrobial compound through modes selected from the group consisting of spraying, fogging, thermal or non-thermal nebulization, spraying, gas treatment and their combinations. In an additional embodiment, the gas treatment is selected from the group consisting of release from a sachet, release from a synthetic or natural film or fibrous material, and / or release from a coating or other materials. packaging, release from dust, release from a gas release generator, release using a cylinder of compressed or uncompressed gas, release from a droplet inside a box and combinations thereof. In another embodiment, the method further comprises the contact of meat, plants, parts of plants with a volatile plant growth regulator. In another embodiment, the volatile plant growth regulator is a cyclopropene compound. In another embodiment, the cyclopropene compound comprises 1-methylcyclopropene (1-MCP).
em que cada R é, independentemente, hidrogênio, alquila, alqueno, alquino, haloalquila, haloalqueno, haloalquino, alcóxi, alquenóxi, haloalcóxi, arila, heteroarila, arilalquila, arilalqueno, arilalquino, heteroarilalquila, heteroarilalqueno, heteroarilal- quino, halogênio, hidroxila, nitrila, amina, éster, ácido carboxílico, cetona, álcool, su- feto, sulfóxido, sulfona, sulfoximina, sulfilimina, sulfonamida, sulfato, sulfonato, nitro- alquila, amida, oxima, imina, hidroxilamina, hidrazina, hidrazona, carbamato, tiocarba- mato, ureia, tioureia, carbonato, arilóxi ou heteroarilóxi; n = 1,2, 3 ou 4; B é boro; X = (CR2)m, em que m = 1,2, 3 ou 4; Y é alquila, alqueno, alquino, haloalquila, haloalqueno, haloalquina, alcóxi, alquenóxi, haloalcóxi, arila, heteroarila, arilalquila, arilalqueno, arilalquino, heteroari- lalquila, heteroarilalqueno, heteroarilalquino, hidroxila, nitrila, amina, éster, ácido carboxílico, cetona, álcool, sufeto, sulfóxido, sulfona, sulfoximina, sulfilimina, sulfona- mida, sulfato, sulfonato, nitroalquila, amida, oxima, imina, hidroxilamina, hidrazina, hi- drazona, carbamato, tiocarbamato, ureia, tioureia, carbonato, arilóxi ou heteroarilóxi; com a condição de que R não seja arilóxi ou heteroarilóxi, quando Y é hidro-xila; e seus sais agricolamente aceitáveis.[012] In another aspect, a method of using a volatile antimicrobial compound against pathogens that affect meat, plants or parts of plants is provided. The method consists of contacting the pieces of meat, plants or parts of plants with an effective amount of the volatile antimicrobial compound of formula (VI): wherein each R is independently hydrogen, alkyl, alkene, alkaline, haloalkyl, haloalkene, haloalkine, alkoxy, alkoxy, haloalkoxy, aryl, heteroaryl, arylalkyl, arylalkylene, arylalkyl, heteroarylalkyl, heteroarylalkyl, heteroarylalkyl, heteroarylalkyl, heteroarylalkyl, heteroarylalkyl, heteroarylalkyl nitrile, amine, ester, carboxylic acid, ketone, alcohol, sulfide, sulfoxide, sulfone, sulfoximine, sulfylimine, sulfonamide, sulfate, sulfonate, nitro-alkyl, amide, oxime, imine, hydroxylamine, hydrazine, hydrazone, carbamate, thiocarba - bush, urea, thiourea, carbonate, aryloxy or heteroaryloxy; n = 1,2, 3 or 4; B is boron; X = (CR2) m, where m = 1,2, 3 or 4; Y is alkyl, alkene, alkaline, haloalkyl, haloalkene, haloalkine, alkoxy, alkenoxy, haloalkoxy, aryl, heteroaryl, arylalkyl, arylalkene, arylalkyl, heteroarylalkyl, heteroarylalkene, heteroaryl, acid, heteroaryl, alkaline, heteroaryl, alkaline, heteroaryl , alcohol, sulfide, sulfoxide, sulfone, sulfoximine, sulfylimine, sulfonamide, sulfate, sulfonate, nitroalkyl, amide, oxime, imine, hydroxylamine, hydrazine, hydrazine, carbamate, thiocarbamate, urea, thiourea, carbonate, aryloxy or heteroaryl ; with the proviso that R is not aryloxy or heteroaryloxy, when Y is hydroxyl; and its agriculturally acceptable salts.
em que W = (CH2) q, em que q é 1,2 ou 3.[013] In one embodiment, the volatile antimicrobial compound has a structure of formula (VII): where W = (CH2) q, where q is 1,2 or 3.
[014] In another embodiment, the volatile antimicrobial compound has a structure of
[015] In an embodiment of the method provided, the pathogen is selected from the group consisting of Alternaria spp., Aspergillusspp., Botryospheria spp., Botrytis spp., Byssochlamys spp., Colletotrichum spp., Diplodia spp. , Fu-sarium spp., Geotrichum spp., Lasiodiplodia spp., Monolinia spp., Mucor spp., Penicillium spp., Peziculaspp., Phomopsis spp., Phytophthora spp., Pythium spp., Rhizocto- nia spp., Rhizopus spp., Sclerotinia spp. and Venturiaspp. In another embodiment, the pathogen is selected from the group consisting of Erwiniaspp., Pectobacterium spp., Pseudomonasspp., Ralstonia spp., Xanthomonasspp., Salmo-nellaspp., Escherichiaspp., Listeriaspp., Bacillusspp., Shigellaspp. and Staphylococ-cusspp. In another embodiment, the pathogen is selected from the group consisting of Candidaspp., Debaryomycesspp., Bacillusspp., Campylobac-ter spp., Clostridiumspp., Cryptosporidiumspp., Giardiaspp., Vibriospp. and Yersinia spp. In another embodiment, the method comprises pre-harvest treatment or post-harvest treatment. In another embodiment, pre-harvest treatment is selected from the group consisting of seed treatment and transplant treatment. In another embodiment, the post-harvest treatment is selected from the group consisting of treatment during packaging in the field, treatment during palletization, treatment in the box, treatment during transport and treatment during storage and / or throughout the distribution network.
[016] In another embodiment, the plants or parts of plants comprise transgenic plants or parts of transgenic plants. In another embodiment, the plants or parts of plants are selected from the group consisting of corn, wheat, cotton, rice, soy and canola. In another embodiment, the plants or parts of plants are selected from the group consisting of fruits, vegetables, nurseries, peat and ornamental plants. In another embodiment, the fruits are selected from the group consisting of bananas, pineapples, citruses that include oranges, lemon, lime, grapefruit and other citruses, grapes, watermelon, cantaloupe, melon and other melons, apple, peach, pear, cherry , kiwi, mango, nectarine, guava, papaya, persimmon, pomegranate, avocado, fig and wild fruits that include strawberry, blueberry, raspberry, blackberry, blackberry, currants and other types of wild fruits. In another embodiment, the vegetable is selected from the group consisting of tomatoes, potatoes, sweet potatoes, manioc, pepper, peppers, carrots, celery, pumpkin, eggplant, cabbage, cauliflower, broccoli, asparagus, mushrooms, onions, garlic, leeks and green beans. In an additional embodiment, the flower or part of the flower is selected from the group consisting of roses, carnations, orchids, geraniums, lilies or other ornamental flowers. In another embodiment, the meat is selected from the group of beef, bison, chicken, venison, goat, turkey, pork, sheep, fish, crustaceans, mollusks or dry-cured meat products.
[017] In one embodiment, the contact comprises the application of the volatile antimicrobial compound through modes selected from the group consisting of spraying, fogging, thermal or non-thermal nebulization, spraying, gas treatment and their combinations. In an additional embodiment, the gas treatment is selected from the group consisting of release from a sachet, release from a synthetic or natural film or fibrous material, and / or release from a coating or other materials. packaging, release from dust, release from a gas release generator, release using a cylinder of compressed or uncompressed gas, release from a droplet inside a box and combinations thereof. In another embodiment, the method further comprises the contact of meat, plants, parts of plants with a volatile plant growth regulator. In another embodiment, the volatile plant growth regulator is a cyclopropene compound. In another embodiment, the cyclopropene compound comprises 1-methylcyclopropene (1-MCP).
em que Ra é CN, C(O)NR9R10 ou C(O)OR11, em que R11 é hidrogênio, alquila substituída ou alquila não substituída, Xé N, CH e CRb; Rb é halogênio, alquila substituída ou não substituída, C(O)R12, C(O)OR12, OR12, NR12R13, em que R9, R10, R12e R13são, independentemente, hidrogênio, alquila substituída ou não substituída, heteroalquila substituída ou não substituída, cicloal- quila substituída ou não substituída, heterocicloalquila substituída ou não substituída, arila substituída ou não substituída, ou heteroarila substituída ou não substituída; com a condição de que R9 e R10, juntamente com os átomos aos quais estão ligados, sejam opcionalmente combinados para formar um anel heterocicloal-quila substituído ou não substituído de a 4 a 8 membros; e com a condição de que R12 e R13, juntamente com os átomos aos quais estão ligados, sejam opcionalmente combinados para formar um anel heterocicloal-quila substituído ou não substituído de a 4 a 8 membros; e seus sais agricolamente aceitáveis.[018] In another aspect, a method of using a volatile antimicrobial compound against pathogens that affect meat, plants or parts of plants is provided. The method consists of contacting the pieces of meat, plants or parts of plants with an effective amount of the volatile antimicrobial compound of formula (VIII): where Ra is CN, C (O) NR9R10 or C (O) OR11, where R11 is hydrogen, substituted alkyl or unsubstituted alkyl, X is N, CH and CRb; Rb is halogen, substituted or unsubstituted alkyl, C (O) R12, C (O) OR12, OR12, NR12R13, where R9, R10, R12 and R13 are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl , substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; with the proviso that R9 and R10, together with the atoms to which they are attached, are optionally combined to form a 4- to 8-membered substituted or unsubstituted heterocycloalkyl ring; and with the proviso that R12 and R13, together with the atoms to which they are attached, are optionally combined to form a 4- to 8-membered substituted or unsubstituted heterocycloalkyl ring; and its agriculturally acceptable salts.
[019] In one embodiment of the method provided, the pathogen is selected from the group consisting of Alternaria spp., Aspergillusspp., Botryospheria spp., Botrytis spp., Byssochlamys spp., Colletotrichum spp., Diplodia spp. , Fu-sarium spp., Geotrichum spp., Lasiodiplodia spp., Monolinia spp., Mucor spp., Penicillium spp., Pezicula spp., Phomopsis spp., Phytophthora spp., Pythium spp., Rhizocto- nia spp. , Rhizopus spp., Sclerotinia spp. and Venturiaspp. In another embodiment, the pathogen is selected from the group consisting of Erwiniaspp., Pectobacterium spp., Pseudomonasspp., Ralstonia spp., Xanthomonasspp., Salmo-nellaspp., Escherichiaspp., Listeriaspp., Bacillusspp., Shigellaspp. and Staphylococ-cusspp. In another embodiment, the pathogen is selected from the group consisting of Candidaspp., Debaryomycesspp., Bacillusspp., Campylobac-terspp., Clostridiumspp., Cryptosporidiumspp., Giardiaspp., Vibriospp. and Yersinia spp. In another embodiment, the method comprises pre-harvest treatment or post-harvest treatment. In an additional embodiment, the pre-harvest treatment is selected from the group consisting of seed treatment and transplant treatment. In another embodiment, the post-harvest treatment is selected from the group consisting of treatment during packaging in the field, treatment during palletization, treatment in the box, treatment during transport and treatment during storage and / or throughout the distribution network.
[020] In another embodiment, the plants or parts of plants comprise transgenic plants or parts of transgenic plants. In another embodiment, the plants or parts of plants are selected from the group consisting of corn, wheat, cotton, rice, soy and canola. In another embodiment, the plants or parts of plants are selected from the group consisting of bananas, pineapples, citruses that include oranges, lemon, lime, grapefruit and other citruses, grapes, watermelon, cantaloupe, melon and other melons , apple, peach, pear, cherry, kiwi, mango, nectarine, guava, papaya, persimmon, pomegranate, avocado, fig and berries including strawberry, blueberry, raspberry, blackberry, blackberry, currants and other types of berries. In another embodiment, the vegetable is selected from the group consisting of tomatoes, potatoes, sweet potatoes, manioc, pepper, peppers, carrots, celery, pumpkin, eggplant, cabbage, cauliflower, broccoli, asparagus, mushrooms, onions, garlic, leeks and green beans. In an additional embodiment, the flower or part of the flower is selected from the group consisting of roses, carnations, orchids, geraniums, lilies or other ornamental flowers. In another embodiment, the meat is selected from the group of beef, bison, chicken, venison, goat, turkey, pork, sheep, fish, crustaceans, mollusks or dry-cured meat products.
[021] In one embodiment, the contact comprises the application of the volatile antimicrobial compound through modes selected from the group consisting of spraying, fogging, thermal or non-thermal nebulization, spraying, gas treatment and their combinations. In an additional embodiment, gas treatment is selected from the group consisting of release from a sachet, release from a synthetic or natural film, release from coating or other packaging materials, release from powder, release from a gas release generator, release using a cylinder of compressed or uncompressed gas, release from a droplet inside a box and its combinations. In another embodiment, the method further comprises the contact of meat, plants, parts of plants with a volatile plant growth regulator. In another embodiment, the volatile plant growth regulator is a cyclopropene compound. In another embodiment, the cyclopropene compound comprises 1-methylcyclopropene (1-MCP). CONCISE DESCRIPTION OF THE DRAWINGS
[022] Figure 1 shows the chemical structure of an exemplary compound A of the invention.
[023] Figure 2 shows the chemical structure of an exemplary compound B of the invention.
[024] Figure 3 shows fourteen compounds tested in Example 2 and their respective minimum inhibitory concentrations (MICs).
[025] Figure 4 shows representative photographs of exemplary results of inhibition in vivo using Compound A, where 0.04 mg of Compound A shows 100% inhibition and 0.0024 mg of Compound A shows no inhibition.
[026] Figure 5 shows representative photographs of exemplary in vivo inhibition of Botrytis cinerea from an application of volatile compound 10 after a three-day treatment at 21 ° C, followed by an additional two days at 21 ° C. DETAILED DESCRIPTION OF THE INVENTION
[027] Unless otherwise specified, the following terms used in this application, including the specification and claims, have the definitions given below. It should be noted that, as used in the specification and the appended claims, the singular forms "um", "uma" and "o", "a" include plural referents, unless the context clearly indicates otherwise. Definition of standard chemistry terms can be found in reference works, including Carey and Sundberg, Advanced Organic Chemistry, 4th ed., Vols. A (2000) and B (2001), Plenum Press, New York, NI
[028] As used herein, the term "unit" refers to a specific segment or functional group of a molecule. Chemical moieties are often recognized chemical entities embedded in or attached to a molecule.
[029] As used herein, the terms "heteroatom" and "hetero" refer to atoms other than carbon (C) and hydrogen (H). Examples of heteroatoms include oxygen (O), nitrogen (N), sulfur (S), silicon (Si), germanium (Ge), aluminum (Al) and boron (B).
[030] As used herein, the terms "halo" and "halogen" are interchangeable and refer to fluorine (-F), chlorine (-CI), bromine (-Br) and iodine (-I).
[031] As used herein, the term "alkyl" refers to a substituted or unsubstituted hydrocarbon group and may include linear, branched, cyclic, saturated and / or unsaturated characteristics. Although the alkyl portion may be an "unsaturated alkyl" portion, which means that it contains at least one alkene or alkane; typically, the alkyl moiety is a "saturated alkyl" group, meaning that it does not contain any alkene or alkaline moieties. Likewise, although the alkyl moiety may be a cyclic moiety, typically the alkyl moiety is a non-cyclic group. Thus, in some embodiments, "alkyl" refers to an optionally substituted straight chain or optionally substituted saturated hydrocarbon monoradical that has from about one to about thirty carbon atoms in some embodiments, from about one to about fifteen carbon atoms in some embodiments, and about one to about six carbon atoms in additional embodiments. Examples of saturated alkyl radicals include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, 2-methyl-1-propyl, 2-methyl-2-propyl, 2-methyl-1-butyl, 3-methyl- 1 -butyl, 2-methyl-3-butyl, 2,2-dimethyl-1-propyl, 2-methyl-1-pentyl, 3-methyl-1-pentyl, 4-methyl-1-pentyl, 2-methyl-2 -pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 2,2-dimethyl-1-butyl, 3,3-dimethyl-1-butyl, 2-ethyl- 1-butyl, butyl, isobutyl , sec-butyl, t-butyl, n-pentyl, isopentyl, neopentyl and n-hexyl, and longer alkyl groups, such as heptyl and octyl. It should be noted that whenever it appears here, a numerical range such as "1 to 6" refers to each integer in the given range, for example, "1 to 6 carbon atoms" or "Ci-β" or " Ci-Ce "means that the alkyl group may consist of 1 carbon atom, two carbon atoms, three carbon atoms, four carbon atoms, five carbon atoms and / or six carbon atoms, although this definition also covers the occurrence of the term "alkyl" where no numerical range is designated.
[032] As used herein, the term "substituted alkyl" refers to an alkyl group, as defined herein, in which one or more (up to about five, preferably up to about three) hydrogen atoms are substituted by a substituent independently selected from the substituent group as defined herein.
[033] As used herein, the terms "substituents" and "substituted" refer to groups that can be used to replace another group in a molecule. Such groups are known to those skilled in the chemical art and may include, without limitation, one or more of the following independently selected groups, or subsets thereof: halogen, -CN, -OH, -NO2, -N3, = 0 , = S, = NH, -SO2, -NH2, -COOH, -S (O2), nitroalkyl, amino, including mono- and disubstituted amino groups, cyanate, isocyanate, thiocyanate, isothiocyanate, guanidinyl, 0-carbamyl, N-carbamyl , tiocarbamila, urila, isourila, tiourila, isothiourila, mercapto, sulpila, sulphinyl, sulphonyl, sulphonamidyl, phosphonyl, phosphatidylcholine, phosphoramidyl, dialkylamine, diarylamine, diarylalkylamino and the compounds of these protected. The protecting groups that can form the protected compounds of the above substituents are known to those skilled in the art and can be found in references such as Greene and Wuts, Protective Groups in Organic Synthesis, 3rd ed., John Wiley & Sons, New York, Nl (1999), and Kocienski, Protective Groups, Thieme Verlag, New York, Nl (1994), which are incorporated herein in full as a reference.
[034] As used herein, the term "alkoxy" refers to -O-alkyl, where alkyl is as defined herein. In one embodiment, alkoxy groups include, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, sec-butoxy, n-pentoxy, n-hexoxy, 1,2-dimethylbutoxy and the like. The alkoxy can be unsubstituted or substituted.
[035] As used herein, the terms "cyclic" and "ring with limbs" refer to any cyclic structure, including fused or unfused alicyclic, heterocyclic, aromatic, heteroaromatic and polycyclic ring systems, as herein described. The term "with limbs" is intended to indicate the number of atoms in the skeleton that makes up the ring. Thus, for example, pyridine, pyran and pyrimidine are six-membered rings, and pyrrole, tetrahydrofuran and thiophene are five-membered rings.
[036] As used herein, the term "aromatic" refers to a cyclic or polycyclic portion that has an unsaturated conjugated electron system (4n + 2) π (where n is a positive integer) , sometimes referred to as a delocalized π electron system.
[037] As used herein, the term "aryl" refers to an aromatic cyclic hydrocarbon monoradical optionally substituted from six to about twenty atoms in the ring, preferably from six to about ten carbon atoms and includes aromatic rings fused (or condensed) and unfused. A fused aromatic ring radical contains two to four fused rings, where the bonding ring is an aromatic ring and the other individual rings within the fused ring can be cycloalkyl, cycloalkenyl, cycloalkyl, heterocycloalkyl, heterocycloalkenyl, heterocycloalkyl, aromatic ring , heteroaromatic ring or any combination thereof. A non-limiting example of a single aryl ring group includes phenyl; a fused aryl ring group includes naphthyl, anthryl, azulenyl; and an unfused biaryl group includes biphenyl.
[038] As used herein, the term "substituted aryl" refers to an aryl group, as defined herein, in which one or more (up to about five, preferably up to about three) hydrogen atoms are replaced by a substituent independently selected from the group defined here (unless otherwise limited by the definition for the aryl substituent).
[039] As used herein, the term "heteroaryl" refers to an optionally substituted aromatic cyclic monoradical, containing from about five to about twenty atoms in the skeleton ring, preferably from five to about ten atoms in the ring, and includes fused (or condensed) and unfused aromatic rings that have one or more (one to ten, preferably about one to four) atoms in the ring selected from an atom other than carbon (i.e., one heteroatom), such as, for example, oxygen, nitrogen, sulfur, selenium, phosphorus or combinations thereof. The term heteroaryl includes optionally substituted fused and unfused heteroaryl radicals having at least one heteroatom. A fused heteroaryl radical can contain two to four fused rings, where the linking ring is a heteroaromatic ring and the other individual rings within the fused ring system can be alicyclic, heterocyclic, aromatic, heteroaromatic or any combination thereof. The term heteroaryl also includes fused or unfused heteroaryls that have five to about twelve atoms in the ring skeleton, as well as those that have five to about ten atoms in the ring skeleton. Examples of heteroaryl groups include, but are not limited to, acridinyl, benzo [1,3] dioxol, benzimidazolyl, benzindazolyl, benzoisoxazolyl, benzoquisazolyl, benzofuranyl, benzofurazanyl, benzopyran, benzothiadiazolyl, benzothiazolyl, benzothiazolyl, benzo [b] tien benzoxazolyl, carbazolyl, carbolinyl, chromenyl, cinoliπila, furanila, furazanila, furopiridinyl, furila, imidazolyl, indazolyl, indolila, indolidiπila, iπdoliziπila, isobeπzofuranila, isoiπdila, isol, nazinol, isin, isol, nazinin, iso oxazolyl, phenoxazinyl, phenothiazinyl, phenazinyl, phenoxathione, thiantrenyl, phenatridinyl, phenatrolinyl, fta- lazinyl, pteridinyl, purinyl, puteridinyl, pyrazyl, pyrazolyl, pyridyl, pyridinyl, pyridinyl, pyridinyl, pyrazine quinoxalinyl, tetrazolyl, thiadiazolyl, thiazolyl, thienyl, triazinyl, (1,2,3) - and (1,2,4) - triazolyl and the like, and their oxides, where appropriate, such as, for example, pyridyl-N-oxide.
[040] As used herein, the term "substituted heteroaryl" refers to a heteroaryl group, as defined herein, in which one or more (up to about five, preferably up to about three) hydrogen atoms are replaced by a substitute independently selected from the group defined here.
[041] As used herein, the term "leaving group" refers to a group with the meaning conventionally associated with it in synthetic organic chemistry, that is, an atom or group displaceable under substitution reaction conditions. Examples of leaving groups include, but are not limited to, halogen, alkane or arylsulfonyloxy, such as methanesulfonyloxy, ethanesulfonyloxy, thiomethyl, benzenesulfonyloxy, tosyloxy and thienyloxy, dialophosphinoyloxy, optionally substituted, isopropyloxy and similar, isopropyloxy. In some embodiments, an leaving group can be HC (O) -COOH or RC (O) -COOH, where R is C 1 -C 6 alkyl or substituted C 1 -C 6 alkyl.
[042] The compounds of the invention, as described herein, can be synthesized using conventional synthetic techniques known to those of skill in the art or by methods known in the art, in combination with the methods described herein. The starting materials used for the synthesis of the compounds of the invention as described herein, can be obtained from commercial sources, such as Aldrich Chemical Co. (Milwaukee, Wisconsin), Sigma Chemical Co. (St. Louis, Missouri), or can be synthesized. The compounds described herein, and other related compounds having different substituents can be synthesized using techniques and materials known to those of skill in the art, as described, for example, in March, Advanced Organic Chemistry, 4th ed. (1992), John Wlley & Sons, New York, NI; Carey and Sundberg, Advanced Organic Chemistry, 4th ed., Vols. A (2000) and B (2001), Plenum Press, New York, NI, and Greene and Wuts, Protective Groups in Organic Synthesis, 3aed. (1999), John Wiley & Sons, New York, Nl (which are incorporated herein in full by reference). General methods for preparing the compound as described herein can be derived from reactions known in the field, and the reactions can be modified by using appropriate reagents and conditions, as would be recognized by the expert, for the introduction of the various portions found in the formulas as provided here. For example, the compounds described herein can be modified using various electrophiles or nucleophiles to form new functional or substituent groups.
em que q1 e q2 são, independentemente, 1,2 ou 3; q3 = 0, 1,2, 3 ou 4; M é hidrogênio, halogênio, -OCH3 ou -CH2-O-CH2-O-CH3; M1 é halogênio, -CH2OH ou -OCH3; X é O, S ou NR1c, em que R1c representa hidrogênio, alquila substituída ou alquila não substituída; R1, R1a, R1b, R2 e R5 são, independentemente, hidrogênio, OH, NH2, SH, CN, Nθ2, SO2, OSO2OH, OSO2NH2, cicloalquila substituída ou não substituída, ou hetero- cicloalquila substituída ou não substituída, arila substituída ou não substituída, ou he- teroarila substituída ou não substituída; R* é arila substituída ou não substituída, arilalquila substituída ou não substituída, heteroarila substituída ou não substituída, heteroarilalquila substituída ou não substituída, ou vinila substituída ou não substituída; com a condição de que quando M é F, R* não seja um membro selecionado de: e com a condição de que quando M é Cl, R* não seja um membro selecionado de: e com a condição de que quando M é hidrogênio, R* não seja um membro selecionado de:  em que s - 1 ou2; e R3e R4são, independentemente, metila ou etila; e com a condição de que quando M é OCH3, R* não seja um membro seleci-onado de: e com a condição de que quando M1é F, R* não seja um membro selecionado de:  e seus sais agricolamente aceitáveis.[043] In some embodiments, the volatile antimicrobial compound of the invention has a structure of formula (I), (II) or (III): where q1 and q2 are, independently, 1,2 or 3; q3 = 0, 1,2, 3 or 4; M is hydrogen, halogen, -OCH3 or -CH2-O-CH2-O-CH3; M1 is halogen, -CH2OH or -OCH3; X is O, S or NR1c, where R1c represents hydrogen, substituted alkyl or unsubstituted alkyl; R1, R1a, R1b, R2 and R5 are independently hydrogen, OH, NH2, SH, CN, Nθ2, SO2, OSO2OH, OSO2NH2, substituted or unsubstituted cycloalkyl, or substituted or unsubstituted heterocycloalkyl, substituted or not substituted aryl substituted, or substituted or unsubstituted heteroaryl; R * is substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, or substituted or unsubstituted vinyl; with the proviso that when M is F, R * is not a selected member of: and with the proviso that when M is Cl, R * is not a selected member of: and with the proviso that when M is hydrogen, R * is not a selected member of: where s - 1 or 2; and R3 and R4 are, independently, methyl or ethyl; and with the proviso that when M is OCH3, R * is not a selected member of: and with the proviso that when M1 is F, R * is not a selected member of: and its agriculturally acceptable salts.
em que X é um membro selecionado de CH=CH, N=CH, NR14, O e S; em que R14 é um membro selecionado de H, alquila substituída ou não subs-tituída, arila substituída ou não substituída e arilal quila substituída ou não substituída; Y é um membro selecionado de CH e N; R17 e R18 são membros independentemente selecionados de H, alquila substituída ou não substituída, arila substituída ou não substituída, arilalquila substituída ou não substituída, (CH2)vOH, (CH2)wNR15R16, CO2H, CO2-alquila, CONH2, S-alquila, S-arila, SO-alquila, SO-arila, SO2-alquila, SO2-arila, SO2H, SCF2, CN, halogênio, CF3 e NO2; em que R15 e R16 são membros independentemente selecionados de hidrogênio, alquila substituída ou não substituída e alcanoíla substituída ou não substituída; v = 1, 2 ou 3; e w = 0, 1, 2 ou 3.[044] In one embodiment, R * has a selected structure where X is a selected member of CH = CH, N = CH, NR14, O and S; wherein R14 is a selected member of H, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, and substituted or unsubstituted arylalkyl; Y is a selected member of CH and N; R17 and R18 are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, (CH2) vOH, (CH2) wNR15R16, CO2H, CO2-alkyl, CONH2, S-alkyl, S-aryl, SO-alkyl, SO-aryl, SO2-alkyl, SO2-aryl, SO2H, SCF2, CN, halogen, CF3 and NO2; wherein R15 and R16 are independently selected members of hydrogen, substituted or unsubstituted alkyl and substituted or unsubstituted alkanoyl; v = 1, 2 or 3; ew = 0, 1, 2 or 3.
em que R17, R18RIΘ R2O θ R2Isθ0selecionados independentemente de H, alquila substituída ou não substituída, arila substituída ou não substituída, arilalquila substituída ou não substituída, alquilóxi substituído ou não substituído, arilóxi substi-tuído ou não substituído, oxazolidin-2-ila substituída ou não substituída, (CH2)tOH, CO2H, CO2-alquila, CONH2, CONH-alquila, CON(alquila)2, OH, SH, S-alquila, S-arila, SO-alquila, SO-arila, SO2-alquila, SO2-arila, SO2H, SCF3, CN, halogênio, CF3, NO2, (CH2)UNR22R23, SO2NH2, OCH2CH2NH2, OCH2CH2NH-alquila e OCH2CH2N(alquila)2; em que t = 1,2 ou 3; u = 0, 1 ou 2; R22 e R23 são independentemente selecionados de H, alquila substituída ou não substituída e alcanoíla substituída ou não substituída.[045] In another embodiment, R * has the following structure: where R17, R18RIΘ R2O θ R2Isθ0selected independently from H, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted aryloxy, substituted oxazolidin-2-yl or unsubstituted, (CH2) tOH, CO2H, CO2-alkyl, CONH2, CONH-alkyl, CON (alkyl) 2, OH, SH, S-alkyl, S-aryl, SO-alkyl, SO-aryl, SO2-alkyl , SO2-aryl, SO2H, SCF3, CN, halogen, CF3, NO2, (CH2) UNR22R23, SO2NH2, OCH2CH2NH2, OCH2CH2NH-alkyl and OCH2CH2N (alkyl) 2; where t = 1.2 or 3; u = 0, 1 or 2; R22 and R23 are independently selected from H, substituted or unsubstituted alkyl and substituted or unsubstituted alkanoyl.
em que R17, R18, R19 R20 e R21 são independentemente selecionados de H, alquila substituída ou não substituída, arila substituída ou não substituída, arilalquila substituída ou não substituída, alquilóxi substituído ou não substituído, arilóxi substi-tuído ou não substituído, oxazolidin-2-ila substituída ou não substituída, (CH2)tOH, CO2H, Cθ2-alquila, CONH2, CONH-alquila, CON(alquila)2, OH, SH, S-alquila, S-arila, SO-alquila, SO-arila, Sθ2-alquila, Sθ2-arila, SO2H, SCF3, CN, halogênio, CF3, NO2, (CH2)UNR22R23, SO2NH2, OCH2CH2NH2, OCH2CH2NH-alquila e OCH2CH2N(alquila)2; em que t = 1,2 ou 3; u = 0, 1 ou 2; R22 e R23 são independentemente selecionados de H, alquila substituída ou não substituída e alcanoíla substituída ou não substituída. R22 e R23 são independentemente selecionados de H, alquila substituída ou não substituída e alcanoíla substituída ou não substituída; R24 e R25 são independentemente selecionados de H, alquila substituída ou não substituída, arila substituída ou não substituída, arilalquila substituída ou não substituída, alquilóxi substituído ou não substituído, arilóxi substituído ou não substi-tuído, oxazolidin-2-ila substituída ou não substituída, (CH2)tOH, CO2H, CO2-alquila, CONH2, CONH-alquila, CON(alquila)2, OH, SH, S-alquila, S-arila, SO-alquila, SO- arila, SO2-alquila, SO2-arila, SO3H, SCF3, CN, halogênio, CF3, NO2, (CH2)uNR22R23, SO2NH2, OCH2CH2NH2, OCH2CH2NH-alquila e OCH2CH2N(alquila)2; Z= 1, 2, 3, 4, 5 ou 6.[046] In another embodiment, R * has the following structure: where R17, R18, R19 R20 and R21 are independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted aryloxy, oxazolidin- 2-yl substituted or unsubstituted, (CH2) tOH, CO2H, Cθ2-alkyl, CONH2, CONH-alkyl, CON (alkyl) 2, OH, SH, S-alkyl, S-aryl, SO-alkyl, SO-aryl , Sθ2-alkyl, Sθ2-aryl, SO2H, SCF3, CN, halogen, CF3, NO2, (CH2) UNR22R23, SO2NH2, OCH2CH2NH2, OCH2CH2NH-alkyl and OCH2CH2N (alkyl) 2; where t = 1.2 or 3; u = 0, 1 or 2; R22 and R23 are independently selected from H, substituted or unsubstituted alkyl and substituted or unsubstituted alkanoyl. R22 and R23 are independently selected from H, substituted or unsubstituted alkyl and substituted or unsubstituted alkanoyl; R24 and R25 are independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted aryloxy, substituted or unsubstituted oxazolidin-2-yl , (CH2) tOH, CO2H, CO2-alkyl, CONH2, CONH-alkyl, CON (alkyl) 2, OH, SH, S-alkyl, S-aryl, SO-alkyl, SO-aryl, SO2-alkyl, SO2- aryl, SO3H, SCF3, CN, halogen, CF3, NO2, (CH2) uNR22R23, SO2NH2, OCH2CH2NH2, OCH2CH2NH-alkyl and OCH2CH2N (alkyl) 2; Z = 1, 2, 3, 4, 5 or 6.
[047] Additional antimicrobial compounds are also described previously in U.S. Patent No. 8,106,031 and International Patent Application WO 2007 / 131072A2, the contents of which are incorporated herein in full by reference.
: em que A e D juntamente com os átomos de carbono aos quais eles estão ligados formam um anel fundido de 5, 6 ou 7 membros que pode ser substituído por Ci-6-alquila, Ci-6-alcóxi, hidróxi, halogênio, nitro, nitrila, amino, amino substituído por um ou mais grupos Ci-6-alquila, carbóxi, acila, arilóxi, carbonamido, carbonamido substituído por Ci-6-alquila, sulfonamido ou trifluormetila, ou o anel fundido pode ligar dois anéis oxaborol; X é um grupo -CR7R8, em que R7 e R8 são cada um, independentemente, hidrogênio, Ci-6-alquila, nitrila, nitro, arila, aralquila ou os símbolos R7 e R8 juntamente com o átomo de carbono ao qual eles estão ligados formam um anel alicíclico; e R6 é hidrogênio, Ci-is-alquila, Ci-is-alquila substituída por Ci-6-alcóxi, Ci-6-al- quiltio, hidróxi, amino, amino substituído por Ci-ie-alquila, carbóxi, arila, ariloxila, carbonamido, (carbonamido substituído por Ci-6-alquila, arila ou aralquila), aralquila, arila, heteroarila, cicloalquila, Ci-i8-alquilenoamino, Ci-w-alquilenoamino substituído porfe- nila, O-6-alcóxi ou Ci-6-alquiltio, carbonilalquilenoamino ou um radical de fórmula (V): em que A, D e X são como aqui definidos antes, exceto para boronoftalida; e seus sais agricolamente aceitáveis.[048] In some embodiments, the volatile antimicrobial compound of the invention has the structure of formula (IV) : where A and D together with the carbon atoms to which they are attached form a fused 5, 6 or 7 membered ring that can be replaced by Ci-6-alkyl, Ci-6-alkoxy, hydroxy, halogen, nitro , nitrile, amino, amino substituted by one or more Ci-6-alkyl, carboxy, acyl, aryloxy, carbonamido, carbonamido substituted by Ci-6-alkyl, sulfonamido or trifluoromethyl, or the fused ring can connect two oxaborol rings; X is a -CR7R8 group, where R7 and R8 are each, independently, hydrogen, C1-6-alkyl, nitrile, nitro, aryl, aralkyl or the symbols R7 and R8 together with the carbon atom to which they are attached form an alicyclic ring; and R6 is hydrogen, Ci-is-alkyl, Ci-is-alkyl substituted by Ci-6-alkoxy, Ci-6-alkylthio, hydroxy, amino, amino substituted by Ci-ie-alkyl, carboxy, aryl, aryloxy , carbonamido, (carbonamido substituted by C1-6-alkyl, aryl or aralkyl), aralkyl, aryl, heteroaryl, cycloalkyl, C1-8 alkyleneamino, C1-6 alkyleneamino substituted by phenyl, O-6-alkoxy or C1- 6-alkylthio, carbonylalkyleneamino or a radical of formula (V) : where A, D and X are as defined herein before, except for boronophthalide; and its agriculturally acceptable salts.
em que A, D e X são definidos como acima; Y é um grupo de ligação divalente alquileno, contendo até 18 átomos de car-bono, ou um grupo de ligação divalente alquileno, contendo até 18 átomos de carbono, que é substituído porfenila, Ci-6-alcóxi, Ci-6-alquiltio; carbonilalquilenoamino; e R3 e R4 são cada um, independentemente, hidrogênio, Ci-is-alquila ou fenila, ou R3 juntamente com Y, ou parte de Y, forma um anel de 5, 6 ou 7 membros contendo um átomo de nitrogênio.[049] In one embodiment, the volatile antimicrobial compound of the invention has the structure of formula (IX): where A, D and X are defined as above; Y is a divalent alkylene bonding group, containing up to 18 carbon atoms, or a divalent alkylene bonding group, containing up to 18 carbon atoms, which is replaced by phenyl, C1-6 alkoxy, C1-6 alkylthio; carbonylalkyleneamino; and R3 and R4 are each, independently, hydrogen, Ci-is-alkyl or phenyl, or R3 together with Y, or part of Y, forms a 5-, 6- or 7-membered ring containing a nitrogen atom.
em que A, D e X são definidos como acima; n é 1,2 ou 3; R3 é hidrogênio, Ci-is-alquila ou fenila; e R5 e R6 são cada um, independentemente, hidrogênio, alquila contendo até um total de 16 átomos de carbono ou fenila.[050] In another embodiment, the volatile antimicrobial compound of the invention has the structure of formula (X): where A, D and X are defined as above; n is 1,2 or 3; R3 is hydrogen, Ci-is-alkyl or phenyl; and R5 and R6 are each, independently, hydrogen, alkyl containing up to a total of 16 carbon atoms or phenyl.
[051] Additional antimicrobial compounds are also described previously in U.S. Patent No. 5,880,188, the contents of which are incorporated herein in full as a reference.
em que cada R é independentemente hidrogênio, alquila, alqueno, alquino, haloalquila, haloalqueno, haloalquino, alcóxi, alquenóxi, haloalcóxi, arila, heteroarila, arilalquila, arilalqueno, arilalquino, heteroarilalquila, heteroarilalqueno, heteroarilal- quino, halogênio, hidroxila, nitrila, amina, éster, ácido carboxílico, acetona, álcool, sulfeto, sulfóxido, sulfona, sulfoximina, sulfilimina, sulfonamida, sulfato, sulfonato, ni- troalquila, amida, oxima, imina, hidroxilamina, hidrazina, hidrazona, carbamato, tiocar- bamato, ureia, tioureia, carbonato, arilóxi ou heteroarilóxi; n = 1,2, 3 ou 4; B é boro; X = (CR2)m, em que m = 1,2, 3 ou 4; Y é alquila, alqueno, alquino, haloalquila, haloalqueno, haloalquino, alcóxi, al- quenóxi, haloalcóxi, arila, heteroarila, arilalquila, arilalqueno, arilalquino, heteroarilal- quila, heteroarilalqueno, heteroarilalquino, hidroxila, nitrila, amina, éster, ácido carboxílico, cetona, álcool, sulfeto, sulfóxido, sulfona, sulfoximina, sulfilimina, sulfonamida, sulfato, sulfonato, nitroalquila, amida, oxima, imina, hidroxilamina, hidrazina, hidra- zona, carbamato, tiocarbamato, ureia, tioureia, carbonato, arilóxi ou heteroarilóxi; com a condição de que R não seja arilóxi ou heteroarilóxi, quando Y é hidro-xila; e seus sais agricolamente aceitáveis.[052] In another aspect, a method of using a volatile antimicrobial compound against pathogens that affect meat, plants or parts of plants is provided. The method consists of contacting the pieces of meat, plants or parts of plants with an effective amount of the volatile antimicrobial compound of formula (VI): where each R is independently hydrogen, alkyl, alkene, alkaline, haloalkyl, haloalkene, haloalkine, alkoxy, alkoxy, haloalkoxy, aryl, heteroaryl, arylalkyl, arylalkene, arylalkyl, heteroarylalkyl, heteroarylalkyl, heteroaryl, alkaline, heteroaryl, heteroaryl amine, ester, carboxylic acid, acetone, alcohol, sulfide, sulfoxide, sulfone, sulfoximine, sulfylimine, sulfonamide, sulfate, sulfonate, nitroalkyl, amide, oxime, imine, hydroxylamine, hydrazine, hydrazone, carbamate, thiocarbamate, urea , thiourea, carbonate, aryloxy or heteroaryloxy; n = 1,2, 3 or 4; B is boron; X = (CR2) m, where m = 1,2, 3 or 4; Y is alkyl, alkene, alkaline, haloalkyl, haloalkene, haloalkine, alkoxy, alkenoxy, haloalkoxy, aryl, heteroaryl, arylalkyl, arylalkene, arylalkine, heteroarylalkyl, heteroarylalkyl, heteroaryl, heteroaryl, heteroaryl, heteroaryl , ketone, alcohol, sulfide, sulfoxide, sulfone, sulfoximine, sulfylimine, sulfonamide, sulfate, sulfonate, nitroalkyl, amide, oxime, imine, hydroxylamine, hydrazine, hydra-zone, carbamate, thiocarbamate, urea, thiourea, carbonate, aryloxy or aryloxy or aryloxy ; with the proviso that R is not aryloxy or heteroaryloxy, when Y is hydroxyl; and its agriculturally acceptable salts.
em que W = (CH2)q em que q é 1,2 ou 3.[053] In one embodiment, the volatile antimicrobial compound has a structure of formula (VII): where W = (CH2) q where q is 1,2 or 3.
[054] In another embodiment, the volatile antimicrobial compound has a structure of
[055] In an embodiment of the method provided, the pathogen is selected from the group consisting of Alternariaspp., Aspergillusspp., Botryospheria spp., Botrytis spp., Byssochlamys spp., Colletotrichum spp., Diplodia spp., Fu-sarium spp., Geotrichum spp., Lasiodiplodia spp., Monolinia spp., Mucor spp., Penicillium spp., Peziculaspp., Phomopsis spp., Phytophthora spp., Pythium spp., Rhizoptosia spp., Rhizopus spp., Sclerotinia spp. and Venturiaspp. In another embodiment, the pathogen is selected from the group consisting of Erwiniaspp., Pectobacterium spp., Pseudomonasspp., Ralstonia spp., Xanthomonasspp., Salmo-nellaspp., Escherichiaspp., Listeriaspp., Bacillusspp., Shigellaspp. and Staphylococ-cusspp. In another embodiment, the pathogen is selected from the group consisting of Candidaspp., Debaryomycesspp., Bacillusspp., Campylobac-terspp., Clostridiumspp., Cryptosporidiumspp., Giardiaspp., Vibriospp. and Yersinia spp. In another embodiment, the method comprises pre-harvest treatment or post-harvest treatment. In an additional embodiment, the pre-harvest treatment is selected from the group consisting of seed treatment and transplant treatment. In another embodiment, the post-harvest treatment is selected from the group consisting of treatment during packaging in the field, treatment during palletization, treatment in the box, treatment during transport and treatment during storage and / or throughout the distribution network.
[056] In another embodiment, the plants or parts of plants comprise transgenic plants or parts of transgenic plants. In another embodiment, the plants or parts of plants are selected from the group consisting of corn, wheat, cotton, rice, soy and canola. In another embodiment, the plants or parts of plants are selected from the group consisting of bananas, pineapples, citruses that include oranges, lemon, lime, grapefruit and other citruses, grapes, watermelon, cantaloupe, melon and other melons , apple, peach, pear, cherry, kiwi, mango, nectarine, guava, papaya, persimmon, pomegranate, avocado, fig and berries including strawberry, blueberry, raspberry, blackberry, blackberry, currants and other types of berries. In another embodiment, the vegetable is selected from the group consisting of tomatoes, potatoes, sweet potatoes, manioc, pepper, peppers, carrots, celery, pumpkin, eggplant, cabbage, cauliflower, broccoli, asparagus, mushrooms, onions, garlic, leeks and green beans. In an additional embodiment, the flower or part of the flower is selected from the group consisting of roses, carnations, orchids, geraniums, lilies or other ornamental flowers. In another embodiment, the meat is selected from the group of beef, bison, chicken, venison, goat, turkey, pork, sheep, fish, crustaceans, mollusks or dry-cured meat products.
[057] In one embodiment, the contact comprises the application of the volatile antimicrobial compound through modes selected from the group consisting of spray, mist, thermal or non-thermal nebulization, spraying, gas treatment and their combinations. In an additional embodiment, gas treatment is selected from the group consisting of release from a sachet, release from a synthetic or natural film, release from coating or other packaging materials, release from powder, release from a gas release generator, release using a cylinder of compressed or uncompressed gas, release from a droplet inside a box and its combinations. In another embodiment, the method further comprises the contact of meat, plants, parts of plants with a volatile plant growth regulator. In another embodiment, the volatile plant growth regulator is a cyclopropene compound. In another embodiment, the cyclopropene compound comprises 1-methylcyclopropene (1-MCP).
em que Ra é CN, C(O)NR9R10 ou C(O)OR11, em que R11 é hidrogênio, alquila substituída ou um grupo alquila não substituída, Xé N, CH e CRb; Rb é halogênio, alquila substituída ou não substituída, C(O)R12, C(O)OR12, OR12, NR12R13, em que R9, R10, R12e R13são, independentemente, hidrogênio, alquila substituída ou não substituída, heteroalquila substituída ou não substituída, cicloal- quila substituída ou não substituída, heterocicloalquila substituída ou não substituída, arila substituída ou não substituída, ou heteroarila substituída ou não substituída; com a condição de que R9 e R10, juntamente com os átomos aos quais eles estão ligados, ssejam opcionalmente combinados para formar um anel heterocicloal-quila de 4 a 8 membros substituído ou não substituído; e com a condição de que R12 e R13, juntamente com os átomos aos quais eles estão ligados, sejam opcionalmente combinados para formar uma anel heterocicloalquila de 4 a 8 membros substituído ou não substituído; e seus sais agricolamente aceitáveis .[058] In another aspect, a method of using a volatile antimicrobial compound against pathogens that affect meat, plants or parts of plants is provided. The method consists of contacting the pieces of meat, plants or parts of plants with an effective amount of the volatile antimicrobial compound of formula (VIII): where Ra is CN, C (O) NR9R10 or C (O) OR11, where R11 is hydrogen, substituted alkyl or an unsubstituted alkyl group, X is N, CH and CRb; Rb is halogen, substituted or unsubstituted alkyl, C (O) R12, C (O) OR12, OR12, NR12R13, where R9, R10, R12 and R13 are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl , substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; with the proviso that R9 and R10, together with the atoms to which they are attached, are optionally combined to form a substituted or unsubstituted 4- to 8-membered heterocycloalkyl ring; and with the proviso that R12 and R13, together with the atoms to which they are attached, are optionally combined to form a substituted or unsubstituted 4- to 8-membered heterocycloalkyl ring; and its agriculturally acceptable salts.
[059] In one embodiment, the volatile antimicrobial compound of the invention has the structure of formula (X):
[060] In another embodiment, the volatile antimicrobial compound of the invention is selected from:
[061] In another embodiment, the volatile antimicrobial compound of the invention is selected from:
[062] In another embodiment, the volatile antimicrobial compound of the invention is selected from:
:[063] In one embodiment, the volatile antimicrobial compound of the invention has the structure of formula (XI) :
[064] In another embodiment, the volatile antimicrobial compound of the invention is selected from:
[065] In another embodiment, the volatile antimicrobial compound of the invention is selected from:
[066] In another embodiment, the volatile antimicrobial compound of the invention is selected from:
:[067] In one embodiment, the volatile antimicrobial compound of the invention has the structure of formula (XII) :
[068] In another embodiment, the volatile antimicrobial compound of the invention is selected from:
[069] In one embodiment, the volatile antimicrobial compound of the invention is selected from:
[070] In another embodiment, the volatile antimicrobial compound of the invention is selected from:
[071] In one embodiment, Rb is selected from fluorine and chlorine. In another embodiment, Rb is selected from OR26 and NR27R28. In another embodiment, when Rb is OR26, R26 is selected from H, substituted or unsubstituted alkyl, heteroalkyl or unsubstituted, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted and substituted heteroaryl or not replaced. In another embodiment, when Rb is OR26, R26 is selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl and substituted or unsubstituted cycloalkyl. In another embodiment, when Rb is OR26, R26 is unsubstituted C1-6 alkyl. In another embodiment, when Rb is OR26, R26 is unsubstituted cycloalkyl. In another embodiment, when Rb is OR26, R26 is an alkyl group, substituted by a member selected from substituted or unsubstituted C1-6 alkoxy. In another embodiment, when Rb is OR26, R26 is an alkyl group, substituted by at least one halogen. In another embodiment, when Rb is OR26, R26 is an alkyl group, substituted by at least an oxo moiety.
[072] In another embodiment, when Rb is OR26, R26 is a member selected from CH3, -CH2CH3, - (CH2) 2CH3, -CH (CH3) 2, -CH2CF3, -CH2CHF2, - CH2CH2 (OH ), -CH2CH2 (OCH3), -CH2CH2 (OC (CH3) 2), -C (O) CH3, -CH2CH2OC (O) CH3, -CH2C (O) OCH2CH3, -CH2C (O) OC (CH3) 3, - (CH2) 3C (O) CH3, -CH2C (O) OC (CH3) 3, cyclopentyl, cyclohexyl,
[073] In another embodiment, when Rb is NR27R28, R27 and R28 are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted aryl or unsubstituted, and substituted or unsubstituted heteroaryl. In another embodiment, when Rb is NR27R28, R27 is H or unsubstituted alkyl and R28 represents an unsubstituted alkyl group or alkyl substituted by a member selected from hydroxyl, phenyl, unsubstituted alkoxy and alkoxy substituted by a phenyl group. In an additional embodiment, when Rb is NR27R28, R27 is H or CH3.
[074] In another embodiment, when Rb is NR27R28, R27 and R28 are independently selected from substituted or unsubstituted alkyl. In another embodiment, when Rb is NR27R28, R27 represents an unsubstituted alkyl group and R28 is substituted or unsubstituted alkyl. In another embodiment, when Rb is NR27R28, R27 represents an unsubstituted alkyl group and R28 represents an alkyl group substituted by a selected member of substituted or unsubstituted alkoxy and hydroxyl. In another embodiment, when Rb is NR27R28, R27 represents an unsubstituted alkyl group and R28 represents an alkyl group substituted by unsubstituted alkoxy. In another embodiment, when Rb is NR27R28, R27 represents an unsubstituted alkyl group and R28 represents an alkyl group, substituted by phenyl-substituted alkoxy. In another embodiment, when Rb is NR27R28, R27 represents an unsubstituted alkyl group and R28 represents an alkyl group, substituted by unsubstituted alkoxy. In another embodiment, when Rb is NR27R28, R27 and R28, together with the nitrogen to which they are attached, are combined to form a substituted or unsubstituted 4- to 8-membered heterocycloalkyl ring. In another embodiment, when Rb is NR27R28, R27 and R28, together with the nitrogen to which they are attached, are combined to form a substituted or unsubstituted 5- or 6-membered heterocycloalkyl ring.
[075] In another embodiment, Rb is selected from N (CHs) 2, N (CH3) (CH2CH2 (OCH3)), N (CH3) (CH2CH2OH), NH2, NHCH3, NH (CH2CH2 (OCH3)), NH (CH2CH2 (OCH2Ph), NH (CH2Ph), NH (C (CH3) 3) and NH (CH2CH2OH). In another embodiment, Rb is selected from
[076] Additional antimicrobial compounds are also described previously in U.S. Patent No. 8,039,450, and in US patent application publication 2009/0291917, the contents of which are incorporated herein in full as a reference.
em que cada um de R1, R2, R3 e R4 é independentemente selecionado do grupo que consiste de H e um grupo químico com a fórmula:-(L)n-Z em que n é um número inteiro de 0 a 12. Cada L é um radical bivalente. Gru-pos L adequados incluem, por exemplo, grupos contendo um ou mais átomos seleci-onados de H, B, C, N, O, P, S, Si, ou misturas dos mesmos. Os átomos em um grupo L podem estar ligados uns aos outros por ligações simples, ligações duplas, ligações triplas ou suas misturas. Cada grupo L pode ser linear, ramificado, cíclico ou uma combinação dos mesmos. Em qualquer um grupo R (isto é, qualquer um de R1, R2, R3 e R4), o número total de heteroátomos (isto é, átomos que não são nem H nem C) é de 0 a 6. De modo independente, em qualquer um grupo de R, o número total de átomos diferentes de hidrogênio é de 50 ou menos. Cada Z é um radical monovalente. Cada Z é independentemente selecionado do grupo que consiste de hidrogênio, halo, ciano, nitro, nitroso, azido, clorato, bromato, iodato, isocianato, isocyanido, isotiocia- nato, pentafluortio e um grupo químico G, em que G é um sistema de anel de 3 a 14 membros.[077] The practice of the present invention involves the use of one or more cyclopropene compounds. As used herein, a cyclopropene compound is any compound with the formula where each of R1, R2, R3 and R4 is independently selected from the group consisting of H and a chemical group with the formula :-( L) nZ where n is an integer from 0 to 12. Each L is a bivalent radical. Suitable L groups include, for example, groups containing one or more atoms selected from H, B, C, N, O, P, S, Si, or mixtures thereof. The atoms in a group L can be linked to each other by single bonds, double bonds, triple bonds or mixtures thereof. Each group L can be linear, branched, cyclic or a combination of them. In any one group R (that is, any one of R1, R2, R3 and R4), the total number of heteroatoms (that is, atoms that are neither H nor C) is 0 to 6. Independently, in any one group of R, the total number of atoms other than hydrogen is 50 or less. Each Z is a monovalent radical. Each Z is independently selected from the group consisting of hydrogen, halo, cyano, nitro, nitrous, azido, chlorate, bromate, iodate, isocyanate, isocyanide, isothiocyanate, pentafluortium and a chemical group G, where G is a system of 3 to 14 member ring.
[078] Groups R1, R2, R3 and R4 are independently selected from the appropriate groups. Among the groups that are suitable for use as one or more of R1, R2, R3 and R4 are, for example, aliphatic groups, oxyaliphatic groups, alkylphosphonate groups, cycloaliphatic groups, cycloalkylsulfonyl groups, cycloalkylamino groups, heterocyclic groups, aryl groups , heteroaryl groups, halogens, silyl groups, other groups and mixtures and combinations thereof. Groups that are suitable for use as one or more of R1, R2, R3 and R4 can be substituted or unsubstituted.
[079] Suitable groups R1, R2, R3 and R4 include, for example, aliphatic groups. Some suitable aliphatic groups include, for example, alkyl, alkenyl and alkynyl groups. Suitable aliphatic groups include linear, branched, cyclic groups or a combination thereof. Independently, suitable aliphatic groups can be substituted or not substituted.
[080] As used herein, a chemical group of interest is said to be "substituted" if one or more hydrogen atoms in the chemical group of interest are substituted by a substituent.
[081] Also among the groups R1, R2, R3 and R4 are, for example, substituted and unsubstituted heterocyclyl groups that are linked to the cyclopropene compound by means of an intervening oxy group, amino group, carbonyl group or sulfonyl group ; examples of such groups R1, R2, R3 and R4 are heterocyclyloxy, heterocyclylcarbonyl, dieterocyclylamino and dieterocyclylaminosulfonyl.
[082] Also among the suitable groups R1, R2, R3 and R4 are, for example, substituted and unsubstituted heterocyclic groups that are linked to the cyclopropene compound by means of an intervening oxy group, amino group, carbonyl group, sulfonyl group, thioalkyl group or aminosulfonyl group; examples of such groups R1, R2, R3 and R4 are diethyl arylamino, heteroarylthioalkyl and dieteroaryl aminosulfonyl groups.
[083] Also suitable groups R1, R2, R3 and R4 are, for example, hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, nitrous, azide, chlorate, bromate, iodate, isocyanate, isocyanide, isothiocyanate, pentafluortium; acetoxy, carboetoxy, cyanate, nitrate, nitrite, perchlorate, alenyl, butylmercapto, diethylphosphonate, dimethylphenylsilyl, iso-quinolyl, mercapto, naphthyl, phenoxy, phenyl, piperidine, pyridyl, quinolyl, triethylsilyl, trimeyl; and substituted analogues thereof.
[084] As used herein, the chemical group G is a 3- to 14-membered ring system. Ring systems suitable as chemical group G may be substituted or unsubstituted, which may be aromatic (including, for example, phenyl and naphthyl) or aliphatic (including unsaturated, aliphatic, partially saturated or aliphatic aliphatic); and can be carbocyclic or heterocyclic. Among heterocyclic G groups, some suitable heteroatoms are, for example, nitrogen, sulfur, oxygen and their combinations. Ring systems suitable as chemical group G can be monocyclic, bicyclic, tricyclic, polycyclic, spiral or fused; between suitable ring systems such as chemical group G which are bicyclic, tricyclic or fused, the various rings in a single chemical group G can all be of the same type or can be of two or more types (for example, an aromatic ring can be fused with an aliphatic ring).
[085] In one embodiment, one or more of R1, R2, R3 and R4 are hydrogen or (C1-C10) alkyl. In another embodiment, each of R1, R2, R3 and R4 is hydrogen or (C-i-Cs) alkyl. In another embodiment, each of R1, R2, R3 and R4 is hydrogen or (C1-C4) alkyl. In another embodiment, each of R1, R2, R3 and R4 is hydrogen or methyl. In another embodiment, R1 is (C1-C4) alkyl and each of R2, R3 and R4 is hydrogen. In another embodiment, R1 represents methyl and each of R2, R3 and R4 is hydrogen, and the cyclopropene compound is known herein as 1-methylcyclopropene or "1-MCP".
em que R é um grupo alquila, alquenila, alquinila, cicloalquila, cicloalquilal- quila, fenila ou naftila substituído ou não substituído, em que os substituintes são, independentemente, halogênio, alcóxi ou fenóxi substituído ou não substituído. Em uma modalidade de realização, R é C1-8 alquila. Noutra modalidade de realização, R é metila.[086] In another embodiment, cyclopropene has the formula: wherein R is a substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, phenyl or naphthyl group, where the substituents are independently substituted or unsubstituted halogen, alkoxy or phenoxy. In one embodiment, R is C1-8 alkyl. In another embodiment, R is methyl.
em que R1 é um grupo alquila C1-C4 substituído ou não subustiuído, alquenila C1-C4, alquinila C1-C4, cicloalquila C1-C4, cicloalquilalquila, fenila ou naftila; e R2, R3 e R4 são hidrogênio. Noutra modalidade de realização, o ciclopropeno compreende 1- metilciclopropeno (1-MCP).[087] In another embodiment, cyclopropene is a formula wherein R1 is a substituted or unsubstituted C1-C4 alkyl group, C1-C4 alkenyl, C1-C4 alkynyl, C1-C4 cycloalkyl, cycloalkylalkyl, phenyl or naphthyl; and R2, R3 and R4 are hydrogen. In another embodiment, the cyclopropene comprises 1-methylcyclopropene (1-MCP).
[088] As used herein, the term "transgene vector" refers to a vector that contains an inserted DNA segment, the "transgene" that is transcribed into mRNA or replicated as RNA in a host cell. The term "transgene" refers not only to the portion of inserted DNA that is converted to RNA, but also to the portions of the vector that are necessary for RNA transcription or replication. A transgene typically comprises a gene of interest, but it need not necessarily comprise a polynucleotide sequence that contains an open reading frame capable of producing a protein.
[089] Meat, plants or parts of plants can be treated in the practice of the present invention. An example is the treatment of whole plants; another example is the treatment of whole plants, while they are planted in the soil, before harvesting parts of useful plants.
[090] All plants that provide parts of useful plants can be treated in the practice of the present invention. Examples include plants that provide fruits, vegetables and grains.
[091] As used herein, the term "plant" includes dicot plants and monocot plants. Examples of dicotyledonous plants include tobacco, Arabidopsis, soy, tomato, papaya, canola, sunflower, cotton, alfalfa, potato, vine, pigeon pea, Brassica, chickpeas, sugar beet, rapeseed, watermelon, melon, pepper, peanuts, squash, radish, spinach, squash, broccoli, cabbage, carrots, cauliflower, celery, Chinese cabbage, cucumber, eggplant and lettuce. Examples of monocotyledonous plants include maize, rice, wheat, sugar cane, barley, rye, sorghum, orchids, bamboo, banana, cattail, lilies, oats, onions, millet and triticale. Examples of fruit include bananas, pineapples, oranges, grapes, grapefruit, watermelons, melons, apples, peaches, pears, kiwis, mangoes, nectarines, guava, persimmons, avocados, lemons, figs and berries.
[092] Those skilled in the art will understand that certain variation may exist based on the description provided. Thus, the following examples are presented for the purpose of illustrating the invention and should not be construed as limiting the scope of the invention or claims. EXAMPLES Example 1
[093] 12-well microtiter plates (7 ml volume per well) are used for the in vitro inhibition test of volatile antimicrobial compounds. A 3 ml volume of Potato Dextrose Agar (ADB) is added to each well. After cooling, 1 pL of 1 x 106 per ml of Botrytis cinerea spore suspension is pipetted in the center of the agar. For the first experiment, inoculated plates are allowed to germinate for 5 days at 4 ° C. For the second experiment, plaques are inoculated immediately before treatment with volatile fungicide. Small Whatman No. 1 filter discs (Cat. No. 1001-0155) are placed, in duplicate, under the underside of a sealing film from the PCR polyethylene plate. To determine the minimum inhibitory concentration (MIC), Compound A (benzoxaborol, Figure 1) is diluted in acetone and the appropriate amount of compound is added to discs in a dose-dependent manner (1.25 to 0.0006 mg / disc). The acetone is allowed to evaporate for 5 minutes. The upper space around the inoculum of Botrytis cinerea is then sealed inside the well by the film with the adherent disk containing the fungicide. The plates are inverted, placed on the treated discs and sealed to prevent any of the chemicals from discharging from the disc and falling on the inoculated agar. After 14 days of storage at 4 ° C, cultures are evaluated for percentage growth in relation to control. Regardless of whether the spores germinated for 5 days, or whether the treatment started right after inoculation of the plates (~ 15 minutes), 100% control of the fungal pathogen dropped to 0.005 mg. The experimental results are summarized in Table 1. The results suggest that Compound A is capable of killing Botrytis cinerea spores and inhibiting mycelial growth with the same concentration. Thus, Compound A (Figure 1) shows 100% efficacy in inhibiting in vitro fungal growth, at a rate of 0.005 mg / disc. Example 2
[094] A total of 14 antimicrobial compounds are tested using the in vitro inhibition assay in Example 1. All 14 compounds are applied to Whatman discs, in duplicate, in a dose-dependent manner (0.31 to 0.0006 mg /disco). The results show that X11820679 (Compound A) provides the best control of Botrytis cinerea, with 100% cover up to 0.005 mg / disc. Other compounds, such as X11820681, X11820683 and X11820684 conferred 100% control up to 0.023; 0.04 and 0.08 mg / disc, respectively. The tested compounds and their respective MICs are shown in Figure 3. The results of nine compounds are summarized in Table 2, in which the other five compounds show no activity detected at the tested intervals Example 3
[095] Compound B (Figure 2; 2- (hydroxymethyl) phenylboronic acid cyclic monoester, a ctes-fluorine analog of X11820679) is evaluated in a similar manner to that described in Examples 1 and 2 above. The compounds are applied to Whatman filter paper at rates of 0.5 mg to 0.0039 mg / disc. Results show that Compound B inhibits 100% of Botrytis cinerea at a rate of 0.0078 mg / disc. Example 4
[096] In order to evaluate the in vivo activity of volatile antimicrobial compounds, a volatile bioassay is developed using green table grapes. The fruits are placed individually in a 20 pL scintillation bottle, with the stem wound facing upwards. The new stem wound is inoculated with 10 µL of 1 x 106 per ml of Botrytis cinerea spore suspension. Whatman filter paper (Cat. No. 1822-024) is placed inside duplicate vial caps. For MIC determination, Compound A (Figure 1) is diluted in acetone and the appropriate amount of compound is added to discs in a dose dependent manner (2.5 to 0.0024 mg / disc). The acetone is allowed to evaporate for 5 minutes. The vials are then covered with lids containing the fungicide and left for 14 days at 4 ° C. After storage, the fruits are evaluated for disease incidence and phytotoxicity. The results are summarized in Table 3 and there is 100% control of Botrytis cinerea up to 0.04 mg / disc and no evidence of phytotoxicity at any of the rates assessed. Representative photographs of exemplary in vivo inhibition results using Compound A are shown in Figure 4, where 0.04 mg of Compound A shows 100% inhibition and 0.0024 mg of Compound A shows no inhibition. Example 5
[097] In order to assess the in vivo activity of volatile antimicrobial compounds, a volatile bioassay is developed using strawberries. Two fruits are placed in a 240 ml jar, with the cup facing downwards. A new wound is inoculated with 20 µl of 1 x w6 per ml of Botrytis cinerea spore suspension. Whatman filter paper (Cat. No. 1822-024) is placed inside duplicate jar lids. For MIC determination, Compound A (benzoxaborol; Figure 1) is diluted in acetone and the appropriate amount of compound is added to discs in a dose-dependent manner (2.5 to 0.005 mg / disc). For MIC determination, Compound B (benzoxaborol; Figure 2) is diluted in acetone and the appropriate amount of compound is added to discs in a dose-dependent manner (2.5 to 0.005 mg / disc). The acetone is allowed to evaporate for 5 minutes. The jars are then covered with lids containing the fungicide and left for 5 days at 21 ° C. After storage, the fruits are evaluated for incidence and severity of the disease and appearance of phytotoxicity. The results are summarized in Ta-bela 4. There is 100% control of Botrytis cinerea up to 0.16 mg / disc, both for Compound A, and 100% control of Botrytis cinerea up to 0.32 mg / disc, for Compound B, and no evidence of phytotoxicity at any of the rates assessed. Example 6
Gravidade: 0 = ausência de crescimento fúngico 1 = leve infecção (<5 mm de diâmetro) 2 = infecção moderada (<1 cm de diâmetro) 3 = infecção elevada (> 1 cm de diâmetro) 4 = infecção extrema (> metade do comprimento do fruto)[098] In order to assess the in vivo dose by the activity of volatile anti-microbial compounds as a function of time, a volatile bioassay is developed using strawberry. Two fruits are placed in a 240 ml jar, with the cup facing downwards. A new wound is inoculated with 20 µl of 1 x 106 per ml of Botrytis cinerea spore suspension. Whatman filter paper (Cat. No. 1822-024) is placed inside duplicated jar lids. Compound A (benzoxaborol; Figure 1) is diluted in acetone and the appropriate amount of compound is added to discs with two rates of 0.008 or 0.125 mg. The acetone is allowed to evaporate for 5 minutes. The jars are closed with the lids containing the fungicide and incubated with the volatile fungicide for 1, 3, 6, 24 or 72 hours. After incubation, caps containing the disk with Compound A are replaced with new caps, without Compound A. All samples are kept at 21 ° C for three days, then the caps are removed and maintained for an additional 48 hours, all at 90 % RH. The are evaluated for the incidence and severity of the disease and appearance of phytotoxicity. The results are summarized in Table 5. There is 100% control of Botrytis cinerea under 0.125 mg / disc for Compound A after 6 hour exposure, and no evidence of phytotoxicity. 0.125 mg of Compound A shows 100% inhibition in vivo compared to the acetone control only. A representative result is also shown in Figure 5. Severity: 0 = no fungal growth 1 = mild infection (<5 mm in diameter) 2 = moderate infection (<1 cm in diameter) 3 = high infection (> 1 cm in diameter) 4 = extreme infection (> half the length fruit) Example 7
Classificação da Colônia: 0 = Não há colônias 1 = Microcolônias não ligadas 2 = Pequenas colônias com alguma fusão 3 = Grandes colônias se fundem[099] 12-well microtiter plates (7 mL volume per well) are used for the in vitro inhibition assay for volatile antimicrobial compounds. A volume of 3 ml of LB Agar at full concentration is added to each well. After cooling, 15 pL of Escherichia coli, adjusted to an optical density of 0.02 to 0.035 and further diluted 1/10, are pipetted into the center of the agar and titrated to distribute evenly. Small Whatman No. 1 filter discs (Cat. No. 1001-0155) are placed in duplicate under the underside of a PCR polyethylene plate sealing film. To determine the minimum inhibitory concentration (MIC), Compound A (benzoxaborol; Figure 1) is diluted in acetone and 5 mg of compound is added to disks. The acetone is allowed to evaporate for 5 minutes. The air space around the Escherichia coli inoculum is then sealed inside the well by the film with the adherent disk containing the fungicide. The plates are inverted, placed on the treated discs and sealed to prevent any of the chemicals from discharging from the disc and falling on the inoculated agar. After three days of storage at 4 ° C, cultures were transferred at 23 ° C for an additional 2 days and then evaluated for colony growth relative to the control. Experimental results are summarized in Table 6. The results suggest that Compound A is capable of inhibiting Escherichia coli. Colony Classification: 0 = No colonies 1 = Unlinked microcolonies 2 = Small colonies with some fusion 3 = Large colonies merge Example 8
Tabela 8. CIM (mg/L) de numerosos compostos de benzoxaborol aplicados como tratamento volátil contra agentes patogênicos fúngicos de plantas Bo- trytis cinerea e Penicillium expansum. Tabela 8 – Continuação Tabela 8 – Continuação Tabela 8 – Continuação[100] 12-well microtiter plates (volume 6.5 ml per well) are used for the in vitro inhibition assay for volatile antimicrobial compounds. A volume of 3 ml of Potato Dextrose Agar (ADB) in total concentration is added to each well. After cooling, 1 pL of 1 x 105 per ml of spore suspension of Botrytis cinerea, expanded Penicillium, Alternaria alternata, Monilinia fructicolaou Glomerella cingulata is piped at a point in the center of the agar. The plates are inoculated immediately before treatment with volatile fungicide. A Whatman No. 1 filter disc (Cat. No. 1001-0155) is placed, in duplicate, under the underside of a PCR polyethylene plate sealing film. To determine the minimum inhibitory concentration (MIC), compounds are diluted in acetone and the appropriate amount of compounds is added to discs in a dose-dependent manner to achieve a final aerial concentration of 1,142.9 to 0.6 mg / L. The acetone is allowed to evaporate for 5 minutes. The air space around the inoculum is then sealed inside the well by the film with the adherent disk containing the fungicide, inverting the plates on the treated disks and sealing to prevent any portion of the chemical from discharging from the disk and falling on the inoculated agar . After three days of storage at 23 ° C, cultures are evaluated for percentage growth in relation to control, based on the measurement of the diameter of fungal colonies. The experimental results are summarized in Table 1. The results indicate that benzoxaborol compounds have excellent in vitro activity against five selected plant fungal pathogens. Table 7. MIC (mg / L, aerial concentration) of numerous benzoxaborol compounds applied as a volatile treatment against numerous plant fungal pathogens (Compound 10 is the same as Compound A, and Compound 11 is the same as Compound B). Table 8. CIM (mg / L) of numerous benzoxaborol compounds applied as a volatile treatment against fungal pathogens from plants Trybenttis cinerea and Penicillium expansum. Table 8 - Continuation Table 8 - Continuation Table 8 - Continuation Example 9
[101] 12-well microtiter plates (volume 6.5 ml per well) are used for the in vitro inhibition assay for volatile antimicrobial compounds. A 3 ml volume of Potato Dextrose Agar (ADB) with total concentration is added to each well. After cooling, 1 pL of 1 x 105 per ml of spore suspension of Botrytis cinerea and Penicillium expansum is pipetted at a point in the center of the agar. The plates are inoculated immediately before treatment with volatile fungicide. A Whatman No. 1 filter disc (Cat. No. 1001-0155) is placed, in duplicate, under the underside of a PCR polyethylene plate sealing film. To determine the minimum inhibitory concentration (MIC), compounds are diluted in acetone and the appropriate amount of compounds is added to disks in a dose-dependent manner to achieve a final aerial concentration of 35.7 to 0.03 mg / L. The acetone is allowed to evaporate for 5 minutes. The air space around the inoculum is then sealed inside the well by the film with the adherent disk containing the fungicide, inverting the plates on the treated disks and sealing to prevent any portion of the chemical from discharging from the disk and falling on the inoculated agar . After three days of storage at 23 ° C, cultures are evaluated for percentage growth in relation to control, based on the measurement of the diameter of fungal colonies. The experimental results are summarized in Table 8. The results indicate that benzoxaborol compounds have excellent in vitro activity against two selected plant fungal pathogens. Example 10
Tabela 9. CIM (mg/L) de Compostos A e B aplicados como voláteis contra numerosos patógenos fúngicos de plantas [102] 12-well microtiter plates (volume 6.5 ml per well) are used for the in vitro inhibition assay for volatile antimicrobial compounds A and B (Figure 1) against numerous plant fungal pathogens. A volume of 3 ml of Potato Dextrose Agar (ADB) with total concentration is added to each well. After cooling, 1 pL of 1 x 105 per ml of spore suspension of Botrytis cinerea, Penicillium expansum, Alternaria alternata, Glomerella cingulata, Penicillium digitatum, Monilinia fruticola, Aspergillus brasiliensls, Colletotrichum acutatum, Fusarium sambuci- num, Phytophphph, phytoph Geotrichum candidum, Aspergillus niger, Diplodia gossypina or Diaporthe citri is pipetted at a point in the center of the agar. A Whatman No. 1 filter disc (Cat. No. 1001-0155) is placed, in duplicate, under the underside of a PCR polyethylene plate sealing film. To determine the minimum inhibitory concentration (MIC), test compounds are diluted in acetone and the appropriate amount of compounds is added to discs in a dose-dependent manner to achieve a final aerial concentration of 35.7 to 0.03 mg / L. The acetone is allowed to evaporate for 5 minutes. The air space around the inoculum is then sealed into the well by the film with the adherent disk containing the fungicide, inverting the plates on the treated disks and sealing to prevent any portion of the chemical from discharging from the disk and falling onto the inoculated agar . After three days of storage at 23 ° C, cultures are evaluated for percentage growth compared to control. The results shown in Ta-bela 9 demonstrate the ability of benzoxaborol A and B compounds to control the growth of numerous fungal pathogens by means of volatile activity. Table 9. MIC (mg / L) of Compounds A and B applied as volatiles against numerous plant fungal pathogens Table 9. MIC (mg / L) of Compounds A and B applied as volatiles against numerous plant fungal pathogens Example 11
[103] 12-well microtiter plates (volume 6.5 ml per well) are used for the in vitro inhibition assay for volatile antimicrobial compounds A (Figure 1) against numerous bacterial pathogens. A 3 ml volume of Nutrient Agar is added to each well and allowed to dry before introducing the pathogens. Cell suspensions of Escherichia coli, Pectobacterium carotovorum, Xanthomonas axonopodise Salmonella enteral are adjusted to an optical density of 0.2 to 0.35 and additionally diluted 1/10; 15 pL are pipetted in the center of each well and titrated to distribute evenly. A Whatman No. 1 filter paper (CAT. 1001- 0155) is placed under the underside of a PCR polyethylene plate sealing film. To determine the minimum bacterial concentration (CBM), Compound A is diluted in acetone and 50 pL are applied to discs, in duplicate, in a dose dependent manner in order to reach a final aerial concentration of 71.4 to 0.03 mg / L. The acetone is allowed to evaporate for 5 minutes. The films with the treated discs are then applied over inoculated and sealed plates. The plates are inverted and incubated at 23 ° C for 48 hours. After the incubation period, the bacterial colonies are dislodged in sterile water containing Tween 80 (0.001%) and the OD (600 nm) is determined. The results are summarized in Table 10, in which the air concentration necessary to control at least 80% of bacterial growth is recorded. Compound A shows good antimicrobial activity against numerous bacteria in this in vitro assay. Table 10. Rate (mg / L) of Compound A that offers at least 80% control against bacterial pathogens Example 12
[104] In order to evaluate the in vivo activity of volatile antimicrobial compound 10, a volatile bioassay is developed to assess the control of fresh beef Es-cherichia coli and Salmonella entericade. The meat is washed to remove any natural inoculum, rinsing in warm water for 2 min. Two strips, single layer, are placed in a sterile Snapwarede 2.6 L airtight container (Model No. 109842). Table 11. Colony forming unit (CFU / mL) and reductions in meat log E. coli and S. enterica after a volatile treatment with Compound A.
[105] Each strip is inoculated on the surface by placing 20 µl of suspensions of E. coli or S. enterica cells that are adjusted to an optical density of 0.35 (600 nm) and additionally diluted 1/10. To determine the effectiveness, powdered Compound A is introduced into the container with a sublimation device (copper tube heated to 200 ° C with fan flow at 0.5 L / min) at a speed necessary to reach a final air concentration of 100 mg / L. The containers are then incubated for two days at 21 ° C. After treatment, the meat is washed, with collected wash, diluted in series, plated on nutrient agar and then incubated for an additional 24 hours at 37 ° C. Bacterial colonies are counted and expressed as colony forming units (CFU / ml), with the log reduction calculated in relation to the control. The results presented in Table 11 show good antimicrobial activity of compound A against E. coli and S. enterica in this in vivo assay using beef. Compound A demonstrates a 3.17 log reduction (> 99.9%) of E. coli and a log reduction of 2 for S. enterica. Example 13
[106] In order to assess in vivo activity of volatile antimicrobial Compound A in the control of Botrytis cinerea in ornamental flowers, a volatile bioassay is developed using white carnations. Five carnations are placed in an 800 ml jar containing 200 ml of a common commercial flower preservative. Five jars are then placed in a 117 L Rubbermaid storage box (Cat. No. 2244). The petals are inoculated uniformly by spraying with 5 ml of 1x105 spore suspension / ml of Botrytis cinerea. The vat is hermetically closed. For the treatment application, Compound A is dissolved in an aqueous solution of 1,2-propylene glycol (3: 1) and 5 ml of solution are volatilized inside the container using an ES-100-H SmartFog system (Reno , NV), through a 1.27 cm side door that is sealed immediately after application. The flowers are incubated for 3 days at 21 ° C. After storage, flowers are assessed for incidence, based on the presence of disease in flower petals compared to untreated control flowers for up to 8 days at 21 ° C, with results summarized in Table 12. Compound A at 1 mg / L shows 0% incidence two days after treatment removal and only 16% incidence after 8 days, and generally demonstrates good volatile antimicrobial activity against Botrytis cinerea in this in vivo analysis of infection in an ornamental flower. Table 12. Incidence of Botrytis cinerea in carnations treated with Compound A Example 14
[107] A test similar to that described above is also carried out on white carnations (treated with or without the commercial antithylene silver thiosulfate compound, STS) with natural inoculum. Compound A is dissolved in an aqueous solution of 1,2-propylene glycol (3: 1) and 5 mL of the volatilized solution using an ES-100-H SmartFog system (Reno, NV), through a side door of 1, 27 cm which is sealed immediately after application, or dissolved in acetone and applied to a 42.5 mm Whatman No. 1 filter disc (Cat. No. 1001-042), and placed in a watch glass after allowing the acetone evaporates for 5 minutes. The flowers are incubated for 3 days at 21 ° C. After storage, the flowers are evaluated for an additional eight days for disease severity, based on the number of lesions present in the petals and sepals of the flowers. The results shown in Table 13 show good antimicrobial activity against Botrytis in this in vivo analysis. Table 13. Severity of Botrytis cinerea after eight days of life, based on the number of lesions on the petals and sepals after treatment with active or passive volatile mist with Compound 10. Example 15
* Classificação de Gravidade 0 = Sem doença 1 = Escurecimento e pequenas lesões nas sépalas e pétalas 2 = Escurecimento, pétalas cobertas com esporos de fungos 3 = Escurecimento, pétalas cobertas com esporos de fungos, alguma queda de pétalas 4 = Escurecimento, pétalas cobertas com esporos de fungos, algumas flores abortadas[108] A test similar to that described above is also performed on white roses with a natural inoculum. Five white roses are placed in an 800 mL jar containing 200 mL of a common commercial flower preservative. Three jugs are then placed in a 117 L Rubbermaid storage box (Cat. No. 2244). Two small fans are placed at the opposite ends of the container to aid the volatile distribution of Compound 10. The vat is closed tightly, then Compound A is diluted in acetone and then pipetted onto a 3.81 cm cotton strip. x 2.54 cm. The acetone is allowed to evaporate for five minutes. Compound A is therefore introduced into the containers by a sublimation device (copper tube heated to 200 ° C with fan flow at 0.5 L / min), to obtain a final aerial concentration of 0.04; 0.2 and 1 mg / L, through a 1.27 cm side door that is sealed immediately after application. Alternatively, Compound A is pipetted onto a 42.5 mm Whatman No. 1 filter disc (Cat. No. 1001-042), supported by a watch glass, in which the acetone is allowed to evaporate for 5 minutes to seal the container. The flowers are incubated for three days at 21 ° C. After treatment, the flowers are evaluated for two additional days for the incidence and severity of disease of the flower petals. Application of a treatment with 1 mg / L by means of sublimation results in a 0% incidence. Rose petals after treatment with Compound A have no disease incidence, preserving the white color, and no drop of petals. The results presented in Table 14 show good antimicrobial activity against infection of white roses by Botrytis cinerea, and that an increase in the volatilization rate by sublimation resulted in greater disease control. Table 14. Incidence and severity Botrytis cinerea based on infection in white rose petals and sepals after a volatile three-day treatment of Compound A at 21 ° C, and two more days at 21 ° C. * Severity Rating 0 = No disease 1 = Darkening and minor lesions on the sepals and petals 2 = Darkening, petals covered with fungal spores 3 = Darkening, petals covered with fungal spores, some drop of petals 4 = Darkening, petals covered with fungal spores, some aborted flowers Example 16
[109] To test the effect of Compound 10 (Figure 1) on vegetables, batter, onion and pumpkin were obtained from a local store and the surface was sterilized with 0.825% NaOCI. The potato slice or two onion leaves were placed in a sterile Petri dish, while whole pumpkin was placed in a sterile 2.6 L Snapwarede container (Model No. 109842). Each potato slice was inoculated with 20 pL of 1 x 105 spores / mL of Fusarium sambucínum, while onions were inoculated with 20 pL of 1 x 106 spores / mL of Botrytis cinerea. For pumpkin inoculation, a small nucleus was removed and a mycelial plug of Phytophthora capsid was inserted and covered with the nucleus. Compound 10 was diluted in acetone and added to a 42.5 mm Whatman No. 1 filter disc (Cat. No. 1001- 042), attached to the inside of the lid at a rate to achieve an aerial concentration end of 10 mg / L. The acetone was allowed to evaporate for 5 minutes before sealing the plates with parafilm or closing the containers tightly. The vegetables were incubated at 21 ° C for 3 days and evaluated for mycelium growth, fungal rot and soggy appearance (mm in diameter) with the results summarized in Table 13. Compound 10 demonstrated good fungal control of three plant pathogens , using three different vegetable cultures in this in vivo assay. Table 15. Effect of Compound A on the growth control of fungi in potato, onion and pumpkin. Example 17
[110] To test the effect of Compound A on the control of bacterial pathogens from vegetables, potatoes, onions and carrots are cut into small cubes and the surface sterilized with 0.825% NaOCI and allowed to dry. Four small cubes (approximately 1 cm2) of each vegetable are placed in a sterile Petri dish. Each cube is inoculated with 25 mL of Pectobacterium carotovorum (bacterial concentration of OD 1.0, 600 nm). For determination of efficacy, Compound A is diluted in acetone and the appropriate volume to obtain a final aerial concentration of 50 mg / L is added to a 42.5 mm Whatman N ° 1 filter disc (N ° of Cat. 1001-042), attached to the inner side of the cover. The acetone is allowed to evaporate for five minutes before closing the plate and sealing it with parafilm. The vegetables are incubated at 10 ° C for four days. The results presented in Table 16 demonstrate antimicrobial activity against P. carotovorum in onion (log reduction of 2.14), carrot (log reduction of 0.29) and potato (log reduction of 0.84) in this in vivo analysis . Table 16. Effects of Compound A (50 mg / L) in reducing the growth of P. carotovorum in potatoes, onions and carrots. Example 18
0 = ausência de crescimento fúngico 1 = leve infecção (apenas visível dentro da ferida com microscópio) 2 = infecção moderada (crescimento visível no ponto de inoculação) 3 = alta infecção (cone de Botrytis com diâmetro > 1 cm) 4 = infecção extrema (> metade do comprimento da fruta)[111] In order to assess in vivo activity of Compound The volatile antimicrobial in fruit, a volatile bioassay is developed using strawberries, grapes and blueberries. Eight strawberries, sixteen grapes or thirty blueberries (per representative) are placed on a commercially relevant PET clamshell-type tray, with the end of the stem facing upwards for blueberries and grapes, and downwards for strawberries. A new wound is inoculated with 20 pL (strawberry and grape) or 10 pL (blueberry) of 1 x 10 6 per ml of spore suspension of Botrytis cinerea. The clamshell type trays are placed in an airtight 2.6 L Snapwarede container (Model No. 109842). A 42.5 mm WhatmanN ° 1 filter disc (Cat. No. 1001-042) is placed on a watch glass. Compound A is dissolved in acetone and added to the discs in a dose-dependent manner to produce a final aerial concentration of 0.4; 2 or 10 mg / L. The acetone is allowed to evaporate for five minutes. The containers are then closed with lids and placed for three days at 21 ° C. After storage, fruits are evaluated for disease incidence and severity (0 to 4) for an additional three days at 21 ° C, with results summarized in Table 17. The results demonstrate good volatile antimicrobial control of Botrytis cinerea in alive, with approximately 50% less incidence and severely less severity for strawberries, grapes and blueberries, after three days of useful life. Table 17. Effect of a three-day volatile treatment of Compound A (0.4; 2 or 10 mg / L) on the control of the incidence and severity of B. cinerea strawberry, grape and blueberry infection, during an evaluation period three-day post-treatment at 21 ° C. 0 = no fungal growth 1 = mild infection (only visible inside the wound with a microscope) 2 = moderate infection (visible growth at the inoculation point) 3 = high infection (Botrytis cone> 1 cm in diameter) 4 = extreme infection ( > half the length of the fruit) Example 19
[112] In order to evaluate the in vivo activity of volatile antimicrobial Compound A in fruits, a volatile bioassay is developed using orange fruit. Two oranges are placed inside a PET clamshell tray. Three new orange slits are inoculated with 30 pL of 1 x 10 6 per ml of spore suspension of Penicillium digitatum. The clamshell trays are placed in a hermetic 2.6 L Snapwarede container (Model No. 109842). A 42.5 mm Whatman N ° 1 filter disc (Cat. No. 1001- 042) is placed on a watch glass. Compound A is dissolved in acetone and added to the discs in a dose dependent manner, to produce a final aerial concentration of 2, 10 or 50 mg / L. The acetone is allowed to evaporate for five minutes. The containers are then closed with the lids and placed for three days at 21 ° C. After storage, fruits are evaluated for disease incidence (mm of rot diameter) and pathogenic sporulation (mm of diameter) on the fruit surface, for two additional days at 21 ° C, with the results summarized in Table 18 The results demonstrate good control of volatile antimicrobial in vivo of P. digitatum in inoculated orange, especially at rates above 10 mg / L. Table 18. Incidence and severity of Penicillium digitatum in oranges, as illustrated by soaked lesion and fungal spores on the fruit surface Example 20
[113] In order to assess In vivo activity of Volatile Antimicrobial Compound A in fruits, a volatile bioassay is developed using apple. Two apples are placed inside a PET clamshell tray. Three new slits per apple are inoculated with 30 pL of 1 x 106 per ml of spore suspension of Penicillium expansum. The clamshell trays are placed in a hermetic 2.6 L Snapwarede container (Model No. 109842). A 42.5 mm WhatmanN ° 1 filter disc (Cat. No. 1001-042) is placed on a watch glass. Compound A is dissolved in acetone and added to the discs in order to produce a final aerial concentration of 50 mg / L. The acetone is allowed to evaporate for five minutes. The containers are then closed with the lids and placed for three days at 21 ° C. After storage, the fruits are evaluated for disease incidence (mm of rot diameter) and pathogen sporulation (mm of diameter) on the fruit surface, for an additional three days at 21 ° C, with summary results in Table 19. The results demonstrate 100% volatile antimicrobial control in vivo of P. expansum apple mold up to three days after treatment. Table 19. Incidence and severity of Penicillium digitatum in apples, as illustrated by dark rot and fungal spores on the fruit surface Example 21
[114] In order to assess in vivo activity of volatile antimicrobial Compound B in fruits, a volatile bioassay is developed using orange. Two oranges per repetition are placed inside a clamshell type tray. Three new orange wounds are inoculated with 30 pL of 1 x 106 per ml of spore suspension of Penicillium digitatum. The clamshell trays are placed in a hermetic 2.6 L Snapwarede container (Model No. 109842). Powdered Compound B is introduced into the containers by a sublimation device (copper tube heated to 200 ° C with fan flow at 0.5 L / min), to obtain a final aerial concentration of 0.4; two; 10 or 50 mg / L. The containers are then closed with the lids and placed for three days at 21 ° C. After storage, the fruits are evaluated for disease incidence (mm of rot diameter) and pathogen sporulation (mm of diameter) on the fruit surface, for an additional three days at 21 ° C, with summary results in Table 20. The results demonstrate good volatile in vivo inhibition of P. digitatum in orange at rates of 0.4 mg / L and complete inhibition at 10 mg / L. Table 20. Incidence and severity of Penicillium digitatum in oranges, as illustrated by soaked lesion and fungal spores on the fruit surface after treatment with Compound B. Example 22
[115] To assess the in vivo activity of volatile antimicrobial Compound A (Figure 1) in fruits, a volatile bioassay is developed using apple, pear, orange, strawberry, grape and blueberry. Two apples, two oranges, two pears, eight strawberries, sixteen grapes or thirty blueberries (per representative, in duplicate) are placed in a clamshell type tray with the end of the stem facing upwards on all fruits, except strawberry (end of the stem facing down). A new wound is inoculated with 20 pL of 1 x 106 per ml of spore suspension of Penicillium expansum (apple and pear), 20 pL of 1 x 106 per ml of spore suspension of Penicillium digitatum (la-ranja) and 20 pL (strawberry and grape) or 10 pL (blueberry) of 1 x 106 per ml of Botrytis cinerea spore suspension. The clamshell type trays are placed in a 117 L Rubbermaid storage box (Cat. No. 2244) and the lids are closed. Compound A, dissolved in acetone, is pipetted onto a cotton strip, in which the acetone is allowed to evaporate for five minutes, and then introduced into the container by a sublimation device (copper tube heated to 200 ° C with fan flow at 0.5 L / min), to obtain a final aerial concentration of 10 mg / L. The containers are then kept for three days at 21 ° C. After the treatment, the fruits are kept for another three days at 21 ° C, then evaluated for disease incidence (mm browning diameter or soggy lesions) and pathogen sporulation (mm diameter) for apple, pear and orange, as well as incidence (%) and severity (0 to 4) of Botrytis cinerea disease for strawberry, grape and blueberry, with results summarized in Table 21. The results demonstrate good in vivo antimicrobial control of at least three fungal pathogens in at least six different hosts when applied as a volatile fungicide. Table 21: Effects of Compound A sublimation as reflected by incidence and severity of B.cínerea in strawberry, grape and blueberry, and severity in oranges, apples and pears, as represented by water-soaked lesions, browning and sporulation after a treatment of three days plus three days at 21 ° C. Example 23
[116] To compare the capacity of Compound A when actively volatilized by different mechanisms, an in vivo assay using strawberry is performed. Eight strawberries are placed on a clamshell tray with the stem tip down. A new wound is inoculated with 20 µl of 1 x 1 o5 per ml of Botrytis cinerea spore suspension. clamshell type tray is placed in a 2.6 L Snapware airtight container (Model No. 109842) and closed with the lids. Compound A is dissolved in acetone and volatilized through a 1.27 cm side door sealable by an ES-100-H SmartFog system (Reno, NV). Alternatively, Compound A, dissolved in acetone, is pipetted onto a cotton strip, in which the acetone is allowed to evaporate for five minutes, and then introduced into the container by a sublimation device (copper tube heated to 200 ° C with fan flow at 0.5 L / min), to obtain a final aerial concentration of 10 mg / L. The fruits are stored for three days at 21 ° C. After three days of treatment, the fruits are stored for another three days at 21 ° C and then evaluated for incidence (%) and severity of the disease (0 to 4). The results are summarized in Table 22 and demonstrate good antimicrobial activity against Botrytis cinerea in this in vivo analysis, indicating that Compound A is an effective volatile antimicrobial. Table 22. Effects of different methods of volatile application of Compound A as reflected by incidence and severity of gray mold on strawberry after a three-day treatment, plus an additional three-day period at 21 ° C. Example 24
Pedaços de material são cortados com as dimensões apropriadas para proporcionar uma concentração aérea final de 0,4; 2 ou 10 mg/L. Os recipientes são fechados e colocados por três dias a 21 °C. Após o tratamento, as frutas são armazenadas por mais dois dias a 21 °C e, em seguida, avaliadas quanto à incidência (%) e gravidade (0-4) de doença, com os resultados resu-midos na Tabela 23. Os resultados demonstram boa atividade antimicrobiana in vivo de Composto A contra Botrytis cinerea, com uma redução na incidência e gravidade em todas as taxas, de uma forma dependente de dose, e que o composto volátil pode ser libertado de materiais diferentes.[117] An in vivo assay is used to assess the ability of Compound A to volatilize from different materials and to control duck-gene fungi. Eight strawberries are placed on a clamshell type tray with the end facing down. A new wound is inoculated with 20 µl of 1 x 106 per ml of Botrytis cinerea spore suspension. The clamshell type trays are then placed in a 2.6 L Snapware airtight container (Model No. 109842). Compound A is dissolved in acetone and then sprayed evenly on cellulose paper and Tyvek® fabric at a rate of 200 mg / m2 The acetone is allowed to evaporate. Likewise, Compound A is dissolved in propylene glycol and sprayed evenly on cellulose paper and Tyvek® fabric. No evaporation is attempted in this case. Table 23. Effects of different films and subsequent release of Compound A on the incidence and severity of Botrytis cinerea in strawberries, after a three-day treatment and an additional two-day storage at 21 ° C. Pieces of material are cut to the appropriate dimensions to provide a final aerial concentration of 0.4; 2 or 10 mg / L. The containers are closed and placed for three days at 21 ° C. After treatment, the fruits are stored for another two days at 21 ° C and then evaluated for disease incidence (%) and severity (0-4), with the results summarized in Table 23. The results demonstrate good in vivo antimicrobial activity of Compound A against Botrytis cinerea, with a reduction in incidence and severity at all rates, in a dose-dependent manner, and that the volatile compound can be released from different materials. Example 25
[118] An in vivo assay is used to assess the ability of compound A to volatilize different materials and control pathogenic fungi. Eight strawberries are placed on a clamshell tray with the stem end facing down. A new wound is inoculated with 20 µl of 1 x 106 per ml of Botrytis cinerea spore suspension. The clamshell type trays are then placed in a 2.6 L Snapware airtight container (Model No. 109842). As a substrate for Compound A, a 42.5 mm Whatman No. 1 filter disc (Cat. No. 1001-042) placed on a watch glass or 10 cm2 pieces of cardboard normally used for packaging strawberries. Compound A is dissolved in acetone and pierced on the disk or painted on the cardboard at a rate to obtain a final aerial concentration of 0.4; 2 or 10 mg / L. The acetone is allowed to evaporate for five minutes. The containers are closed and placed for three days at 21 ° C. After treatment, the fruits are stored for another two days at 21 ° C and then evaluated for disease incidence (%) and severity (0-4), with the results summarized in Table 24. The results demonstrate good in vivo antimicrobial activity of compound A against Botrytis cinerea, with a reduction in incidence and severity at all rates, in a dose-dependent manner, and that the volatile compound can be released from different materials. Table 24. Effects of different films and subsequent release of Compound A on the incidence and severity of Botrytis cinerea in strawberries, after a three-day treatment and an additional two-day storage at 21 ° C. Example 26
Tabela 25. Efeitos de diferentes materiais sobre a liberação volátil de Com- posto A e a subsequente inibição in vitro(CIM) de Botrytis cinerea.[119] An in vitro assay is used to assess the ability of Compound A (Figure 1) to volatilize from different materials and control fungal growth. PTFE Coated Fiberglass (8577K81), Fiberglass (8816k1), Silica (8799K3), Aramid and Fiberglass (8821K4), Vinyl Coated Polyester (8843K31), Acrylic Coated Fiberglass (8838K2), Fiber Glass Coated with Silicone (87815K1), PTFE (8577K81), Aramid (McMaster-Carr, Santa Fe Springs, CA-1206T1), PCR Polyethylene sealing film, Cellulose {Whatman No. 1, Cat. No. 1001- 0155) and Cardboard are cut into 15 mm diameter discs. 12-well microtiter plates (6.5 ml volume per well) are used for the in vitro inhibition assay for volatile antimicrobial compounds. A 3 ml volume of Potato Dextrose Agar (ADB) with total concentration is added to each well. After cooling, 1 pL of 1 x 105 per ml of Botrytis cinerea spore suspension is pipetted at a point in the center of the agar. The various materials are placed, in duplicate, under the underside of a PCR polyethylene plate sealing film. For the determination of the minimum inhibitory concentration (MIC), compounds are diluted in acetone and the appropriate amount of compounds is added to the materials in a dose dependent manner to reach a final air concentration of 35.7 to 0.03 mg / L. The acetone is allowed to evaporate for 5 minutes. The air space around the inoculum of Botrytis cinerea is then sealed inside the well by the film with the adherent disk that contains the fungicide. The plates are inverted, placed on the treated discs and sealed to prevent any portion of the chemical from discharging from the disc and falling onto the inoculated agar. After three days of storage at 23 ° C, cultures are evaluated for percentage growth in relation to control, based on the measurement of the diameter of fungal colonies. The experimental results are summarized in Table 25. The results indicate that Compound A can volatilize from numerous materials to inhibit growth in vitrode Botrytis cinerea with similar levels of control. Table 25. Effects of different materials on the volatile release of Compound A and the subsequent in vitro inhibition (MIC) of Botrytis cinerea. Table 25. Effects of different materials on the volatile release of Compound A and the subsequent in vitro inhibition (MIC) of Botrytis cinerea . Example 27
[120] An in vivo assay is used to assess the ability of Compound A to control the growth of fungi in seeds. Grains consisting of corn, wheat, rice, rye, millet and barley are sterilized on the surface with 0.825% NaOCI for 1 minute and washed slightly three times with sterile distilled water. The grains are inoculated by immersing them in 1 x 106 spores / mL of Aspergillus brasiliensis for 1 minute. The excess inoculum is removed with sterile paper towels before plating five seeds in a Petri dish containing 25 pL of ADB. For the determination of effectiveness, Compound A is diluted in acetone and added to 42.5 mm Whatman No. 1 filter discs (Cat. No. 1001-042) attached to the inside of the lid in a dose-dependent manner, for achieve a final aerial concentration of 0.4; 2 or 10 mg / L. The acetone is allowed to evaporate for five minutes before closing the plate and sealing it with parafilm. The plates are incubated at 23 ° C for three days. After storage, the grains are evaluated for the diameter of mycelium colonies (mm), with results summarized in Table 26. The results demonstrate 100% control of Aspergillus brasiliensis in this in vivo analysis. Table 26. Effect of an aerial treatment with 10 mg / L of Compound A in controlling the growth of Aspergillus brasiliensis in grains. Example 28
* Classificação de Gravidade 0 = Nenhuma doença 1 = Escurecimento e pequenas lesões nas sépalas ou pétalas 2 = Escurecimento, pétalas cobertas com esporos de fungos 3 = Escurecimento, pétalas cobertas com esporos de fungos, queda de algumas pétalas 4 = Escurecimento, pétalas cobertas com esporos de fungos, algumas flores abortadas[121] To evaluate a combined treatment of Compound A with 1-methylcyclopropene (1-MCP), an in vivo experiment is performed on white roses. Five white roses are placed in an 800 mL jar containing 200 mL of a common commercial flower preservative. Three jugs are then placed in a 117 L Rubbermaid storage box (Cat. No. 2244). Two small fans are placed at the opposite ends of the container to assist in the distribution of the two volatile products. A 500 ppb v / v treatment of 1-MCP is applied (AgroFresh, Springhouse, PA) for 24 hours at 21 ° C. After 1-MCP treatment is complete, the containers are evacuated and powdered Compound A is applied in a dose-dependent manner to achieve a final air concentration of 0.2; 0.04 or 0.008 mg / L, with a sublimation device (copper tube heated to 200 ° C with fan flow at 0.5 L / min), with the end of the tube penetrating through a side door of 1, 27 cm in the container, which is sealed immediately after application. The flowers are incubated for three days at 21 ° C. After treatment, the flowers are evaluated for another seven days at 21 ° C in relation to the incidence and severity of disease of the flower petals. The results presented in Table 27 show good antimicrobial activity against infection of white roses by Botrytis cinerea, and that the increase in the volatilization rate by sublimation resulted in greater control of the disease. Treatment with 1-MCP also reduced the drop of petals as reflected by the severity scores. Table 27: Incidence and severity Botrytis cinerea based on infection of white rose petals and petals after a 24-hour treatment with 1-MCP, followed by a volatile three-day treatment with Compound A at 21 ° C, and an additional five-day treatment at 21 ° C * Severity Rating 0 = No disease 1 = Darkening and minor lesions on the sepals or petals 2 = Darkening, petals covered with fungal spores 3 = Darkening, petals covered with fungal spores, drop of some petals 4 = Darkening, petals covered with fungal spores, some aborted flowers Example 29
Classificação por Pontuação de Cores 0 = Verde, brócolis com aparência regular 1 = Poucos pontos verde-claros 2 = Pontos verde-claros e amarelos 3 = Verde-claro, amarelo e alguns marrons 4 = Principalmente amarelo e marrom[122] To evaluate a combined treatment of Compound A with 1-methylcyclopropene (1-MCP), an in vivo experiment on broccoli is performed. Broccoli flowers are inoculated with 1 x 106 spores / mL of Alternaria. alternata and then placed in a 117 L Rubbermaid storage box (Cat. No. 2244), with two small fans placed at opposite ends of the container. A 500 ppb v / v treatment of 1 -MCP is applied (AgroFresh, Springhouse, PA) for 24 hours at 1 ° C. After the 1-MCP treatment is completed, broccoli florets are removed and placed in a 2.6 L Snapwarede airtight container (Model No. 109842). Powdered Compound A is applied in a dose-dependent manner to achieve a final air concentration of 2 or 0.4 mg / L, with a sublimation device (copper tube heated to 200 ° C with fan flow at 0.5 L / min), with the end of the tube penetrating through a side door of 1.27 cm in the container, which is sealed immediately after application. The florets are incubated for five days at 10 ° C or three days at 21 ° C, then evaluated for another five days at 21 ° C for the incidence and severity of the disease. The results presented in Table 28 show good antimicrobial activity against infection by Alternaria alternata. Table 28. Effects of Compound A and 1-MCP on rot control and broccoli ripening by Alternaria, respectively, five or three days of treatment at 10 or 21 ° C, with two more days at 21 ° C Color Score Classification 0 = Green, regular looking broccoli 1 = Few light green dots 2 = Light green and yellow dots 3 = Light green, yellow and some brown 4 = Mainly yellow and brown Example 30
.[123] To evaluate a combined treatment of Compound A with 1-methylcyclopropene (1-MCP), an in vivo experiment on tomatoes is performed. Each tomato fruit is wounded three times and inoculated with 1 x 106 spores / mL of Alternaria alternata and then placed in a 117 L Rubbermaid storage box (Cat. No. 2244), with two small fans placed in opposite ends of the container. A 500 ppb v / v treatment of 1-MCP is applied (AgroFresh, Springhouse, PA) for 24 hours at 1 ° C. After 1-MCP treatment is completed, tomatoes are removed and placed in 2.6 L Snapwarede airtight containers (Model No. 109842). Powdered Compound A is applied in a dose-dependent manner to achieve a final air concentration of 2 or 0.4 mg / L, with a sublimation device (copper tube heated to 200 ° C with fan flow at 0.5 L / min), with the end of the tube penetrating through a side door of 1.27 cm in the container, which is sealed immediately after application. The tomatoes are incubated for three days at 21 ° C, then evaluated for another three days at 21 ° C for the incidence and severity of the disease. The results presented in Table 29 show good antimicrobial activity against tomato infection by Alternaria alternata. Table 29: Effects of Compound A and 1-MCP on rot control in tomatoes by Alternaria, treatment for three days at 21 ° C, with another three days at 21 ° C . Example 31
[124] To assess the in vivo activity of volatile antimicrobial Compounds A and B (Figure 1) in fruits, a volatile bioassay is developed using apple, pear, orange, strawberry, grape and blueberry. Two apples, two oranges, two pears, eight strawberries, sixteen grapes or thirty blueberries (per representative, in duplicate) are placed on a clamshell tray with the end of the stem facing upwards on all fruits except strawberry (end of the stem) facing down). A new wound is inoculated with 20 pL of 1 x 106 per ml of spore suspension of Penicillium expansum (apple and pear), 20 pL of 1 x 106 per ml of spore suspension of Penicillium digitatum (orange) and 20 pL (strawberry) and grape) or 10 pL (blueberry) of 1 x 106 per ml of Botrytis cinerea spore suspension. Clamshell type trays are placed inside a 117 L Rubbermaid storage box (Cat. No. 2244) and the lids closed. Powdered compounds A and B are introduced into the containers by a sublimation device (copper tube heated to 200 ° C with fan flow at 0.5 L / min), to obtain a final aerial concentration of 1 mg / L. The containers are then kept for three days at 21 ° C. After treatment, the fruits are kept for another three days at 21 ° C, then evaluated for disease incidence (mm of browning diameter or soaked lesions) and pathogen sporulation (mm of diameter) for apples, pears and orange, as well as incidence (%) and severity (0 to 4) of Botrytis cinerea disease for strawberry, grape and blueberry, with results summarized in Table 30. The results demonstrate 100% in vivo antimicrobial control of B. cinerea and P digitatum by both Compounds A and B in different hosts, when applied as a volatile fungicide. Table 30. Effects of sublimation of Compounds A and B, as reflected by the incidence and severity of B.cinerea in strawberries, grapes and blueberries, and severity in oranges, apples and pears, as illustrated by soggy lesions, browning and sporulation after a three-day treatment, three additional days at 21 ° C. Example 32
[125] In order to assess the activity of Compound A as a contact fungicide, an in vitro test is developed. A Petri dish 6 cm in diameter is used. Compound A is altered in Potato Dextrose Agar (ADB) with total concentration to obtain a final solution concentration of 10; two; 0.4 or 0.08 mg / L, and a volume of 15 ml of solution is added to each plate. After cooling, 1 pL of 1 x 105 per ml of spore suspension of Penicillium expansum or Penicillium digitatum is pipetted into a central point on the agar.
[126] The plates are sealed with a parafilm and placed in an incubator maintained at 23 ° C. After three days of storage, cultures are evaluated for percentage growth in relation to control, based on the measurement of the diameter of fungal colonies. The experimental results are summarized in Table 31. The results indicate that Compound A has activity as a contact fungicide in this in vitro assay against plant fungal pathogens. Table 31. The MIC in vitropara for Compound 10 as contact fungicide for the inhibition of the mycelial growth of Penicillium expansum and Penicillium digitatum. Example 33
[127] In order to evaluate the activity of compound 10 (Figure 1) as a spray contact fungicide, an in vivo assay was developed. Two apples or two oranges (per representative, in duplicate) were placed on a clamshelle type tray, three new wounds, close to the equatorial region of each fruit. Compound 10 was dissolved in water to obtain a final concentration of treatment solution of 250, 50 or 10 mg / L. The fruits were dipped in a compound 10 solution for 1 minute and allowed to dry for 1 hour. Wounds were then inoculated on the fruits with 30 pL of 1 x 106 per ml of spore suspension of Penicillium ex pansum (apple) or spore suspension of Penicillium digitatum (orange). The clamshell trays were then placed in an airtight 2.6 L Snapwarede container (Model No. 109842) and incubated for three days at 21 ° C. After treatment, the fruits were kept for another three days at 21 ° C and then evaluated for disease incidence (mm diameter of browning or soaked lesions) and pathogen sporulation (mm diameter), with results summarized in Table 30. The results demonstrate good in vivo antimicrobial control of two fungal pathogens in two different hosts when applied as a contact fungicide. Table 32. In vivo MIC for Compound A as contact fungicide to control Penicillium digitatum and Penicillium expansum in oranges and apples, respectively. Example 34
[128] In order to assess the activity of Compound A as a volatile fungicide, an in vitro test was developed to assess spore germination. Two ml of agar in water is poured into 3.5 cm petri dishes. Compound A is dissolved in acetone, to obtain a final concentration of treatment solution of 0.14; 0.07 or 0.035 mg / L. The plates are inoculated with 1 pL of 1 x 106 per ml of spore suspension of Botrytis cinerea and Penicillium expansum. The plates are incubated for one day at 0 ° C, five days at 0 ° C or five days at 0 ° C, one or two additional days at 21 ° C. At each time point, plaques are removed and 100 spores are counted for germination percent, where germination is defined as a germ tube that extends a greater distance than the spore length. The results are summarized in Table 33. In all three treatment concentrations and temperature regimes, Compound A completely inhibits germination of the spores of pathogenic fungi tested. Table 33. Percent germination of Botrytis cinerea and Penicillium expansum spores in response to a volatile treatment with compound 10 under four different temperature regimes. Example 35
a Germinação de esporos determinada após 24 h de tratamento b Germinação de esporos determinada após mais 24 h após a remoção do tratamento c Crescimento micelial percentual 3 d após a transferência de inóculo para limpar placas de ADB[129] In order to assess the activity of Compound A as a volatile fungicide, an in vitro assay is developed to assess spore germination. 3.5 cm petri dishes are filled with 2 ml of agar in water. After cooling, 1 pl of 1 x 105 per ml of Botrytis cinerea spore suspension is pipetted at a point in the center of the plate. Table 34. Spore germination and subsequent mycelial growth after transfer to Botrytis cinerea new medium in response to a volatile treatment of Compound A. a Spore germination determined after 24 h of treatment b Spore germination determined after an additional 24 h after treatment removal c Percent mycelial growth 3 d after inoculum transfer to clean ADB plates
[130] Plates are inoculated immediately before volatile fungicide treatment. A Whatman No. 1 filter disc (Cat. No. 1001-0155) is placed in duplicate under the underside of a plate cover. For the determination of the minimum inhibitory concentration (MIC), compounds are diluted in acetone and the appropriate amount of compounds is added to discs in a dose dependent manner to reach a final aerial concentration of 142.9 to 0.07 mg / L. The acetone is allowed to evaporate for five minutes and then covers are placed on plates and sealed with parafilm. After 24 hours of storage at 23 ° C, 100 spores are counted for percent germination, where germination is defined as a germ tube that extends a greater distance than the spore length. After counting, the treatment is removed and the plates are sealed again. After an additional 24 hours, 100 spores are counted again. Buffers are then transferred to a clean plate containing full concentration ADB and left under incubation at 23 ° C for another three days. After incubation, mycelial growth (mm in diameter) is determined and summarized in Table 34. After 24 hours, 100% of the control spores germinated at the same time that all rates of Compound A resulted in 100% inhibition of germination in this volatile in vitro assay. These results show that compound A has a fungicidal effect, as opposed to a fungistatic effect, so that treated spores do not germinate and grow like mycelia, even after the compound has been removed.

权利要求:
Claims (12)
[0001]
em que A e D juntamente com os átomos de carbono aos quais estão ligados formam um anel fundido de 5, 6 ou 7 membros que pode ser substituído por Ci-6-alquila, Ci-6-alcóxi, hidróxi, halogênio, nitro, nitrila, amino, amino substituído por um ou mais grupos Ci-6-alquila, carbóxi, acila, arilóxi, carbona- mido, carbonamido substituído por Ci-6-alquila, sulfonamido ou trifluormetila, ou o anel fundido pode ligar dois anéis oxaborol; X é um grupo -CR7R8, em que R7 e R8 são cada um, independente-mente, hidrogênio, Ci-e-alquila, nitrila, nitro, arila, aralquila ou R7 e R8 junta-mente com o átomo de carbono ao qual estão ligados formam um anel alicí- clico; e R6 é hidrogênio, Ci-ie-alquila, Ci-ie-alquila substituída por Ci-6-alcóxi, Ci-6-alquiltio, hidróxi, amino, amino substituído por Ci-is-alquila, carbóxi, arila, arilóxi, carbonamido, carbonamido substituído por Ci-e-alquila, arila ou aralquila, aralquila, arila, heteroarila, cicloalquila, Ci-i8-alquilenoamino, Ci-ie-al- quilenoamino substituído por fenila, Ci-6-alcóxi ou Ci-6-alquiltio, carbonilalqui-lenoamino ou um radical de fórmula (V): em que A, D e X são como aqui definidos antes, exceto para borono- ftalida; e seus sais agricolamente aceitáveis; e contatar uma carne, planta ou parte de plantas com uma quantidade eficaz do composto antimicrobiano volátil em forma gasosa.1. Method of using a volatile antimicrobial compound against pathogens that affect meats, plants or parts of plants, CA-RACTERIZED by the fact that it comprises supplying in gaseous form a volatile antimicrobial compound of formula (IV): where A and D together with the carbon atoms to which they are attached form a 5, 6 or 7-membered fused ring that can be replaced by C1-6-alkyl, C1-6-alkoxy, hydroxy, halogen, nitro, nitrile , amino, amino substituted by one or more C1-6-alkyl, carboxy, acyl, aryloxy, carbonamido, C1-6-alkyl substituted, sulfonamido or trifluoromethyl carbonamido, or the fused ring can link two oxaborol rings; X is a -CR7R8 group, where R7 and R8 are each, independently, hydrogen, Ci-e-alkyl, nitrile, nitro, aryl, aralkyl or R7 and R8 together with the carbon atom to which they are linked form an alicyclic ring; and R6 is hydrogen, Ci-ie-alkyl, Ci-ie-alkyl substituted by Ci-6-alkoxy, Ci-6-alkylthio, hydroxy, amino, amino substituted by Ci-is-alkyl, carboxy, aryl, aryloxy, carbonamido , carbonamido substituted by Ci-e-alkyl, aryl or aralkyl, aralkyl, aryl, heteroaryl, cycloalkyl, Ci-i8-alkyleneamino, Ci-ie-alkenoamino substituted by phenyl, Ci-6-alkoxy or Ci-6-alkylthio , carbonylalkyl-lenoamino or a radical of formula (V): where A, D and X are as defined herein, except for boronaphthalide; and its agriculturally acceptable salts; and contacting a meat, plant or part of plants with an effective amount of the volatile antimicrobial compound in gaseous form.
[0002]
2. Method according to claim 1, CHARACTERIZED by the fact that the pathogen is selected from the group consisting of Acremonium spp., Albugospp., Alternaria spp., Ascochytaspp., Aspergillus spp., Botryodiplodia spp., Botryaspheria spp ., Botrytis spp., Byssochlamys spp., Candidaspp., Cephalosporium spp., Ceratocystis spp., Cercospora spp., Chalara spp., Cladosporium spp., Colletotrichum spp., Cryptosporiopsis spp., Cylindrocarpon spp. Spp., Didymella spp., Dipplodia spp., Dothiorellaspp., Elsinoespp., Fusariumspp., Geotrichum spp., Gloeosporium spp., Glomerella spp., Helminthosporium spp., Khusicia spp., Lasiodiplodia spp., Macrophoma spp., Macrophoma spp. Macrophomina spp. Microdochium spp., Monilinia spp., Monilochaethes spp., Mucorspp., Mycocentrospora spp., Mycosphaerella spp., Nectria spp. Neofabraea spp., Nigrospora spp., Penicillium spp., Peronophythora spp., Peronospora spp., Pestalatiopsis spp., Pezicula spp., Phacidiopycnis spp., Phoma spp., Phomopsis spp., Phyllostictapp. Polyscytalum spp., Pseudocercospora spp., Pyricularia spp., Pythiumspp., Rhizoctoniaspp., Rhizopusspp., Sclerotiumspp., Sclerotinia spp., Septoria spp., Sphaceloma spp., Sphaeropsis spp., Stem- spyll. ., Thielaviopsis spp., Thyronectria spp., Trachysphacra spp., Uromyces spp., Ustilagospp., Venturiaspp., And Verlicillium spp.
[0003]
3. Method according to claim 1, CHARACTERIZED by the fact that the pathogen is selected from the group consisting of Er-winiaspp., Pantoeaspp., Pectobacterium spp., Pseudomonasspp., Ralstonia spp., Xanthomonas spp .; Salmonella spp., Escherichia spp., Lactobacillus spp., Leuconostoc spp., Listeria spp., Shigella spp., Staphylococcus spp., Candida spp., Debaryomyces spp., Bacillus spp., Campylobacter spp., Clavi- bacter spp., Clostridium spp., Cryptosporidium spp., Giardia spp., Vibrio spp., Xanthomonas spp., And Yersinia spp.
[0004]
4. Method, according to claim 1, CHARACTERIZED by the fact that the method comprises a treatment selected from the group consisting of treatment during packaging in the field, treatment during palletization or after palletization, on open pallets or on packed pallets, in tents , treatment in the box with or without coating, in marine containers, trucks or other types of containers used during transport, and treatment during storage.
[0005]
5. Method, according to claim 1, CHARACTERIZED by the fact that the plants or parts of plants are selected from the group consisting of corn, wheat, cotton, rice, soy and canola.
[0006]
6. Method, according to claim 1, CHARACTERIZED by the fact that the plants or parts of plants are selected from the group consisting of fruits, vegetables, nurseries, peat and ornamental plants.
[0007]
7. Method, according to claim 6, CHARACTERIZED by the fact that the fruit is selected from the group consisting of bananas, pineapples, citruses, grapes, watermelon, cantaloupe, melon and other melons, apple, peach, pear, cherry, kiwi, mango, nectarine, guava, papaya, persimmon, pomegranate, avocado, fig and berries.
[0008]
8. Method, according to claim 7, CHARACTERIZED by the fact that wild fruits are selected from the group consisting of strawberry, blueberry, raspberry and blackberry.
[0009]
9. Method, according to claim 7, CHARACTERIZED by the fact that the citrus is selected from the group consisting of oranges, lemon, lime and grapefruit.
[0010]
10. Method according to claim 1, CHARACTERIZED by the fact that contacting the meat, plant or part of plants with an effective amount of the volatile antimicrobial compound in gaseous form includes spraying, misting, thermal or non-thermal nebulization, spraying, treatment gas and their combinations.
[0011]
11. Method according to claim 10, CHARACTERIZED by the fact that the gas treatment is selected from the group consisting of release from a sachet, release from a synthetic or natural film, release from a coating or other packaging materials, release from dust, release from a gas release generator, release using a cylinder of compressed or uncompressed gas, release from a droplet inside a box and its combinations.
[0012]
12. Method, according to claim 1, CHARACTERIZED by the fact that the volatile antimicrobial compound has a structure of

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法律状态:
2014-12-02| B03A| Publication of an application: publication of a patent application or of a certificate of addition of invention|

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2017-02-14| B25A| Requested transfer of rights approved|Owner name: AGROFRESH INC. (US) |

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2017-03-28| B06F| Objections, documents and/or translations needed after an examination request according art. 34 industrial property law|

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2019-07-16| B07A| Technical examination (opinion): publication of technical examination (opinion)|

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2019-12-03| B06A| Notification to applicant to reply to the report for non-patentability or inadequacy of the application according art. 36 industrial patent law|

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2020-04-07| B09A| Decision: intention to grant|

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2020-10-27| B16A| Patent or certificate of addition of invention granted|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 29/01/2014, OBSERVADAS AS CONDICOES LEGAIS. |

优先权:

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申请号 | 申请日 | 专利标题

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US201361758313P| true| 2013-01-30|2013-01-30|

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US61/758,313|2013-01-30|

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