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    • 专利摘要:
    This disclosure describes novel 15-deoxy-16-hydroxy-16-substituted prostanoic acids and congeners thereof having utility as bronchodilators as hypotensive agents, and as agents for the control of excessive gastric secretion.
    公开号:SU873877A3
    申请号:SU772503854
    申请日:1977-07-19
    公开日:1981-10-15
    发明作者:Бронер Флойд(Младший) Мидлтон；Винсент Грудзинскас Чарльз；Мей Лай Чен Сау
    申请人:Американ Цианамид Компани(Фирма)；
    IPC主号:
    专利说明:

    5 furan. And 50 ml of water. After dissolving, toluene is added and the mixture is evaporated. The remaining oil is chromatographed on silica gel with hexane, which is gradually enriched with benzene, then with acetone, and 16 g of oil are obtained. Example 4. Obtaining 4-oxo-1-iodine-trans-1-oKTeiia. To a stirred suspension of 6.15 g of pyridinium chlorochromate in 20 Mji of methylene chloride was added 450 mg of sodium acetate. After 5 minutes, a solution of 3.65 g of 4-OXY-1-iodo-trans-1-octene in 15 ml of methylene chloride is added at one time. The dark mixture is stirred at room temperature for 75 minutes, diluted with 50 ml of ether and decanted. The solid slurry is re-washed with ether and decanted. The combined solutions are percolated through florisil. The solution is evaporated and an orange oil is obtained. Example 5. Obtaining 4-hydroxy-4-VINIL-1-iodine-trans-1-octene. To a mixed solution of 7.8 ml of vinyl magnesium chloride (2.3 M in tetrahydrofuran) was added 15 minutes a solution of 3.55 g of 4-oxo-1-iodo-trans-1-rctene in 20 ml of tetrahydrofuran. After the addition, the solution is stirred for 30 min. (-20) - (- 15) ° C. The aqueous phase is separated and extracted with hexane. The combined hexane extracts are washed with water and brine. The solution is dried with magnesium sulfate and evaporated. The residue is chromatographed on silica gel on a dry column with benzene to give a liquid. Example 6. Obtaining 4-trime tilsiloxy-4-Vilin-1-iodo-trans-1 -. -oktena To a stirred solution of 456 mg of 4-hydroxy-4-vinyl-1-iodo-trans-1-octene and 320 mg of imidazop in 1 ml of dimethylformamide were added 0.23 ml of chloromethylsilane for 3 minutes. The mixture was stirred at room temperature for 22 hours and separated with a mixture of cold hexane and water. The hexane layer was washed twice with water and the brine was dried with magnesium sulfate, evaporated and an oil was obtained. Example 7. Getting 9-Rcr-lli, I 6-DIOXI-16-VYNIL-13-trans-Yrh stenovy acid. To a stirred solution of 555 mg of 4-trimethylsiloxy-4-vinyl-1-iodo-trans-1-octene in 2 ml of ether is added a solution of tert-butyl-acetate in p-tan (1.6 M) for 10 minutes at. The solution is stirred at -78-1.5 hours and at 30 minutes and quenched with 7 1-lithio-trans-alkene. In a flask, mix the mixture with 0.2 | 1-copper (1) -1-pentin, 0.7 ml of hexamethylphosphorus triamide and 2 ml of ether to obtain a clear solution. This solution is added IO min to a stirred solution of 1-lithio-trans-alkene at -78 ° C. The solution is stirred for 2 hours at -78 ° C, then it is treated with a solution of 580 mg of a 4- (trimethylsilfoxy) -2- (b-carbotrimethylsiloxyhexyl) -cyclopent-2-en-1-one in 3 ml of ether for 10 minutes. After holding for 10 minutes at - the solution is stirred for 1 hour at -40 to -50 ° C and at -35 to 1 hour. The solution is cooled until it is poured into 100 ml of an ammonium chloride solution and diluted with ether. The organic phase is separated, washed with water and dilute hydrochloric acid, filtered through diatomaceous earth, the filtrate is washed with water and brine, and dried with magnesium sulfate. After the solution has been quenched, crude bis-trimethylsilyl ether is obtained in the form of an oil. The oil is treated with a solution of IO ml of glacial acetic acid, 5 ml of tetrahydrofuran and 2.5 ml of water. The mixture is stirred at room temperature for 20 minutes and diluted with 50 ml of toluene. After evaporation at Z3-C under vacuum, the residue is chromatographed on silica gel with 1% acetic acid in ethyl acetate to give an oil. Example 8. Preparation of n-butylcycloceropyl ketone. To a highly stirred solution of 31.0 g of cyclopropanecarboxylic acid in 330 ml of ether. At 5-10 ° C, a solution of n-butyl lithium (748 mmol) in almost 750 ml of 2: 1 ether-hexane mixture is added. The resulting suspension is diluted with 300 ml of ether and stirred at room temperature for 2 hours and at reflux for 2 hours. The mixture is then cooled and poured into several portions of a mixture of ice and 4N. hydrochloric acid (1: 1). The ether phases are combined, washed with brine, sodium carbonate solution and again dissolved (Pom. The extract is dried with magnesium sulfate and evaporated. The residue is distilled and a liquid with a boiling point of 102-104 s / 80 mm Hg is obtained. Example 9. Preparation 4 -cyclopropyl-4-hydroxy-1-octane. A suspension of amalgamy prepared from 6.2 g of magnesium and 50 mg of mercury chloride (2) suspended in 60 ml of ether is added to the mixture of boiling under reflux and suspended in 60 ml of ether. , 4 g of n-butyl cyclopropyl ketone and 29.8 g of propargyl bromide in 65 ml of ether. After the reaction with those The mixture was cooled under reflux, where 30 min before and treated with 35 rui of saturated ammonium chloride solution. The mixture is then diluted with ether and filtered through celite. The filtrate is washed with brine, dried with potassium carbonate and evaporated. The residue is distilled and a liquid is obtained with temperature boiling point 93-94 ° C / 12 mm Hg.
    Example 10. Getting 4-cyclopropyl-4-trimethylsiloxy-I-octin. To a stirred solution, 27.8 g of 4-cyclopropyl-4-hydroxy-1-octin and 33.3 g of imidazole in 130 ml of dimethylformamide at 5 ° C are added 24 ml of chlorotrimethylsilane for 5 minutes. The solution is stirred at room temperature for 17 hours, then distributed in 600 ml of hexane and 250 ml of ice-water. The hexane phase is separated, washed with water and brine. The solution is dried with magnesium sulfate, evaporated and a liquid is obtained.
    Example 11. Obtaining 4-cyclopropyl-4-trimethylsiloxy-1- (tri-n-butylstannyl) -trans-1-octene. A stirred mixture of 23.8 g of 4-cyclopropyl-4-trimethylsiloxy-1-octin, 28 m of toi-n-butyltin hydride and 50 mg of azobisisobutyronitrile in a nitrogen atmosphere, heats to 85 C. After the developed exothermic reaction, the mixture is heated for 1 hour to 130c.
    The crude product is distilled off and a liquid is obtained.
    Examples 12-14. According to the method of Example 8, the following cyclopropylalkyl ketones given in c. Are obtained by the reaction of the corresponding alkyllithium with cyclopropanecarboxylic acid tab. one.
    Examples 15-18. By the reaction of vinyl lithium with the required carboxylic acid, the following vinyl ketones are obtained, as indicated in table. 2
    Examples 18 (a-d) -20..no the method of example 9 by the reaction of propargylmagnesium bromide with ketones from Table. 3 get the following 4-substituted-1-alkyne-4-oly.
    Examples 21-25. According to the method of example 10 are given in table. 4 4-substituted-1-alkyne-4-oly convert into their corresponding trimethylsilyl ethers.
    Examples 27-32. According to the method of example 11 by the reaction of tri-n-butyltin hydride with the precursor of 1-alkines from the table. 5 get the following 1 - (tri-n-butylstannyl) -4-substituted-4-trimethylsiloxy-trans-1-alkenes.
    EXAMPLE 33 Preparation of 9-oxo-1 1 oL, I 6-dioxy-1 6-cyclopropyl-5-cis, 1Z-trans-prostadiene acid. TO
    a stirred solution of 11.54 g of 4-cyclopropyl-4-tri-methylsiloxy-1 - {tri-n-butylstanyl) -trans-β-octene in IO ml of tetrahydrofuran is added at -78 ° C for 10 min. 9.1 ml of 2.4 M n-butyl lithium in hexane. The resulting solution was stirred at -1Q ° C for 10 minutes, at -40 ° C for 1 hour and at -40 to 40 minutes. A solution of 2.84 g is added to the stirred solution.
    pentynylmedium, 10.8 ml of tri-n-butylphosphine in 25 ml of ether. The resulting solution was stirred at -78 C for 2 h, then it was treated for 10 minutes with a solution of 6.03 g of 2- (b-trimethylsiloxycarbonyl r2) -cis-hexenyl-4-trimethylsiloxycyclopent-2-en-1-one (Table 6, link L) in 20 ml of ether. After 10 min, the solution is stirred at -50 to -40 ° C I h, then at -40
    up to 50 min The solution is cooled again to -50 ° C and poured into a stirred mixture of 600 ml of a saturated solution of ammonium chloride and 300 ml of ether; The organic phase is separated.
    and washed with dilute hydrochloric acid, water, and brine.
    The residue obtained after evaporation of the solvent was treated with 120 ml of glacial acetic acid, 60 ml of tetrahydrofuran and 30 ml of water, the mixture was stirred at room temperature for 30 minutes, diluted with 150 ml of toluene and evaporated. The residue is purified by chromatography on a dry silica gel column with 1% acetic acid in ethyl acetate to give an oil.
    Examples 34-49. 9-OKco-lldl, 16-dioxy-prostadiene or prostoic acids from the table. 6 get
    according to the method of example 38. In accordance with the described method, the starting 1- (tri-n-butylstannyl) -4-trimethylsiloxy-trans-1-alkenes from Table. 6 are treated with n-butyl lithium and the corresponding trans-1-alkenyl-lithium derivatives are obtained, which, after treatment with the penten-copper-tri-n-butylphosphine complex, give the corresponding trans-1-alkenecuprates, the latter are treated with 4-oxycyclopent-2-en-1 - it specified in tab. 6. The obtained trimethylsilyl esters of 9-oxo-1 loL, 16-bis (trimethylsiloxy) -prostadiene or prostoic acids are hydrolyzed by treatment with a mixture of acetic acid and tetrahydrofuran-water. Example 50 Preparation of 9d, 1I 16-trioxy-16-cyclopropyl-5-cis, 13-trans-prostadiene acid. To a stirred solution of 785 mg of 9-oxo-1IcL, 16-dioxy-16-cyclopropyl-5-cis, 13-trans-prostadiene acid (Example 33), 12 ml of tetrahydrofuran at -70 ° C are added 12 ml of 0.95 M perhydro-9 solution (L-borafenalyl lithium hydride in tetrahydrofuran. The solution is stirred at 30 minutes, heated to 0 ~ 15 minutes and treated with 0.6 ml of water. The mixture is distributed with ether and potassium carbonate solution. The aqueous phase is acidified with hydrochloric acid and extracted with ethyl acetate The extract is washed with water and brine, dried over magnesium sulfate and evaporated. The resulting residue is chromatographed Coziness on a silica gel column using 1% acetic acid in ethyl acetate gives 3–3 oil. Examples 51-67 Reduction of the 9-oxo derivatives listed in Table 7 with perhydro-9p-borafenalyl lithium hydride according to the method of example 50 gives the 9c1-hydroxy-prostadiene and prostane k-acids as listed in Table 7. Examples 68-75. Treatment of cyclopentenone-alkyl ethers from Table 9 with cuprate derivative 1- (tri-n-butylstanyl-A-cyclopropyl-4- trimethylsiloxy) -trans-1-octane (example 11) according to the method of example 33 or cuprate derivative 4-trimethylsiloxy-4-VINIL-I α-iod-trans-1-octene (Example 6) according to the procedure of Example 7, followed by the removal of the trimethylsilyl group according to the procedure of Example 33, gives the alkyl esters of 1b-substituted-16-hydroxy-prostanoic acids listed in Table. 8. Examples 76-83. Saponification of the alkyl esters of 16-substituted-16-hydroxyprostenoic acids from the table. 9 using 0.5 n. potassium hydroxide in methanol-water 10: 1 at room temperature for 24 hours, followed by acidification and extraction with ether gives 16-3 substituted 16-hydroxy-prostadiene or prostoic acids from the table. 9. Example 84. Preparation and separation, 11c6.1 6-trioxy-1 6-cyclopropyl-5-cis-13-trans-prostadiene acid and 9 | 3, llct, 16-trioxy-16-cyclopropyl-5-cis- 13-trans-prostadiene acid. To a displaced ice-cooled solution of 350 mg of 9-oxo-11-0,16-dioxy-16-cyclopropyl-5-cis, I 3-trans-prostadiene acid in 50 ml of ethanol, 408 mg of sodium borohydride are added in small portions over 1 minute. The mixture was stirred at room temperature for 1 min. For 1 hour. The bulk of the ethanol was distilled off, the residue was distributed with cold dilute hydrochloric acid and ethyl acetate. The organic phase is separated and washed with water and brine, dried over magnesium sulfate and evaporated. Remaining the current is chromatographed on silica gel to give an oil, first eluted with 8i, 1 lei, I 6-trioxy-1 6-cyclopropyl-5-cis-13-trans-prostadiene acid, (second eluate) oil 9cL, lldL, 16-trioxy-16 -cyclopropyl-5-cis, 13-trans-prostadiadiic acid Examples 85-103. Treatment of 9-oxo-prostaglandins from table. 10 sodium borohydride as described in Example 100, followed by chromatography. It gives 9dr-oKCH and 9 | b-oxy prostaglandins from tab. 10. Table 1
    n-propyl lithium
    12 13 n-Amillithium
    n-Hexylthium
    14
    Cyclopropyl n-propyl ketone
    n-amylcyclopropyl ketone
    Cyclopropyl n-hexyl ketone
    Example Carboxylic acid I Targeted alkyl vinyl ketone

    15i-Oil on acid-propyl vinyl ketone
    16n-Valerianova acid-Butylviiilketon
    17i-Kapronova acid-Amilvinilketoi
    18n-Anaitic acid-Hexylvinyl ketone
    Source ketone Target 4-substituted of example -1-alkyne-4-ol
    12 13 14 15 17 18
    Purposeful 4-trimethylsiloxy-1-alkyi
    4-Cyclopropyl-4-trimethylsiloxy 8a -1-heptin
    4-Cyclopropyl-4-trimethylsiloxy181 -1-nonin
    4-Cyclopropyl-4-trimethylsiloxy18s -1-decin
    18d
    4-Trimethylsiloxy-4-vinyl-I-heptin 4-Trimethylsiloxy-4-vinyl-1-nonin
    19 4-Trimethylsiloxy-4-vinyl-1.-detsin
    20
    Table 2
    .Ta 6 l and c a 3
    4-Cyclopropsh-1-4-hydroxy-1-heptin 4-Cyclopropyl-4-hydroxy-1-nonin 4-Cyclopropyl-4-hydroxy-1-detsin 4-OXI-4-VINIL-1-heptin 4-OXI-4- VINIL-1-nonin 4-OXI-4-VINIL-I-detsin
    Table 4
    27 28 29
    21 22 23
    30 31 32
    24 25 26
    27
    126
    34
    28
    126
    35
    29
    126
    36
    thirty
    126
    37
    31
    126
    38
    , 32
    126
    39
    Table 5
    1- (Tri-n-butylstanyl) -4-cyclopropyl-4-cyclopropyl-4-trimethylsiloxy-trans-1-heptene
    I- (Tri-n-butylstannyl) -4-cyclopropyl-4-trimethylsiloxy-trans-1-nonene
    1- (Tri-n-butylstanyl) -4-cyclo-, propyl-4-trimethylsiloxy-trans-1 decene
    1- (Trn-n-butylstannyl) -4-vinyl-4-trimethylsiloxy-trans-1-heptin
    1- (Tri-n-butylstannyl) -4-VINIL-4-trimethylsiloxy-trans-1-nonene
    1- (Tri-n-butylstannyl) -4-vinyl-4-trimethylsiloxy-trans-1-decene
    Table 6
    Let 9-OXO-1 let, 16-cyclopropyl-20-Hop-l3-transprostanic acid
    9-Oxy-Hi, 16-DIOXI-16-cyclopropyl-20-methyl-13-trans-prostanova acid
    9-Oxo-11 dl, 16-DIOXI-16-C1 1 clopropyl 20-ethyl-.13-trans-prostanoic acid
    9-Oxo-P cL, 16-dioxy-16-vinyl-20-nor-13-trans-prostoic acid
    9-Oxo-11 d, 16-dioxy-16-vinyl-20-methyl-13-trans-prostoic acid
    I
    9-Oxo-1 Iti-, 16-dioxy-16-VINIL-20-ETHIL-13-trans-prostoic acid
    40 126P
    41
    42 A28
    43 A29
    44 A30
    45 A31
    46 A32
    47А (according to the method
    example 7)
    48127
    49 12811
    49A 129
    49С 129А11
    49D 129B
    fd. 4-trimethylsiloxy-2- (6-karbotrimeti SSh1ox) -2-cissenil) -cyclopent-2-en-1-one
    Continued table. 6
    9-OKCO-I lot, 16-DIOXI-1 6-cyclopropyl-13-trans-prostoic acid
    9-oxo-1 let, I 6-dioxy-1 6-cyclopropyl-20-nor-5-cis-13-trans-prostadiene acid
    9-Oxo-1 Id, 16-dioxy-16-cyclopropyl-20-methyl-5-cis-13-trans-prostadiene acid
    9-Oxo-1 Idl, 1 6-dioxy-1 6-CYCLOPROPIL-20-ETHIL-5-CIS-13-trans-prostadiene acid
    9-OXO-1 IcL, 16-dioxy-16-VINIL-20-NOR-5-cis, 13-transprostacid acid
    9-OXO-1 let, 1 6-dioxy-1 6-vinyl-20-methyl-5-cis, 13-trans-prostadiene acid
    9-Oxo-1 l-d-, 1 6-dioxy-16- -VINIL-20-ETHIL-5-DIS, 13-trans-prostadiene acid
    9-Oxo-1 1 oL, 16-dioxy-1 6-VINIL-5-TsIS, I3-trans-prostadiene acid
    Methyl ester of 1-9-oxo-1 lot, 16-dioxy-16-vinyl-13-trans-prostoic acid
    Methyl ether 1-9-oxo-1LL, 16-dioxy-16-cyclopropyl-5-cy-13-trans-prostadiene acid
    9-Oxo-11 d, 16-dioxy-16-vinyl-5-cis-13-trans-2a, 2c-bis-homoprostadiene acid
     9-Oxo-1 Id, 16-dioxy-16-cyclopropyl-13-trans-3-oxa-prostanoic acid
    9-Oxo-1 1 el, 16-dioxy-1 6-vinyl-13-trans-3-oxa-prostanoic acid
    heck34 35
    36 37 38 39 40 41
    42 43
    44 45 46 47 7
    48 49
    49A
    Table 7
    9 d, 11 oL, 1 6-Trioxy-16-cyclopropyl-20-HOp-i 3-tr. An-prostoic acid 9o1., 1 lot /, 1 6-Trioxy-1 6-cyclopropyl-20-methyl-13 trans-prostova acid
    ., 1 I dl, 1 6-Trioxy-1 6-cyclopropyl-20-ethyl-13-trans-prostoic acid
    9c1 1 I cL, 1 6-Trioxy-16-vinyl-20-nor-13-trans-prostoic acid
    9A, 1 Id, 16-Trioxy-16-VINIL-20-methyl-13-trans-prostoic acid
    9A, I Id, 16-Trioxy-16-VINIL-20-ETHIL-13-trans-prostoic acid
    9d., 1 Id, 16-Trioxy-1.6-cyclopropyl-I3-trans-prostoic acid
    9d 1 Id, 16-Trioxy-16-cycloprog (il-20-nor-5-cis, 13-trans-prostadiene acid
    9c1., 1 Id, I 6-Trioxy-1 6-cyclo-11-propyl-20-methyl-5-cis, 13-trans-prostadiene acid
    .9d, 1 Id, 16-Trioxy-16-cyclopropyl-20-ETHIL-5-CISS, 13-trans-prostadiene acid
    9d, 11d, 6-Trioxy-16-vinyl-20-nor-5-cis, 13-trans-prostadiene acid
    9d, 11d, 1 6-Trioxy-16-Bif nyl-20-methyl-5-cis, I3-trans-prostadiene acid
    9bL, I Id, 16-Trioxy-16-VINIL-20-Etil-5-cis, 13-trans-prostadiene acid
    9oC 1 Id, 16-Trioxy-16-VINIL-5-CIS, 13-trans-prostadiene acid
    9A, 1 Id, 16-Trioxy-16-VINIL-13-transprostanic acid
    Methyl ester 1-9d, 11 d, 16-trioxy-16-VINIL-13-trans-prostoic acid
    Methyl ester 1-9oU 11 d, 16-trioxy-16-cyclopropyl-5-cis-13-trans-prostadiene acid
     Id, 16-Trioxy-1 6-vinyl-5-cis-13-trans-2a, 2c-bis-homoprostadic acid
    nineteen
    9b1, Ii, 16-Trioxy-1 6-cyclopropyl-5-cis, 13-trays-2a, 2c-bis-homoprostadienic acid
    9oL, P i, 16-Trioxycyclopropyl-1 3-trans-3-oxa-prostanoic acid
    9о1, Id ,, 16-Trioxi-16-vinyl-13-trans-3-oxycryte acid
    The original 1- (tri-Original alkyl ether-n-butylstanine cyclopentenone-4-trimethylsiloxy) -trans-1-alkene from example
    2- (6-Carbomethoxy-2-cis-hexenyl) cyclopent-2-en-1-one
    (US Patent No. 3873067)
    2- (b-carbomethoxy-2-cis-hexenyl) cyclopent-2-ene-1-one (US Patent No. 3,873,607)
    2- (b-Carbethoxyhexyl) -2-cyclopentenone (US Patent No. 3873607)
    2- (b-carbethoxyhexyl) -2-cyclopen genon (US Pat. No. 3,873,607)
    2- (b-Carbethoxy-5-thiagoxide) -2-cyclpentenone
    2- (b-Carbethoxy-5-thia-hexyl) -2-cyclopentenone
    (US Patent No. 3873607)
    2- (b-Carbethoxy-5-oxahexyl) -2-cyclopentenone (US Patent 3,873,607)
    2- (b-Carbethoxy-5-oxahexyl) -2-cyclopentenene (US patent No. 3873607)
    20
    8738.77 Continuation of the table. 7
    Table 8
    Targeted alkyl ester of 16-substituted-1-hydroxy-prostadiene or prostoic acid
    eth1-9-oxo-16-oxig
    -16-cyclopropyl-5-cis, 13-trans-prostadiene.
    Methyl-9-oxo-16-hydroxy-16-VINIL-5-CISS, 13-trans-prostadiene
    Ethyl 9-OXO-6-OXI-16-cyclopropyl-13-trans-prostanate
    Ethyl 9-OXO-16-OXI-16-vinyl-13-trans-prosteno
    X.
    Ethyl-9-oxo-16-hydroxy-16-vinyl-3-t and-13-trans-prostanate
    Ethyl-9-oxo-16-hydroxy-16-cyclopropyl-3-thia-13-trans-prostanate
    Ethyl 9-oxo-16-hydroxy-16 vinyl-3-oxa-13-transprostenoate
    Ethyl 9-oxo-16-hydroxy-16-cyclopropyl-3-oxa-13-trans-prostanate
    9eL // J, I 1 dL, 16-Trioxy-1 6-cyclopropyl-20-nor-1 3-trans-prostoic acid
    9ol // i, 1 Idl 16-Trioxy-1 6-cyclopropyl-20-methyl-13-trans-prostoic acid
    9oL / Ib, 11d, 16-Trioxy-16-cyclopropyl-20-ethyl-13-trans-prostoic acid
    9d / | i, 11 (1,16-Trioxy-16-vinyl-20-nor-13-trans-prostave acid
    9о1 / (Ь, I lot, 1 6-Trioxytvinyl-20-methyl-1 3-trans-prostanova Acid
    9d / (b, l1A, 16-Trioxy-16-vinyl-20-ethyl-13-trans-prostoic acid
    9A / tb, 114,16-Trioxy-16-cyclopropyl-1 3-trans-prostoic acid
    9dl / fb, 11 cL, 1 6-Trioxy-16-cyclopropyl-20-nor-5-cis, I3-trans-prostadiene acid
    9tl / ft, 1 Id /, 16-Trioxi-16-cyclopropyl-20-methyl-5-cis, 13-trans-prostadiene acid
    Table 9
    Table 10
    oic acid of General formula 1
    1 - OFl
    H (
    1-12 hydrogen or alkyl with
    R-, carbon by us,
    RA is alkyl with 2-7 carbon atoms;
    R is hydrogen, OXI-, trialkyl () siloxy or tetrahydropyranyl-2-hydroxy,
    -, e HE
    methylvinyl or cyclopropyl,
    group of formula C
    % n
    /
    H
    BUT.
    or
    But also
    Z - group - (СНо) (, -, cis-CHaCH CH (CH2) rt, -tCHj J SCH - or - (CH2) „OCH2, where n is an integer from 3 to 5, provided that if Z - (CH.i), SCHj, then Rj is hydrogen.
    权利要求:
    Claims (1)
    [1]
    Claim
    X is a group of the formula
    A method for the preparation of optically active or racemic derivatives of prostanoic acid of the general formula 1 'L.
    where R ^ is hydrogen or alkyl with 1-12 carbon atoms, is alkyl with 2-7 carbon atoms;
    R | - hydrogen, oxy-, trialkyl (C ^ -Cj) siloxy or tetrahydropyranyl-2-hydroxypropyl, or Q-, r ' he • 5 methyl vinyl or Y is a group of the formula but' ~
    R $ - vinyl, cyclopropyl,
    -C-, -CII /% o n he or -C / BUT Ή
    Ζ ~~ group - (CHtsis-CH 1 CH = CH (CH 2) h, - (CH ^ nSCH ^ or - (CH ^ ^ tsOSN where η - an integer from 3 to 5, with the proviso that if Ζ - ( CH ^) h SCHj, then R $ is hydrogen, in the case when the most general formula
    L or their salts, R-1 is hydrogen, so that the compound
    B d and R j. have the indicated carry out the removal of ether or where Z ( has the indicated meanings;
    R ^ is alkyl with 1-12 carbon atoms of the first kind; · - hydrogen, trialkyl (C ^ -C ^) siloxy or tetrahydropyryl nyl-2-hydroxy group, is reacted with lithium cuprate of the general formula I I I
    N
    L 5 n o ^ '(bi 3 ) 3
    Bg where R and RJ have the indicated meanings, V is a lower alkyl radical, and in the obtained compound of general formula IV, where R are the values of ester groups with a weak acid, and the obtained compound of general formula 1, where Y = C. = 0, is isolated in in free form or in the form of a salt, or to obtain compounds of the general formula 1, where Y is —C— or / H 1 Ί n he
    -C-, process complex /%
    BUT with an alkali metal hydride, such as sodium borohydride, after which the resulting products are isolated in the form of optically active · isomers or their racemates or in the form of their salts.
    Sources of information taken into account during the examination
    1. C.J. Sih et.al. Asymmetric ί Total Synthesis of (-) Prostaglandin E ^ and (-) Chem. Soc.
    Prostaqlandin · E „. J.Am.
    1975, p. 97,865. ^
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    US3987085A|1976-10-19|8β,11β,12α-PGF2.sub.α compounds
    US4060691A|1977-11-29|7-{3-Hydroxy-2-[4-hydroxy-4-|-trans-1-octen-1-yl]-5-oxocyclopent-1-yl}heptanoic acids and esters
    US4058564A|1977-11-15|Aliphatic 2-decarboxy-2-hydroxymethyl-13,14-didehydro-PG compounds
    US4202988A|1980-05-13|Prostenoic acids and esters
    KR20010014811A|2001-02-26|Process for preparing anti-osteoporotic agents
    HU193032B|1987-08-28|Process for preparing bicylic ketones
    US4293704A|1981-10-06|Novel 2-substituted-3,4-epoxycyclopentan-1-ones, 2-substituted-3,4-epoxycyclopentan-1-ols, and various 2-substituted-cyclopentenones
    US4237316A|1980-12-02|Novel 2-substituted-3,4-epoxycyclopentan-1-ones, 2-substituted-3,4-epoxycyclopentan-1-ols, and various 2-substituted-cyclopentenones
    US4086258A|1978-04-25|13,14-Didehydro-PGA1 compounds
    US4245121A|1981-01-13|Prostenoic acids and esters
    US4425359A|1984-01-10|Fluoro-prostaglandins and process for their preparation
    US4390711A|1983-06-28|16-Hydroxy-5-iodo-prostacyclin analogs of the 1 series
    US4235779A|1980-11-25|Bicyclic lactones
    US3897483A|1975-07-29|Novel 1-acyloxy-2-|cycloalk-1-enes
    US4190596A|1980-02-26|Various 15-deoxy-16-hydroxy-16-ethynyl and 16-ethynylsubstituted prostaglandins
    US4018803A|1977-04-19|13,14-Didehydro-PG3 compounds
    同族专利:
    公开号 | 公开日
    SE436741B|1985-01-21|
    CH636606A5|1983-06-15|
    BE856949A|1978-01-19|
    HU181840B|1983-11-28|
    ES460873A1|1978-10-01|
    AU512223B2|1980-10-02|
    FR2359127B1|1983-12-02|
    DE2731868A1|1978-02-02|
    PL121307B1|1982-04-30|
    DK324777A|1978-01-20|
    AU2658777A|1979-01-04|
    FR2359127A1|1978-02-17|
    NL7708020A|1978-01-23|
    CA1173826A|1984-09-04|
    DE2731868C2|1987-06-04|
    SE7708348L|1978-01-20|
    US4061670A|1977-12-06|
    GB1571641A|1980-07-16|
    US4131737A|1978-12-26|
    引用文献:
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    US05/706,343|US4061670A|1976-07-19|1976-07-19|15-Deoxy-16-hydroxy-16-vinyl and cyclopropyl substituted prostanoic acids and congeners|
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