Process for preparing leurozine-type alkaloids or their acid addition salts

专利摘要:
A process for the preparation of alkaloids of the leurosine type having the formula I <IMAGE> (I) and the acid addition salts thereof. In the formula I R is hydrogen or methyl. The compounds prepared according to the invention are known compounds showing cytostatic activity.
公开号:SU1055333A3
申请号:SU792753361
申请日:1979-04-23
公开日:1983-11-15
发明作者:Сантаи Чаба；Сабо Лайош；Хонти Каталин；Ногради Каталин；Яванович Карой
申请人:Рихтер Гедеон Ведьесети Дьяр Рт (Инопредприятие)；
IPC主号:

专利说明:

can be used as a starting material, the eluate obtained from the layer with acetone, which has a reduced reactivity, is dried and the residue is triturated with ether; 0.7 g of H-desmethyl-N-formylvindoline (ZkfQ%) j is obtained; the product, christated from ether, is melted by Example 2. H-Desmethyl8indoline g (1.19 mmol) of N-desmethyl-N-formylvinroline is dissolved under nitrogen atmosphere at 110 ml of methanolic hydrochloric acid. The solution is maintained for 3 hours with a methanol 10% ammonium solution which is then adjusted to pH 7. The neutralized solution is evaporated at a low pressure to a volume of 20 ml, and 30 ml of ice water is added to the residue, and then with diluted aqueous ammonium hydroxide solution (1: 1) set the pH value of 9. The alkaline solution obtained is extracted three times with 20 MJ. dichloromethane (each time 20 ml), the organic extracts purified, dried with magnesium sulfate, filtered and the filtrate is evaporated under reduced pressure. The residue is crystallized from 10 ml of ether, to obtain 00 mg of N-desmethylvindoline (78.7). Mp. P8 ° C (ether). EXAMPLE Desmethyl Vindolin The treatment is carried out as in Example 2 with the only difference that the hydrolysis is carried out in the presence of aqueous 2% sulfuric acid instead of hydrochloric, with an M-desmethyl-Vindoline yield of 79.1% Example „N-Desmethyl-I-anhydrideinblastin. mg (1.01 mmol j catarantina dissolved in 17 ml of anhydrous dichloromethane. The solution is cooled and 15 mg of perpelargonic acid (1.1 eq) in 3 mg) are added to the solution with stirring in a nitrogen atmosphere for 15 min. ml of dichloromethane. The mixture is cooled to, mixed with Af2 mg (1.0 mmol) of N-desmethylvindoline with 0.82 ml (3.8 mmol) of freshly distilled trifluoroacetic anhydride. The mixture of reagents is maintained for 18 hours at a temperature between -10 and then To the mixture is added a solution of l4o mg sodium borohydride in ml anhydrous methanol at -10 ° C. (layered chromatography (adsorbent: silica gel: solvent: mixture of dichloromethane and methanol, respectively, 20: 2). At the end of the reaction, the mixture is concentrated to a quarter of the volume with a. The residue is washed with 15 vn dichloromethane and then using a 1: 1 diluted aqueous solution ammonium hydroxide solution is adjusted to pH 3; the phases are separated, the organic phase is extracted twice with 10 ml of water, the aqueous phase is collected and extracted twice with 10 ml of dichloromethane, the dichloromethane phases are dried with magnesium sulfate and filtered and the filtrate is evaporated under reduced pressure. The evaporated residue is purified by layer chromatography (adsorbent, solvent, and eluent as in Example 1). The eluate obtained from acetone and containing the product is evaporated and the residue is recrystallized from methanol, to obtain 315 mg of M-desmethyl-3 aigidrovinblastin (0.2 from the theory); t, pl. 202-20 4; , (with 1.06 in chloroform). Instead of using N-desmethyl-vindolin using an equivalent amount of vindole yield 3, anhydrous inorganic acid is state et a, T. -215-21 ° C; No. ° + 71 ° C (s in chloroform),. Example 5oN-Desmethyl-, anhydrovinblastin sulfate 0.1 g of I-desmetip-3 j anhydrovinblastin are suspended in 1 ml of anhydrous methanol, then methanolic sulfuric acid is added until pH 5 is reached. After the addition of 3 ml of ether, an acid addition salt is formed. The resulting crystals are filtered and dried, the N-desmethyl-3, anhydride-inoblast sulfate is melted at, The yield is 95 from the theory. An example of boM-Desmethyl-M-formyllerosin, 100 mg (0.012C, resin, N-desmethyl-N-formyl-3, anhydrin -inblast, dissolved in 3 ml of benzene, then / mg 2,2-azobis-isobutyronitrile is added to the solution. Mixture cooled to, then a solution of 160 mg (o, 75 mmol) of 70% cumyl hydroperoxide in 1 ml of benzonitrile is added with stirring under nitrogen atmosphere. The mixture of reagents is kept in a stream of nitrogen at C, 5 ml of benzene are added and then

权利要求:
Claims (1)
[1]
The method of producing alkaloids such as leurosin of General formula I
Where R is hydrogen or formyl, or their acid addition salts, including formylation of N-desmethyllerosine with formic acid in acetic anhydride and isolation of the target product in free form or in the form of an acid addition salt, which is characterized in that, in order to simplify the process compounds of General formula And
OSOSnz
COOCHs are reacted with quarantine N-oxide and then with sodium borohydride and the resulting compound of general formula
O) c, in the presence of an acid and a solvent containing a nitrile group and, if necessary, 2,2-azobisisobutyronitrile, epoxidized with tert-butyl or cumyl hydroperoxide, followed by the formation of N-desm, tillerosin, if necessary.
>
1 1055333

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FR2296418B1|1974-12-30|1978-07-21|Anvar|

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US4279817A|1975-05-30|1981-07-21|The United States Of America As Represented By The Department Of Health & Human Services|Method for producing dimer alkaloids|

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法律状态:

优先权:

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申请号 | 申请日 | 专利标题

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HU77RI632A|HU180924B|1977-05-20|1977-05-20|Process for producing leurosine-type alkaloides|

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