| 摘要 |
FIELD: chemical technology. ^ SUBSTANCE: invention relates to variants of a method for synthesis of a mixture (E)- and (Z)-isomers of ISATX247. By one variant acetyl-ciclosporin is heated with the first compound chosen from group consisting of triarylphosphine, trialkylphosphine, arylalkylphosphine and triarylarsine for preparing an intermediate substance that is stirred with the second compound chosen from group consisting of acetaldehyde, formaldehyde, deuterium-labeled formaldehyde, 2-chlorobenaldehyde and benzaldehyde. Mixture of (E)- and (Z)-isomers of acetyl-1,3-diene is prepared that is treated with a base and mixture of (E)- and (Z)-isomers of ISATX247 is prepared. Other variant for preparing mixture of (E)- and (Z)-isomers of ISATX247 represents interaction of acetyl-ciclosporin A aldehyde that is prepared by oxidation of acetyl-ciclosporin A, with phospholide by Wittig reaction followed by treatment of the prepared mixture with a base. Also, invention relates to a method for synthesis of mixture of (E)- and (Z)-isomers of ISATX247 enriched with E-isomers or Z-isomer, and to a method for synthesis of the preliminary assigned isomeric mixture of (E)- and (Z)-isomers of ISATX247 by mixing materials enriched with (E)- and (Z)-isomers. ^ EFFECT: improved method of synthesis. ^ 77 cl, 7 tbl, 16 dwg, 39 ex |
