VITAMIN D PRECURSORS, METHOD FOR PREPARATION THEREOF, AND INTERMEDIATES Russian patent published in 2005 - IPC

FIELD: organic synthesis.

SUBSTANCE: invention relates to A-ring precursors of vitamin D having formula I:

in which A represents -CH₂OH, -CH₂-OCOR', -COR", or ethynyl; R represents hydrogen or C₁-C₆-alkyl; R₁ hydrogen, C₁-C₆-alkyl, or (CH₂)_nOP; R₂ hydrogen or -OP; R' is phenyl; R" hydrogen, hydroxyl, C₁-C₆-alkoxy; P hydrogen or group -Si(R₃)₃, wherein each R₃ independently represents C₁-C₆-alkyl or phenyl; n = 0 or 1, provided that, when compound I has configuration 2S,3aS,4aS, A is formyl, hydroxymethyl, ethynyl, or methoxycarbonyl, and R and R₂ are both hydrogen atoms, then R₁ is not -OSi(R₃)₃.Preparation of compounds I comprises: (i) interaction of compounds having general formula 1:

,

in which A represents C₁-C₆-alkoxycarbonyl or C₁-C₃-alkylaminocarbonyl, with lipase in vinyl alkanoate or acid anhydride and (ii) conversion of resulting compound of formula 2: (2) or 2': (2'), where Z represents alkyl, preferably C₁-C₃-alkyl, into corresponding compound I via formation of a leaving group and cyclization caused by treatment with a base to form desired bicyclo[3.1.0]hexane, said conversion comprising: protection of hydroxy groups, hydrolysis of ester, inversion of 3- or 5-hydroxy group, and converting carboalkoxy or carbamoyl group into desired substituent A.

EFFECT: optimized synthesis conditions allowing more effective larger-scale preparation of precursors.

8 cl, 4 dwg, 45 ex