PROCESS FOR THE PREPARATION OF DISCODERMOLIDE AND ITS ANALOGS.

摘要

A process for preparing a compound of formula V which comprises, in a first step, the coupling of a ketone compound of formula I With an aldehyde compound of formula II in the presence of a dialkyl boron hydride or triftalate, an amine base, and a polar organic solvent to obtain a -hydroxyketone of formula III In a second step, reducing the ketone compound obtained in the first step by treating with the borohydride reagent in a polar organic solvent and a protonic solvent to obtain a 1,3-diol of formula IV And, in a third step, the lactonization and deprotection of the acid labile hydroxyl protecting groups of the 1,3 diol obtained in the second step by treatment with hydrogen halide dissolved in a polar solvent or solvent mixture to obtain the desired compound of formula V, wherein R 1 is (C 1-6) alkyl, benzyl or an acid labile hydroxyl protecting group; R2 is (C1-6) alkyl or benzyl; R3 is hydrogen, (C1-6) alkyl, benzyl, C (O) (C1-12) alkyl, C (O) Ph, C (O) O (C1-12) alkyl, C (O) OPh, C ( O) NH (C1-12) alkyl, C (O) NHPh or an acid labile hydroxyl protecting group; R3 "is an acid-labile hydroxyl protecting group; R4 is hydrogen or methyl; and X is O, NH, NCH3, S or CH2, with the proviso that X is O and R3 is an acid-labile hydroxyl protecting group In the compound of formula I, the intermediate "-X-R3" in the compound of formula V is OH.