METHOD FOR PREPARING DISCODERMOLID AND ITS ANALOGS AND INTERMEDIATE COMPOUNDS Russian patent published in 2006 - IPC C07D309/30 C07C271/22 A61K31/365 A61P35/00 

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of discodermolid and its analogs of the formula (V): At the first step method involves the coupling reaction of ketone compound of the formula (I): with aldehyde compound of the formula (II): in the presence of dialkylboron halide or triphlate, amine base and polar organic solvent to yield β-hydroxyketone of the formula (III): at the second step method involves reduction of ketone compound synthesized at the first step by its treatment with boron hydride reagent in polar organic solvent medium and proton solvent to yield 1,3-diol of the formula (IV): at the third step method involves lactonization and removal of free acid-labile hydroxyl protective group of 1,3-diol synthesized at the second step by its treatment with hydrogen halide dissolved in polar solvent or mixture of solvents to yield the end compound of the formula (V) wherein R₁ means (C₁-C₆)-alkyl; R₂ means (C₁-C₆)-alkyl; R₃ means hydrogen atom or acid-labile hydroxyl protective group; R₃'' means acid-labile hydroxyl protective group; R₄ means hydrogen atom or methyl group; X means oxygen atom (O) under condition that when X means O and R₃ means acid-labile hydroxyl protective group of compound of the formula (I) then residue -X-R₃ in compound of the formula (V) represents hydroxyl group (-OH). Also, invention relates to novel intermediate compounds of formulae (I), (III) and (IV) and to a method for synthesis of compound of the formula (I). Invention provides a new method for synthesis of the valuable compound discodermolid and its analogs with the satisfied yields.

EFFECT: improved method of synthesis.

16 cl, 4 ex