(6R,7S,8R)-7,8-di:azido-6,9-di:silyl-oxy-nonanoate ester prepn. - by silylation of A 6,7,8,9-tetra:hydroxy-nonanoic acid ester followed by reaction with a sulphonic acid chloride and sodium azide

摘要

The prepn. of (6R,7S,8R)-7,9-diazido-6,9-disilyloxy-nonanoic acid ester of formula (I) comprises: (a) reacting a (6R,7S,8R), 6,7,8,9-tetrahydroxy-nonanoic acid ester of formula (II) with tert. butyl-dimethylsilyl chloride or thexyldimethylsilyl chloride in an inert solvent in the presence of a base; (b) reacting the (6R,7S,8R)-6,9-disilyloxy-7,8-dihydroxy-nonanoic acid ester of formula (III) formed with a sulphonic acid chloride of formula R3SO2Cl (IV) in pyridine, and (c) reacting the resulting (6R,7S,8R)-6,9-disilyl-oxy-7,8-disulphonyloxy-nonanoic acid ester of formula (V) with sodium azide in dimethylsulphoxide at 100-130 (esp. 115-125)deg.C. In formulae, R1 = 1=4C alkyl, R2 = tert. butyldimethylsilyl or thexyldimethylsilyl, and R3 = Me or p-tolyl. USE/ADVANTAGE - (I) are intermediates in the prepn. of (+)-biotin (vitamin H) which, as a co-factor of enzymes, plays a decisive role in biochemical processes in which carbonic acid is transferred or fixed. The process uses fewer reaction steps to produce (I) than previously. Starting from D-arabinose, it is possible to prepare (I) in only 10 synthesis steps - the shortest so far.