A GENERAL CHEMOENZYMATIC SYNTHESIS OF ENANTIOPURE CIS BETA-AMINO ALCOHOLS FROM MICROBIALLY DERIVED CIS-GLYCOLS

Enantiomerically pure cis-glycols, derived through the microbial metab olism of hydrocarbons, represent a valuable chiral pool for the synthe sis of cis beta-amino alcohols. One generally applicable route to thes e important chiral intermediates is described. Reaction of the metabol ically formed diol with alpha-acetoxy-isobutyryl chloride affords regi o- and stereoselectively a single trans-1,2-chlorohydrin acetate isome r. Displacement of chloride by azide, aminolysis of the ester and redu ction of the azide provides the requisite amino alcohols. This 4-step route is highly efficient and affords the cis beta-amino alcohol enant iomers in 41-57% overall yields. Using the highly enantiopure amino al cohols diastereomeric oxazaborolidines were prepared with both (-)-(S) - and (+)-(R)-[2-(1-methoxyethyl)phenyl]boronic acids. As described he rein, these derivatives are potentially useful for absolute configurat ional assignments to cis amino alcohols.