Biotransformation in organic synthesis: applications of yeast reduction in the synthesis of 3,5-dihydroxy esters of high optical purity

Abstract

All four stereoisomers of methyl 6-(p-chlorophenylthio)-3,5-dihydroxyhexanoate have been synthesised by a route in which the key introduction of chirality was effected by an appropriate yeast reduction.Because polyoxygenated units occur in many polyether and biological conversion of a (3-keto ester into a (3-hydroxy ester macrolide antibiotics' their synthesis has attracted much followed by chain extension to generate a 3-oxo-5-hydroxy attention. We have investigated an approach which would ester. Reduction of the chain-extended system could then be provide an iterative route to such systems. As outlined in effected either by chemical procedures or by a further Scheme 1, this was envisaged as beginning with stereospecific biotransformation. We have found that such a sequence,

Baker's‐Yeast‐Mediated Reduction of Sulfur‐Containing Compounds

“…Interestingly, on introduction of a sulfur moiety into the γ‐position of the β‐keto ester, the absolute configuration of the resulting β‐hydroxy ester was inverted from S to R . This anti‐Prelog enantiopreference was observed in the enantioselective baker's‐yeast‐mediated reduction of β‐keto γ‐phenyl thioester 10a 64 and γ‐phenyl sulfonyl ester derivative 10b (Scheme ) 25. The latter was reduced with greater enantioselectivity (98 % ee vs. 73 % ee ), and subsequent sulfur group cleavage yielded the ( R )‐β‐hydroxy ester 11 .…”