Correlation of the absolute conformation of sec alcohols derived from macrocyclic lactones of resorcylic acid and their stereoselective transacetylation in organic solvents by Pseudomonas fluorescens lipase

Article abstract of DOI:10.1016/S0040-4020(01)85687-8

Transacetylation of diastereomeric pairs of sec. alcohols, derived from macrocyclic lactones of resorcylic acid; 7α,β-trans-zearalenols (1,2, full names; (3S,7R and 3S,7S) trans-3,4,5,6,9,10-octahydro-7,14,16-trihydroxy-3-methyl-1H-2-benzoxac yclotetradecine-1-ones), 7α,β-cis-zearalenols (5,6), and 7α,β-zearanols (9,10, full names; (3S,7R and 3S,7S)3,4,5,6,9,10,11,12-decahydro-7,14,16-trihydroxy-3-methyl-1H-2-be nzoxacyclotetradecine-1-ones) by vinylacetate, catalyzed by Pseudomonas sp. and Pseudomonas fluorescens lipase in n-heptane and acetonitrile has been studied. It is highly stereoselective; diastereomeric excess of 7β-O-acetates was usually near 100%. K(M), V(max) and specificity constant V(max)/K(M) do not significantly differ for 7β-stereoisomers 2, 6 and 10. However, they notably change on going from n-heptane to acetonitrile, and the specificity constant drops by factor ca 10-100. The enzyme-bound water is assumed to be partly released in the latter solvent, thus diminishing the interaction with the hydrophilic region of the substrates, and affecting the activity, but not the stereoselectivity of lipases. To correlate the structural and conformational properties of these substrates with unexpectedly high diastereoselectivity of enzymatic transacetylation, the solid state structures of 7β-isomers 2, 4, 6, 10 and 12 have been determined by X-ray analysis. The X-ray structure analysis has revealed that the 7α and 7β isomers possess notably different and in some cases almost mirror-image related absolute conformations around the reactive center. The importance of conformational chirality in the hydrophobic region of these substrates for stereoselection in transacylation by microbial lipases is discussed.