Enzymatic kinetic resolution of hydroxystearic acids: A combined experimental and molecular modelling investigation

Enantioenriched 7-, 8-, 9-, and 10-hydroxystearic acids (HSA) were obtained, for the first time, by kinetic resolution of their racemates with lipases CALB and PS, in the presence of vinyl acetate. Among them, the best results were obtained for 7-HSA and 9-HSA, whose enantiomeric excess was around 55%. The same resolutions carried out on the hydroxy esters completely failed. For the acid substrates neither the Kazlauskas’ rule nor the 3D-QSAR model could be applied, since both models are focused on the CALB alcohol-pocket evaluation and not on the acyl-pocket one. Therefore, a semiquantitative approach was used, whose results were in accordance with our findings, as far as the absolute configuration of the product is concerned.

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► Enantioenriched hydroxystearic acids were obtained by enzymatic kinetic resolution.
► Lipases CALB and PS in the presence of vinyl acetate were used.
► Acyl moiety can be docked in hydroxyl-pocket only upon conformational modification.
► Catalysis occurs despite unfavored placement of acyl group in hydroxyl-pocket.
► These hydroxy-fatty acids are recognized by lipase as acids rather than alcohols.