A novel chemoenzymatic strategy for the synthesis of enantiomerically pure secondary alcohols with sterically similar substituents is described. The key step is the kinetic lipase-catalyzed resolution of racemic mixtures of substituted propargylic alcohols. The efficiency of this new approach was tested in the preparation of the corresponding enantiomers of 1,11-hexadecandiol derivatives ((R)-5 and (S)-5). Two strategies were tested. In the first one, the racemic intermediate 1-octyn-3-ol (1) was resolved enzymatically and then elongated with 1-bromo-9,11-dioxadodecane. Alternatively, the racemic 1 can be elongated to the corresponding racemic 17,19-dioxa-7-eicosyn-6-ol (3) first and then resolved biocatalytically. Twelve commercially available lipases were screened for the kinetic resolution of these intermediates. Among them, Candida antarctica lipase (CAL-B) and Humicola lanuginosa lipase (HLL) were the best biocatalysts for the resolution of 1 (S enantiomer 90% ee, E = 35), and 3 (R enantiomer 90% ee, E = 34), respectively.

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