Enzymes in organic synthesis 49. Resolutions of racemic monocyclic esters with pig liver esterase.

Abstract Pig liver esterase (PLE)- catalyzed hydrolyses of the racemic methyl esters of cyclobutane-, cyclohexane-, and cyclohex-4-ene-carboxylic acids bearing cis-2-methyl or cis-2-bromomethyl substituents are highly stereoselective, giving the corresponding acid products of ≥ 97% ee. The stereoselectivity of the enzyme exhibits the expected reversal for such compounds, with the absolute configurations of the cyclobutane and cyclohexane acids being of the opposite absolute configuration types, and cyclopentane substrates such as cis-1-carbomethoxy-2-methylcyclopentane representing the change-over structures and giving products of only 22%ee. This stereoselectivity reversal, and the absolute configurations preferred, are as predicted by the recently proposed active site model for the enzyme.