Kinetic resolution of substituted 1,3-4 H-5,6-dihydrooxazines with carboxylesterase NP: Synthesis of (3 S,1t́ R)-3-(1′-hydroxyethyl)-azetidin-2-one

Abstract

The kinetic resolution of oxazinyl-ethyl carboxylates 4, is reported employing carboxylesterase NP as biocatalyst. Starting from the anti racemic stereoisomers 4c-d, the unreacted ester is obtained in 40 % yield and 93 % e.e. The enantiomeric acid is obtained in the open form. Cyclization of the latter and base equilibration allows recycling of the undesired stereoisomer. Compound 4d has the absolute configuration required in the azetidinone 3d, an intermediate in the synthesis of penems and carbapenems.