Synthetic Studies on d-Biotin,Part 8:An Efficient Chemoenzymatic Approach to the Asymmetric Total Synthesis of d-Biotin via a Polymer-Supported PLE-Mediated Desymmetrization of meso-Symmetic Dicarboxylic Esters

摘要

A practical chemoenzymatic method for the asymmetric total synthesis of d-biotin(1)starting from the commercially available cis-l,3-dibenzyl-2-imidazolidone-4,5-dicarboxylic acid(2)has been developed.The key step of the synthesis is the highly enantioselective hydrolysis of meso-dicarboxylic esters by a polymer-supported pig liver esterase and introduction of a formyl group at the C-4 position in 4 via a Grignard reaction.The polymer-supported PLE can be recovered quantitatively from the reaction mixture by simple filtration and reused without significant loss of activity.