Synthetic Studies ond-Biotin, Part 8:[1] An Efficient Chemoenzymatic Approach to the Asymmetric Total Synthesis ofd-Biotinvia a Polymer-Supported PLE-Mediated Desymmetrization ofmeso-Symmetic Dicarboxylic Esters

A practical chemoenzymatic method for the asymmetric total synthesis of d-biotin (1) starting from the commercially available cis-1,3-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.