Synthetic Studies on d‐Biotin, Part 8:[1] An Efficient Chemoenzymatic Approach to the Asymmetric Total Synthesis of d‐Biotin via a Polymer‐Supported PLE‐Mediated Desymmetrization of meso‐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.