Biocatalytic Access to Chiral Polyesters by an Artificial Enzyme Cascade Synthesis

Chiral polyesters in general can be employed for versatile biomedical purposes, but in vitro enzyme catalyzed biocatalytic routes by a multiple‐step cascade to make these functional biodegradable chiral polyesters have been hardly investigated. Recently, we developed an artificial three‐step enzymatic cascade synthesis by combining an alcohol dehydrogenase (ADH), a Baeyer–Villiger monooxygenase (BVMO) and a lipase (CAL‐A). Here, we extended this cascade for the synthesis of chiral methyl‐substituted oligo‐ɛ‐caprolactone derivatives to achieve both, the generation of chirality in a monomer and the subsequent polymerization. Several substrates were examined and provided access to functionalized chiral compounds in high yields (up to >99 %) and optical purities (up to >99 % ee). By subsequent enzymatic enantioselective ring opening of the enantiopure monomers, oligomeric lactones were successfully synthesized. Rotate me! By combining three enzymes (LK‐ADH, CHMO, CAL‐A), which are evolutionary not connected, to an artificial cascade, optically active chiral oligomers can be synthesized from nonchiral or racemic methyl‐substituted cyclohexanol derivatives.