Enzymatic resolution of a chiral chlorohydrin precursor for (R)-α-lipoic acid synthesis via lipase catalyzed enantioselective transacylation with vinyl acetate

•A novel process was developed to produce a key precursor for (R)-α-lipoic acid.•Increase E value by designing the reacted site (OH group) on the chiral center.•Redesigned and optimized the producing process.•Succeeded in repetitive use of catalyst for producing the target products.

A new and efficient process was developed by lipase-catalyzed transacylation to resolve ethyl 8-chloro-6-hydroxy octanoate (ECHO) to produce an important chiral precursor for the synthesis of (R)-α-lipoic acid. After optimization of biocatalyst, solvent, acyl donor, temperature and enzyme loading, (S)-O-acetylated ECHO was achieved in 94% ee, 35% isolated yield and 38 g L−1 d−1 space-time yield using Novozym 435 as biocatalyst. Subsequently, the enzymatic resolution reaction was successfully repeated for 7 batches, retaining over 40% conversions.

Graphical abstractA new and efficient process was developed by lipase-catalyzed transacylation to resolve ethyl 8-chloro-6-hydroxy octanoate (ECHO) to produce an important chiral precursor for the synthesis of (R)-α-lipoic acid.Figure optionsDownload full-size imageDownload as PowerPoint slide