Chemistry. 2026 Mar 26:e70931. doi: 10.1002/chem.70931. Online ahead of print.

ABSTRACT

Herein, we describe a modular, stereodivergent chemoenzymatic strategy for the enantioselective total synthesis of the natural products (+)- and (-)-glabridin. A lipase-catalyzed dynamic kinetic resolution establishes the key benzylic stereocenter, while a carefully engineered protecting-group manifold preserves stereochemical integrity during fragment coupling and cyclization. From inexpensive, commercially available resorcinol-derived building blocks, the sequences deliver (-)-glabridin in 10 steps with 14% overall yield and (+)-glabridin in 12 steps with 7% overall yield. This convergent platform provides practical access to both enantiomers of glabridin and offers a general blueprint for the stereocontrolled synthesis of structurally related polyphenolic natural products.

PMID:41888064 | DOI:10.1002/chem.70931