Modular Stereodivergent Chemoenzymatic Total Synthesis of (+)‐ and (‐)‐ Glabridin
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.
Fields of Study & Subjects
Pharmacological Effects of Natural Compounds
Chemical synthesis and alkaloids
Plant and fungal interactions
Publication details
- Journal / source
- Chemistry - A European Journal
- Publisher
- Wiley
- Volume
- 32
- Issue
- 22
- Pages
- e70931–e70931
- Publication date
- 26 March 2026
- Language
- EN