Modular Stereodivergent Chemoenzymatic Total Synthesis of (+)‐ and (‐)‐ <i>Glabridin</i>
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.
Authors
- Yin Wei
- Min Shi
- Min Li
- Xuan Wang
- Renhao Shi
Institutions
- Shanghai Institute of Organic Chemistry (CN)
Publication Details
- Journal
- Chemistry - A European Journal
- Published
- 2026-03-26
- DOI
- https://doi.org/10.1002/chem.70931
- Primary Topic
- Pharmacological Effects of Natural Compounds
- Type
- article
- Field-Weighted Citation Impact
- 0.00