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Modular Stereodivergent Chemoenzymatic Total Synthesis of (+)- and (-)-Glabridin
Xuan Wang1, Min Li1, Renhao Shi1
1State Key Laboratory of Organometallic Chemistry, Center For Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
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.
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