What question did this study set out to answer?

The aim is to develop an efficient and stereoselective total synthesis of glabridin, a valuable natural product.

May 17, 2026The Journal of Organic Chemistry0 citations

Asymmetric Total Synthesis of Glabridin

LXLong XuHebei University of Technology YGYuanqiang GuoTaiho Pharmaceutical (Japan)YZYuan ZhangTaiho Pharmaceutical (Japan)

Key Points

The aim is to develop an efficient and stereoselective total synthesis of glabridin, a valuable natural product.
Developed a six-step synthesis pathway for glabridin with key transformations.
Used a Mitsunobu reaction for fragment coupling and several mild transformations for assembly.
Achieved a final product with high enantiomeric excess (99.9% ee) and 19% overall yield.
Synthesis completed in six steps with 99.9% enantiomeric excess (ee).
Overall yield of glabridin was 19%.
Featured mild conditions and excellent selectivity during the synthesis process.

Abstract

Glabridin, a biologically important prenylated isoflavone, remains a persistent challenge for its efficient and stereoselective synthesis. We herein describe a novel asymmetric total synthesis of this natural product. The route commenced with the independent preparation of A-ring precursor a and B/C-ring fragment b. Glabridin was subsequently obtained in 99.9% ee over a concise six-step sequence, achieving an overall yield of 19%. The synthesis features several pivotal transformations: a Mitsunobu reaction to couple the key fragments; a hydroxy-iodination followed by a one-pot, intramolecular Friedel–Crafts alkylation and oxidation to efficiently assemble the tetracyclic core; and a final mild demethylation catalyzed by tris(pentafluorophenyl)borane. This route proceeds under mild conditions with excellent selectivity, offering a practical strategy for accessing Glabridin.

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