Asymmetric Total Synthesis of Cephanolide A

Hongyuan Zhang; Haibing He; Shuanhu Gao

doi:10.1002/anie.202009562

Asymmetric Total Synthesis of Cephanolide A

Angew Chem Int Ed Engl. 2020 Nov 9;59(46):20417-20422. doi: 10.1002/anie.202009562. Epub 2020 Sep 15.

Authors

Hongyuan Zhang¹, Haibing He², Shuanhu Gao^{1

2}

Affiliations

¹ Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062, China.
² Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062, China.

PMID: 32749749
DOI: 10.1002/anie.202009562

Abstract

The first asymmetric total synthesis of cephanolide A, a complex hexacyclic C₁₈ dinorditerpenoid from cephalotaxus sinensis, was achieved. The synthesis features a convergent strategy, which provides a flexible approach to prepare the biogenetically cephalotaxus diterpenoids and structurally related derivatives for biological studies. A mild intramolecular Prins cyclization was developed to construct the central hexahydrofluorenol skeleton (A-B-C ring), which relies on the originally proposed hydroacylation strategy. A remote hydroxy group directed hydrogenation was applied to stereospecifically reduce the tetra-substituted enone unit. A sequence of ring forming steps, including lactonization, cation mediated etherification and Friedel-Crafts cyclization, was efficiently utilized to forge the cage-like skeleton.

Keywords: Prins cyclization; cephanolide A; diterpenoids; total synthesis.