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Asymmetric Total Synthesis of Cephanolide A
Author(s) -
Zhang Hongyuan,
He Haibing,
Gao Shuanhu
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202009562
Subject(s) - total synthesis , chemistry , intramolecular force , ring (chemistry) , stereochemistry , hydroacylation , prins reaction , enone , organic chemistry , catalysis , rhodium
The first asymmetric total synthesis of cephanolide A, a complex hexacyclic C 18 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.