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Published on: June 13, 2022
Total Synthesis of (-)-Enigmazole A by the Macrocyclization/Transannular Pyran Cyclization Strategy: Application to
Kyoya Ohyama1, Taisei Masuda1, Keita Sakamoto1
1Department of Applied Chemistry, Faculty of Science and Engineering, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551, Japan.
None:
An 18-step total synthesis of (-)-enigmazole A was achieved by means of our macrocyclization/transannular pyran cyclization strategy. Specifically, the 18-membered macrolactone skeleton of (-)-enigmazole A was constructed from three readily available building blocks through a Horner-Wadsworth-Emmons olefination, a Yamaguchi esterification, a macrocyclic ring-closing metathesis, and a transannular oxa-Michael addition as key transformations. Furthermore, late-stage diversification of the 18-membered macrolactone skeleton enabled access to a series of synthetic analogues that were useful for investigating the structure-activity relationship of (-)-enigmazole A.
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