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Updated: Dec 9, 2025

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Unified Total Synthesis of (-)-Enigmazole A and (-)-15-O-Methylenigmazole A
Keisuke Sakurai1, Keita Sakamoto2,1, Makoto Sasaki1
1Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, 980-8577, Japan.
Abstract:
The total synthesis of cytotoxic marine phosphomacrolides, (-)-enigmazole A and (-)-15-O-methylenigmazole A, is described in detail. The 2,6-cis-substituted tetrahydropyran ring was efficiently elaborated by using a tandem olefin cross-metathesis/intramolecular oxa-Michael addition reaction. The 18-membered macrolactone skeleton was forged via a Au-catalyzed propargylic benzoate rearrangement/macrocyclic ring-closing metathesis sequence. Late-stage diversification of a common intermediate enabled unified total synthesis of (-)-enigmazole A and (-)-15-O-methylenigmazole A.
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