Unified Total Synthesis of (−)‐Enigmazole A and (−)‐15‐O‐Methylenigmazole A. Issue 21 (1st October 2020)

• Record Type: Journal Article
• Authors: Sakurai, Keisuke; Sakamoto, Keita; Sasaki, Makoto; Fuwa, Haruhiko
• Is Part Of: Chemistry, an Asian journal. Volume 15:Issue 21(2020)
• Page Start: 3494
• Page End: 3502
• Publication Date: 2020-10-01
• Subjects: macrocycles -- natural products -- tandem reaction -- gold-catalyzed reaction -- tetrahydropyrans; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/asia.202001015
• Languages: English
• ISSNs: 1861-4728

Abstract

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. Abstract : The total synthesis of (−)‐enigmazole A and its natural congener (−)‐15‐ O ‐methylenigmazole A has been achieved. The tetrahydropyran ring was constructed by using a tandem olefin cross‐metathesis/intramolecular oxa‐Michael addition. The 18‐membered macrolactone was formed via a Au‐catalyzed propargylic benzoate rearrangement/macrocyclic ring‐closing metathesis sequence.