Synthesis and Stereochemical Revision of the C31–C67 Fragment of Amphidinol 3

• Published in: Angewandte Chemie International Edition 2018-05, Vol.57 (21), p.6060-6064
• Main Authors: Wakamiya, Yuma, Ebine, Makoto, Murayama, Mariko, Omizu, Hiroyuki, Matsumori, Nobuaki, Murata, Michio, Oishi, Tohru
• Format: Article
• Language: English
• Subjects: Absolute configuration; Alkenes - chemical synthesis; Alkenes - chemistry; Biological Products - chemical synthesis; Biological Products - chemistry; Carbon; Chains; Chemical synthesis; Configurations; Congeners; Degradation; Magnetic Resonance Spectroscopy; Molecular Conformation; Natural products; NMR; NMR spectroscopy; Nuclear magnetic resonance; Pyrans - chemical synthesis; Pyrans - chemistry; stereochemistry; Stereoisomerism; structure elucidation
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201712167

Amphidinol 3 (AM3) is a marine natural product produced by the dinoflagellate Amphidinium klebsii. Although the absolute configuration of AM3 was determined in 1999 by extensive NMR analysis and degradation of the natural product, it was a daunting task because of the presence of numerous stereogenic centers on the acyclic carbon chain and the limited availability from natural sources. Thereafter, revisions of the absolute configurations at C2 and C51 were reported in 2008 and 2013, respectively. Reported herein is the revised absolute configuration of AM3: 32S, 33R, 34S, 35S, 36S, and 38S based on the chemical synthesis of partial structures corresponding to the C31–C67 fragment of AM3 in combination with degradation of the natural product. The revised structure is unique in that both antipodal tetrahydropyran counterparts exist on a single carbon chain. The structural revision of AM3 may affect proposed structures of congeners related to the amphidinols. Under revision: Amphidinol 3 (AM3) is a marine natural product produced by the dinoflagellate Amphidinium klebsii. Although the absolute configuration of AM3 was determined in 1999 by extensive NMR analysis and degradation of the natural product, revisions of the absolute configurations at C2 and C51 were reported in 2008 and 2013, respectively. Reported herein is the revised absolute configuration of AM3: 32S, 33R, 34S, 35S, 36S, and 38S.