Total Synthesis of Keramaphidin B and Ingenamine by Base-Catalyzed Diels-Alder Reaction Using Dynamic Regioselective Crystallization

Yuki Kurihara; Minori Yagi; Takashi Noguchi; Haruka Yasufuku; Ayane Okita; Sho Yoshimura; Takeshi Oishi; Noritaka Chida; Toshitaka Okamura; Takaaki Sato

doi:10.1021/jacs.4c02338

Total Synthesis of Keramaphidin B and Ingenamine by Base-Catalyzed Diels-Alder Reaction Using Dynamic Regioselective Crystallization

J Am Chem Soc. 2024 Apr 9. doi: 10.1021/jacs.4c02338. Online ahead of print.

Authors

Affiliations

¹ Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.
² School of Medicine, Keio University, 4-1-1, Hiyoshi, Kohoku-ku, Yokohama 223-8521, Japan.

PMID: 38592076
DOI: 10.1021/jacs.4c02338

Abstract

The control of the selectivity is a central issue in the total synthesis of complex natural products. In this paper, we report the total synthesis of (±)-keramaphidin B and (±)-ingenamine. The key reaction is a DMAP-catalyzed Diels-Alder reaction in which the regioselectivity is completely controlled by dynamic crystallization. Our synthesis successfully demonstrates that dynamic crystallization can be an alternative when the selectivity is not controlled by either kinetic or thermodynamic approaches in solution.