Approaches to Construction of the Medium-Sized Ring Structure in Zetekitoxin AB by Ring-Closing Metathesis

Hayate Ishizuka; Ayato Nureki; Kanna Adachi; Yuka Takayanagi; Minami Odagi; Mari Yotsu-Yamashita; Kazuo Nagasawa

doi:10.1021/acs.joc.3c00580

Approaches to Construction of the Medium-Sized Ring Structure in Zetekitoxin AB by Ring-Closing Metathesis

J Org Chem. 2023 Jul 21;88(14):10223-10231. doi: 10.1021/acs.joc.3c00580. Epub 2023 Jun 28.

Authors

Hayate Ishizuka¹, Ayato Nureki¹, Kanna Adachi¹, Yuka Takayanagi¹, Minami Odagi¹, Mari Yotsu-Yamashita², Kazuo Nagasawa¹

Affiliations

¹ Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16, Naka-cho, Koganei, Tokyo 184-8588, Japan.
² Graduate School of Agriculture Science, Tohoku University, 468-1 Aramaki-Aza-Aoba, Aoba-ku, Sendai 980-8572, Japan.

PMID: 37378952
DOI: 10.1021/acs.joc.3c00580

Abstract

Zetekitoxin AB (ZTX), a member of the saxitoxin (STX) family isolated from the Panamanian golden frog Atelopus zeteki, shows extremely potent Na_V-inhibitory activity. Here, we investigate the synthesis of 12-membered ring structure with the C11 tertiary hydroxyl group in ZTX by means of the Mislow-Evans rearrangement reaction and subsequent ring-closing metathesis reaction. Although this approach did not provide access to the 12-membered macrocycle, we obtained a new STX analog with an 18-membered macrolactam structure as a synthetic mimic of ZTX.