Total Synthesis of Zephycarinatines via Photocatalytic Reductive Radical ipso-Cyclization

Haruka Takeuchi; Shinsuke Inuki; Kohei Nakagawa; Takaaki Kawabe; Atsuhiko Ichimura; Shinya Oishi; Hiroaki Ohno

doi:10.1002/anie.202009399

Total Synthesis of Zephycarinatines via Photocatalytic Reductive Radical ipso-Cyclization

Angew Chem Int Ed Engl. 2020 Nov 16;59(47):21210-21215. doi: 10.1002/anie.202009399. Epub 2020 Sep 11.

Authors

Haruka Takeuchi¹, Shinsuke Inuki¹, Kohei Nakagawa¹, Takaaki Kawabe¹, Atsuhiko Ichimura¹, Shinya Oishi¹, Hiroaki Ohno¹

Affiliation

¹ Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan.

PMID: 32770565
DOI: 10.1002/anie.202009399

Abstract

We report herein a nonbiomimetic strategy for the total synthesis of the plicamine-type alkaloids zephycarinatines C and D. The key feature of the synthesis is a stereoselective reductive radical ipso-cyclization using visible-light-mediated photoredox catalysis. This cyclization enabled the construction of a 6,6-spirocyclic core structure through the addition of a carbon-centered radical onto the aromatic ring. Biological evaluation of zephycarinatines and their derivatives revealed that the synthetic derivative with a keto group displays moderate inhibitory activity against LPS-induced NO production. This approach could offer future opportunities to expand the chemical diversity of plicamine-type alkaloids as well as providing useful intermediates for their syntheses.

Keywords: alkaloids; natural products; photocatalysis; radical ipso-cyclization; total synthesis.

Publication types

Research Support, Non-U.S. Gov't