Total Synthesis of (+)-Gracilamine Based on an Oxidative Phenolic Coupling Reaction and Determination of Its Absolute Configuration

Minami Odagi; Yoshiharu Yamamoto; Kazuo Nagasawa

doi:10.1002/anie.201708575

Total Synthesis of (+)-Gracilamine Based on an Oxidative Phenolic Coupling Reaction and Determination of Its Absolute Configuration

Angew Chem Int Ed Engl. 2018 Feb 19;57(8):2229-2232. doi: 10.1002/anie.201708575. Epub 2017 Oct 11.

Authors

Minami Odagi¹, Yoshiharu Yamamoto¹, Kazuo Nagasawa¹

Affiliation

¹ Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, TUAT, 2-24-16, Naka-cho, Koganei city, 184-8588, Tokyo, Japan.

PMID: 28929558
DOI: 10.1002/anie.201708575

Abstract

The enantioselective total synthesis of (+)-gracilamine (1) is described. The strategy features a diastereoselective phenolic coupling reaction followed by a regioselective intramolecular aza-Michael reaction to construct the ABCE ring system. The configuration at C3a in 1 was controlled by the stereocenter at C9a, which was selectively generated (91 % ee) by an organocatalytic enantioselective aza-Friedel-Crafts reaction developed by our research group. This synthesis revealed that the absolute configuration of (+)-gracilamine is 3aR, 4S, 5S, 6R, 7aS, 8R, 9aS.

Keywords: aza-Friedel-Crafts reaction; natural products; organocatalysis; oxidative phenolic coupling; total synthesis.

Publication types

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