Enantioselective Synthesis of (-)-10-Hydroxyacutuminine

Denise C Grünenfelder; Raul Navarro; Haoxuan Wang; Nicholas J Fastuca; John R Butler; Sarah E Reisman

doi:10.1002/anie.202117480

Enantioselective Synthesis of (-)-10-Hydroxyacutuminine

Angew Chem Int Ed Engl. 2022 Apr 11;61(16):e202117480. doi: 10.1002/anie.202117480. Epub 2022 Feb 23.

Authors

Denise C Grünenfelder¹, Raul Navarro¹, Haoxuan Wang¹, Nicholas J Fastuca¹, John R Butler¹, Sarah E Reisman¹

Affiliation

¹ The Warren and Katharine Schlinger Laboratory of Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.

PMID: 35112449
DOI: 10.1002/anie.202117480

Abstract

An enantioselective synthesis of (-)-10-hydroxyacutuminine is reported. Central to our strategy is a photochemical [2+2] cycloaddition that forges two of the quaternary stereocenters present in the acutumine alkaloids. A subsequent retro-aldol/Dieckmann sequence furnishes the spirocyclic cyclopentenone. Efforts to chlorinate the acutumine scaffold at C10 under heterolytic or radical deoxychlorination conditions led to the synthesis of an unexpected cyclopropane-containing pentacycle.

Keywords: Acutumine Alkaloids; Deoxychlorination; Dieckmann Cyclization; Total Synthesis; [2+2] Cycloaddition.

Publication types

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

MeSH terms

Cyclization*
Cycloaddition Reaction
Stereoisomerism