A strategic approach to [6,6]-bicyclic lactones: application towards the CD fragment of DHβE

Tue Heesgaard Jepsen; Emil Glibstrup; François Crestey; Anders A Jensen; Jesper Langgaard Kristensen

doi:10.3762/bjoc.13.98

A strategic approach to [6,6]-bicyclic lactones: application towards the CD fragment of DHβE

Beilstein J Org Chem. 2017 May 22:13:988-994. doi: 10.3762/bjoc.13.98. eCollection 2017.

Authors

Tue Heesgaard Jepsen^#¹, Emil Glibstrup^#¹, François Crestey¹, Anders A Jensen¹, Jesper Langgaard Kristensen¹

Affiliation

¹ Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.

^# Contributed equally.

Abstract

We report an effective synthetic protocol to access [6,6]-bicyclic lactone moieties through a regio- and stereoselective intramolecular Mizoroki-Heck cross-coupling reaction followed by a 6π-electrocyclization. This method enabled the first synthesis of the elusive CD fragment of the Erythrina alkaloid DHβE. Preliminary pharmacological evaluations support the notion that the key pharmacophores of DHβE are located in the A and B rings.

Keywords: 6π-electrocyclization; DhβE; Mizoroki–Heck cross-coupling reaction; [6,6]-bicyclic lactone; vinyl halide.