Methods for the preparation of highly functionalized bicyclo[3.1.0]hexane mGluR2/3 agonists

Abstract

A few different approaches for the preparation of highly substituted bicyclo[3.1.0]hexane mGluR2/3 agonists are reviewed. Addition and elimination, carbene insertion, SN2 type cyclization, and application of Trost's asymmetric allylic alkylation (AAA) are methods of choice for the construction of the ring system. Functionalization of the bicyclo[3.1.0]hexane core structure and synthesis of one of the most potent and selective mGluR2/3 agonists, MGS0028, are also reviewed.