Improved Synthesis of C4α- and C4β-Methyl Analogues of 2-Aminobicyclo[3.1.0]hexane-2,6-dicarboxylate

An efficient and divergent synthesis of C4α- and C4β-methyl-substituted analogues of 2-aminobicyclo[3.1.0]hexane 2,6-dicarboxylate, which are important tools in the study of metabotropic glutamate receptor function, has been achieved. By taking advantage of an unanticipated facial selectivity of the bicyclo[3.1.0]hexane ring system, either the C4α- or C4β-methyl substituent was introduced in a highly stereoselective and high-yielding manner

Development of an Enantioselective Hydrogenation Based Synthesis of a Glucokinase Activator

This article describes the development and optimization of chemical reactions and subsequent multikilogram preparation of the glucokinase activator (<i>R</i>)-<b>1</b> to fund clinical evaluation as a potential therapeutic for type II diabetes. The major process developments presented here are a Wittig olefination isomerization based synthesis of an <i>E</i>-acrylic acid, an optimized enantioselective hydrogenation of the <i>E</i>-acrylic acid, and a challenging final amide coupling