Practical Methods for the Synthesis of Symmetrically α,α-Disubstituted α-Amino Acids

Abstract

This report provides an overview of the practical methods for preparing symmetrically α,α-disubstituted α-amino acids and their derivatives. Despite the growing application of this particular type of sterically constrained α-amino acid in the de novo design of peptides and peptidomimetics, synthetically important achievements in the field have not been summarized so far. Classical methods, such as the Bucherer-Bergs and Strecker reactions of sym-dialkyl and cyclic ketones, as well as recent methods involving dialkylation of nucleophilic glycine equivalents and Ugi reactions, are presented. 1 Introduction 2 Bucherer-Bergs and Strecker Reactions of sym-Dialkyl and Cyclic Ketones 3 Dialkylation of Schiff Bases Derived from Glycine Esters 4 Dialkylation of Ethyl Isocyanoacetate 5 Dialkylation of Ethyl Nitroacetate 6 Ugi Reaction 7 Conclusions