Tailor-Made α-Amino Acids in the Pharmaceutical Industry: Synthetic Approaches to (1R,2S)-1-Amino-2-vinylcyclopropane-1-carboxylic Acid (Vinyl-ACCA)

(1R,2S)-1-Amino-2-vinylcyclopropane-1-carboxylic acid (vinyl-ACCA) is the essential pharmacophoric unit in a new generation of highly potent hepatitis C virus (HCV) NS3/4A protease inhibitors. Currently, there are over a dozen drugs under development that use the special properties of this highly sterically constrained tailor-made amino acid, underscoring the extremely high demand for the asymmetric synthesis of (1R,2S)-vinyl-ACCA. This work presents a comprehensive overview of methods that have been developed to date for the preparation of (1R,2S)-vinyl-ACCA and its optical isomers. The presented data are grouped in three sections based on the biocatalytic, catalytic, and stoichiometric source of chirality. Aspects of operational convenience, practicality, and scalability are critically discussed.