An efficient conversion
of hydroxyproline “customizable”
units into new amino acids with a variety of N-alkyl
substituents is described. The process is versatile and can afford
valuable N-methyl amino acids and N,O-acetals. In addition, it allows the introduction
of N-homoallylic substituents and N-chains with terminal
ester, ketone, or cyano groups. These chains could be used for peptide
extension or conjugation to other molecules (e.g., by olefin metathesis,
peptide ligation, etc.). The transformation is carried out in just
two (for R = CH2OAc) or three steps (scission of the pyrrolidine
ring, manipulation of the α-chain, and the N-substituent) under mild, metal-free conditions, affording products
with high optical purity.