Synthesis of chiral N-protected-amp;agr;-substituted-glycine free acids by zinc-mediated addition of organic halide to glycine cation equivalent

摘要

A method is described for synthesis of N-Boc-L- propargylglycine, a key intermediate used in the preparation of high- potency, orally-active renin inhibitors. This method involves reaction of an organic halide with a glycine cation equivalent, such as methyl N-Boc- 2-acetoxyglycine, in the presence of zinc dust to give Boc-protected amino acid derivatives in high yield. Typically useful organic halides are allylic, benzylic and propargylic halides. Resolution of methyl N-Boc- propargylglycine with . alpha.-chymotrypsin provides N-Boc-L- propargylglycine in high yield.