Stereoselective Synthesis of Peptidomimetics Based on Acid-catalyzed Ring-opening of β-Aziridinyl-α,β-enoates

Abstract

Introduction (E)-Alkene dipeptide isosteres (EADIs) are potential peptidomimetics, which involve backbone replacements of amide bonds in peptides. In the past several years, we have reported that ring-opening reactions of N-arylsulfonylaziridines bearing α,β-unsaturated esters are useful for the stereoselective synthesis of EADIs in the combinational use with organocopper (or organozinc-copper)-mediated anti-SN2’ reactions [1-3]. Regioand stereo-selective ring-opening reactions of Narylsulfonylaziridines bearing α,β-unsaturated esters by hard acids such as TFA, methanesulfonic acid and HCl have been reported by us. In the present study, treatment of these β-aziridinyl-α,β-enoates with alcohols, thiols or weak acids such as AcOH in the presence of Lewis acids was examined. The reactions of βaziridinyl-α,β-enoates having no side chain group at the δ-position were also investigated. In addition, the ring-opening reactions were conducted on solid supports and also applied to the stereoselective synthesis of EADI-containing peptidomimetics.