Ketomethylene pseudopeptide

The synthesis of ketomethylene pseudopeptide analogues was accomplished by L. Cheng et al., and their biological activity as thrombin inhibitors was tested. These analogues were prepared through a modified Dakin-West reaction under mild conditions and in almost quantitative yield. The required anhydride was prepared from monomethyl succinate, and a large excess of it was mixed with the tripeptide substrate in pyridine in addition to triethylamine and catalytic amounts of DMAP. The reaction mixture was heated for one hour at 40-50 °C. 

Acylation of 179 with 2,2-difluoro-3-methyl-4-pentenoic acid anhydride yields ot-amino ketones 180 that can serve as intermediates to prepare pseudopeptides such as peptidyl ot,ot-difluoroalkylketones 181 (Scheme 7.54) or ketomethylene pseudo-peptides. ... 

---