Abstract
Several C-terminal peptidyl-substituted bis- and tris(electrophiles) were prepared by starting from polymeric phosphoranylidenacetates as acyl anion equivalents. After C-acylations with amino acids and peptide elongation, the obtained peptidyl-phosphoranylideneacetate resins were either cleaved oxidatively, delivering peptidyl-diketo esters, or saponified, leading to immediate decarboxylation. The generated peptidyl-phosphorane could be treated with aldehydes to yield peptidyl vinyl ketones or could be cleaved oxidatively to yield peptidyl keto aldehydes. Ligation with various bis(nucleophiles) including hydrazines, hydroxylamine, diamines, amino-thiols, amidines, and guanidines were investigated in the formation of peptide-heterocycle chimera containing pyrazoline, pyrazole, isoxazole, isoxazoline, thiazepine, quinoxaline, and imidazolone heterocycles.