分子内redox反応を利用したフルオロアルケンジペプチドイソスターの合成 分子内redox反応を利用したフルオロアルケンジペプチドイソスターの合成

抄録

Replacement of naturally occurring peptide bonds with (Z)-fluoroalkenes affords potential dipeptide mimetics named (Z)-fluoroalkene dipeptide isosteres (FADIs). We have reported the synthesis of FADIs utilizing the intermolecular redox reaction of gamma, gamma-difluoro-alpha, beta-enoates with an organocopper or SmI₂. In this study, we aimed at intramolecular redox reaction using N-heterocyclic carbenes (NHCs) or cyanide anion for the preparation of FADIs. We assumed that nucleophilic attack of NHCs or cyanide anion to gamma, gamma-difluoro-alpha, beta-enoylsilanes should cause an S_N2'-type reductive elimination of fluoride anion followed by oxidation of the acylsilane unit to esters or amides in the presence of nucleophiles (alcohols or amines). Optimization of the reaction conditions resulted in the successful preparation of ester-type FADIs and amide-type FADIs.