Multicomponent Synthesis of Peptide-Sugar Conjugates Incorporating Hexafluorovaline

The development of new methods for linking sugars to peptides or proteins is an active area of research because natural glycopeptides or neoglycoconjugates play important roles in biology and medicine and are indispensable tools for probing several biological processes. Herein we report a novel one-pot, three-component process for the synthesis of peptide-urea conjugates incorporating a hexafluorovaline residue under very mild conditions and high yields using commercially available starting materials such as carbodiimides, alpha-amino acid derivatives and 4,4,4-trifluoro-3-trifluoromethylcrotonic acid. The reaction has been exploited for the synthesis of a library of structurally diverse peptide-sugar conjugates incorporating hexafluorovaline through a four-component, one-pot sequential process by generating the carbodiimides in situ from easily accessible sugar containing azides and commercial available isocyanates through the Staudinger (aza-Wittig) reaction.