Synthesis of Reversed C-glycopeptide Mimics Monomer from Galactose via Passerini Reaction

C-glycopeptidomimetics are formed by the condensation of sugar unit and analogues of amino acid residue which generates a new carbon-carbon sigma bond. In glycopeptides, this condensation occurs in side chain of amino acid but introduction of isonitrile moiety on N-terminal of amino acid mimic unit can also be a route to produce such compounds. It is observed that C-glycopeptidomimetics are more stable than their N- and O-analogues under physiological conditions but their synthesis is a challenging task due to relatively less reactive C-6 position of hexose. In present work, synthesis of reversed C-glycopeptidomimetics (pseudoglycopeptides) was done by Passerini reaction protocol which is famous for peptide synthesis due to its mild conditions and easy workup. This paper discusses the use of α-D-galactose, a cheap and easily available monosaccharide to prepare reversed C-glycopeptidomimetics. The term reversed C-glycopeptidomimetics is derived for its analogy with reversed C-nucleosides, as in these reactions, instead of anomeric carbon i.e. more reactive site, C-6 undergoes to produce desired products.

Muhammad Atif Jalib, Muhammad Nabeel, Firdous Imran Ali, Ahmed Bari, Syed Ghulam Musharraf and Imran Ali Hashmi