Total synthesis of C-α-Mannosyl tryptophan via palladium-catalyzed C-H glycosylation

Abstract

The C2-α-mannosyl-tryptophan amino acid is produced by a unique posttranslational modification (PTM) of proteins and poses a significant synthetic challenge. A new strategy based on Pd-catalyzed auxiliary-directed remote C-H glycosylation of tryptophan was developed, which generates the C2-α-mannopyranose (Man)-Trp unit in a highly efficient and stereoselective fashion. Density functional theory (DFT) computational studies support a concerted oxidative addition mechanism for the stereo-specific functionalization of a Pd(II) palladacycle intermediate with an α-mannosyl chloride donor. The utility of this method was demonstrated in the first total synthesis of insect C-glycopeptide hormone Cam-HrTH-I.