Total Synthesis of C-α-Mannosyl Tryptophan via Palladium-Catalyzed C-H Glycosylation

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 stereospecific functionalization of a Pd(II)palladacycle intermediate with anα-mannosyl chloride donor.The utility of this method was demonstrated in the first total synthesis of insect C-glycopeptide hormone Cam-HrTH-I.