Silyl linker-based approach to the solid-phase synthesis of Fmoc glycopeptide thioesters.

An efficient solid-phase synthesis of Fmoc (glyco)peptide thioesters is described. Fmoc (.) Ser (.) OAII and Fmoc (.) Thr (.) OAII bound to resin with a silyl ether linker were deallylated by Pd(0) catalysis and condensed with thiophenol, benzyl mercaptane, and ethyl 3-mercaptopropionate by activation with DCC/HOBt. The thioesters were released from the resin either by treatment with CsF-AcOH or by acidic hydrolysis. The effectiveness of this silyl linker strategy is further demonstrated by the synthesis of more complex (glyco)peptide thioesters 25, 26 and 27 involving N-->C and C-->N peptide elongation.