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

Abstract

An efficient solid-phase synthesis of Fmoc (glyco)peptide thioesters is described. Fmoc·Ser·OAll and Fmoc·Thr·OAll 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 el. © 2002, Taylor & Francis Group, LLC. All rights reserved.