Solid phase synthesis of a glycopeptide analogue using the acid sensitive 4-methoxybenzhydryl bromide resin

A convenient solid phase synthesis of a Thrombin Receptor Glycopeptide Mimetic analogue namely, 1-O-Methyl-2-N-{1'-(argininocarbonyl)-4'-[(4''-fluoro)-benzylamido]-cyclohexane}-glucosamine using Fmoc/tBu methodology and the 4-Methoxybenzhydryl bromide resin is described. The synthesized analogue was purified by Reverse Phase High Performance Liquid Chromatography (RP-HPLC) and was identified by Electron Spray Ionization-Mass Spectrometry (ESI-MS) and Nuclear Magnetic Resonance (NMR). The synthetic protocol introduced for the first time successfully the acid sensitive 4-Methoxybenzhydryl bromide resin as a scaffold for the synthesis of glycopeptides resulting in high yield reactions. This synthetic procedure could be a general one for the convenient synthesis of such glyco compounds as the method was used for the first time to glycosylate a non peptide mimetic of an important protein sequence, in particular of the thrombin receptor active site S42FLLR46.