Peptidoglycan (PGN) is a major component of bacterial cell wall and has been known as a potent immunostimulant. PGN is recognized by various proteins including the innate immune receptors, Nod1 and Nod2, peptidoglycan recognition proteins (PGRPs), and other PGN recognizing enzymes and lectins. We have developed the synthetic methods of PGN fragments for the functional analysis of these proteins.¹⁾

In the present study, we developed a solid phase synthesis of PGN fragments on JandaJel^TM-Wang resin. We used glycosyl trifluoroacetimidates as the glycosyl donors and Fmoc group for the temporary protection of the 4-hydroxy group of the glycosyl acceptors. The glycan part was introduced to Wang resin by glycosylation using TMSOTf as a catalyst. THF-CH₂Cl₂ was used for the solvent for glycosylation to suppress the acidity of TMSOTf and prevent the cleavage of glycan from the resin during the glycosylation. We observed that the addition of a fluorous solvent, C₄F₉OEt, promoted the glycosylation on the solid-support owing to the “reagent concentration effects”. The capping with acetyl group on un-reacted hydroxy group was critical for glycan elongation; Ac₂O, imidazole, and DMAP•HCl was used since O-Fmoc group was stable under this condition but partly cleaved with Ac₂O-pyridine. After construction of the glycan part, the peptide chain was introduced. The protected peptidoglycan fragments were readily cleaved by diluted TFA from the resin. The final deprotection of them is now under investigation.