A concise synthesis of N-trichloroethoxycarbonyl lactosamine trichloroacetimidate donor and its application in the synthesis of Gal(β1-4)GlcNAc(β1-3)L-Fuc(α-OAII)

A large-scale practical approach is described for converting D-glucosamine into lactosamine donor. 2-Naphthylmethyl (NAP) functionality is utilized as anomeric protecting group of N-trichloroethoxycarboonyl (N-Troc) glucosamine, which can avoid an unexpected intermolecular aglycon transfer observed in TMSOTf-mediated glycosylation when using corresponding thioglycoside as glycosyl acceptor. N-Troc protected glucosamine 9 shows enhanced reactivity as glycosyl acceptor, which was confirmed by systemic comparison with various N-protected glucosamine derivatives in TMSOTf-mediated glycosylation. The lactosamine imidate 14 exhibits valuable glycosyl donor property for β-selective glycosylation which furnished the desired trisaccharide Gal(β1-4) GlcNAc(β1-3)L-Fuc(α-OAll) in high yield. This sequence is part of O-linked chains of human clotting factor IX and mammalian Notch 1, and it was also found to be required for fringe to inhibit Jagged1-dependent Notch activation.