Chemical Synthesis of Asparagine-Linked Archaeal N-Glycan fromMethanothermus fervidus

Abstract

Several N-linked glycoproteins have been identified in archaea and there is growing evidence that the N-glycan is involved in survival and functioning of archaea in extreme conditions. Chemical synthesis of the archaeal N-glycans represents a crucial step towards understanding the putative function of protein glycosylation in archaea. Herein the first total synthesis of the archaeal L-asparagine linked hexasaccharide from Methanothermus fervidus is reported using a highly convergent [3+3] glycosylation approach in high overall yields. The synthesis relies on efficient preparation of regioselectively protected thioglycoside building blocks for orthogonal glycosylations and late stage N-aspartylation.