Synthesis of a tristearoyl lipomannan via preactivation-based iterative one-pot glycosylation.

A convergent and efficient strategy was developed for the synthesis of lipomannan (LM), useful for vaccine development. Thioglycosides were employed as glycosyl donors to construct two key pseudotrisaccharide and tetramannose intermediates through preactivation-based glycosylation strategy. These building blocks were then successfully coupled to form the LM core, which was lapidated, phospholipidated, and finally globally deprotected to afford the target molecule. The intermediate LM core involved in this synthesis contained orthogonal protections, which would facilitate its variable modifications for the preparation of other complex LM derivatives and for the synthesis of LM conjugates as LM-based vaccines.