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Carbohydrates have gained increasing appreciation over the last few decades for their fundamental roles in all essential areas of life. As a result, there has been a surge of activity in synthetic glycosylation strategies to construct useful oligosaccharides. This review evaluates the advances in synthetic carbohydrate chemistry, specifically preactivation methodologies, stereoselective β-mannosylations, and an automated, electrochemical preactivation method. Also discussed is the use of preactivation as a tool to study reactive intermediates, and applications of preactivation protocols in the one pot-synthesis of a hyaluronic acid decasaccharide and one-pot synthesis of a tristearoyl lipomannan containing a pseudotrisaccharide.

The cell envelope of mycobacterial species, which include the deadly Mycobacterium tuberculosis, carries unique glycan structures that are crucial for infection and bacterial survival. Notable among these glycans are the structurally-related phosphatidylinositol mannosides (PIMs), lipomannan, and lipoarabinomannan. The immunoactivities of these structures attracted considerable attention from synthetic chemists and biologists alike, who are keen on evaluating vaccine or adjuvant properties. Moreover, PIMs are interesting synthetic targets because of the regio- and stereoselective considerations in generating the inositol and mannosyl cores. In this paper, we summarize the recent efforts in the chemical synthesis of PIMs as well as their analogues. Particular emphasis is given on the challenges associated with the preparation of the chiral myo-inositol derivatives, the regioselective installation of mannosyl residues, and phosphatidylation strategies. The results of the bioevaluation of selected compounds are also briefly described.

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.

Covering: up to October 2009 The mannose-rich mycobacterial glycophospholipids phosphatidylinositol mannosides (PIMs), lipomannan (LM), and lipoarabinomannan (LAM) are important constituents of the mycobacterial cell wall and are critical mediators of host–pathogen interactions. Since the earliest reports of their existence almost 80 years ago, intensive efforts have now resulted in an almost complete description of their molecular structures. In parallel, based on studies over the last 10 years, their biosynthesis is now reasonably well understood. Owing to the structural complexity of these glycophospholipids, chemically synthesized fragments have been essential for dissecting their biosynthesis and biological functions. This review provides an overview of the synthesis of fragments of the PIMs, LM and LAM, and approaches to the total synthesis of PIMs and analogues. Also covered are uses of synthetic fragments, authentic structures and analogues as biochemical reagents and immunomodulators.