Synthetic oligosaccharides and glycoconjugates are increasingly used as probes for biological research and as lead compounds for drug and vaccine discovery. These endeavors are, however, complicated by a lack of general methods for the routine preparation of this important class of compounds. Recent development such as one-pot multi-step protecting group manipulations, the use of unified monosaccharide building blocks, the introduction of stereoselective glycosylation protocols, and convergent strategies for oligosaccharide assembly, are beginning to address these problems. Furthermore, oligosaccharide synthesis can be facilitated by chemo-enzymatic methods, which employ a range of glycosyl transferases to modify a synthetic oligosaccharide precursor. Glycosynthases, which are mutant glycosidases, that can readily form glycosidic linkages are addressing a lack of a wide range glycosyltransferases. The power of carbohydrate chemistry is highlighted by an ability to synthesize glycoproteins.

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Opportunities and challenges in synthetic oligosaccharide and glycoconjugate research

Carbohydrates are involved in a wide range of biological processes. These structurally diverse compounds are more complex than other biological polymers, and are often present as heterogeneous mixtures in nature. The chemical synthesis of carbohydrates is one way to obtain pure oligosaccharides, but it is hampered by difficulties associated with the regioselective protection of polyhydroxyls and challenges related to the stereoselective assembly of glycosidic linkages. Here we describe a combinatorial, and highly-regioselective, method that can be used to protect individual hydroxy groups of a monosaccharide. This approach can be used to install an orthogonal protecting group pattern in a single reaction vessel (a 'one-pot' reaction), which removes the need to carry out the time-consuming isolation and purification of intermediates. Hundreds of building blocks have been efficiently prepared starting from d-glucose, and the iterative coupling of these building blocks enabled us to assemble beta-1,6-glucans and a library of oligosaccharides based on the influenza-virus-binding trisaccharide.

Regioselective one-pot protection of carbohydrates

Carbohydrate mimetics-based glycosyltransferase inhibitors.

Carbohydrate microarrays - a new set of technologies at the frontiers of glycomics.

Therapeutic vaccines derived from carbohydrate antigen-adjuvant combinations are a promising approach for cancer immunotherapy. One of the critical limitations in this area is access to sufficient quantities of tumour-associated carbohydrate antigens and glycoconjugate adjuvants. At present, availability of the complex oligosaccharide constructs that are needed for the systematic design and evaluation of novel vaccine formulations relies on de novo chemical synthesis. The use of both state-of-the-art and emerging glycosylation technologies has led to significant advances in this field, allowing the clinical exploration of carbohydrate-based antigens in the treatment of cancer.

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Chemical glycosylation in the synthesis of glycoconjugate antitumour vaccines

Programmable One‐Pot Oligosaccharide Synthesis.

A short and effective synthesis of N-linked di- and trisaccharides is described. In a high-yielding reaction sequence, the glucosamine derivative 1 was transformed to the 3-azido-2,3-dideoxy sugar ...

Synthesis of a New Class of N-Linked Lewis and LacNAc Analogues as Potential Inhibitors of Human Fucosyltransferases: A General Method for the Incorporation of an Iminocyclitol as a Transition-State Mimetic of the Donor Sugar to the Acceptor

Chemoenzymatic synthesis of iminocyclitol derivatives: A useful library strategy for the development of selective fucosyltransfer enzymes inhibitors

Synthesis of a New Class of N-Linked Lewis and LacNAc Analogues as Potential Inhibitors of Human Fucosyltransferases: A General Method for the Incorporation of an Iminocyclitol as a Transition-State Mimetic of the Donor Sugar to the Acceptor.

A chemoenzymatic strategy has been developed for the synthesis of libraries of iminocyclitol derivatives for the discovery of new and selective fucosidase inhibitors.

Ralf Wischnat

Papers

Programmable One‐Pot Oligosaccharide Synthesis.

Synthesis of a New Class of N-Linked Lewis and LacNAc Analogues as Potential Inhibitors of Human Fucosyltransferases: A General Method for the Incorporation of an Iminocyclitol as a Transition-State Mimetic of the Donor Sugar to the Acceptor

Chemoenzymatic synthesis of iminocyclitol derivatives: A useful library strategy for the development of selective fucosyltransfer enzymes inhibitors

Synthesis of a New Class of N-Linked Lewis and LacNAc Analogues as Potential Inhibitors of Human Fucosyltransferases: A General Method for the Incorporation of an Iminocyclitol as a Transition-State Mimetic of the Donor Sugar to the Acceptor.

Chemoenzymatic Synthesis of Iminocyclitol Derivatives: A Useful Library Strategy for the Development of Selective Fucosyltransfer Enzymes Inhibitors.