Carbohydrates are increasingly recognized as essential components for intercellular communication and as important potential targets for immunological applications. However, the acetal linkage in carbohydrates makes them highly suspectible to glycolytic cleavage and limits the utility of carbohydrate-based drugs and immunotherapies. This is especially relevant as the tumour-associated carbohydrate antigens (TACAs), some of which are only expressed on cancer cells, have drawn significant interest as targets for developing anticancer vaccines. One potential solution to overcome this low biostability is to replace the labile acetal linkage with an ether by substituting a methylene functionality for one of the glycosidic oxygens to create either carbasugars or C-glycosides. The resulting molecules have all shown remarkably more potent immunological activity than their natural acetal-containing analogues when tested, but there are still no reports regarding the immunological activity of acetal-free TF antigens, nor has a synthesis of a completely acetal-free TF antigen been disclosed. This presentation will describe our efforts towards accessing fully "acetal-free" disaccharide building blocks relevant for anti-cancer immunotherapies, and highlight the technical challenges in this field that require the attention of synthetic chemists. We will also report the first synthesis of a biologically active glycosphingolipid disaccharide isolated from <i>S. pneuomoniae</i> that may be the primary natural antigen for the invairant Natural Killer T-cell system. Synthetic and immunology aspects will be discussed.

Adventures in carbohydrate chemistry: Acetal-free carbohydrates, and the total synthesis of immunologically active glycolipids

255th National Meeting (2018)

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