| The viability of carbohydrate-based immunotheraphy has increased greatly with the realization that aberrant expression of specific oligosaccharide motifs on the surface of tumor cells permits differentiation from normal cells. However, an intrinsic problem associated with glycopeptides as cancer vaccines is the hydrolytic instability of the carbohydrate antigen linkage to the immunostimulating peptide. A potential solution is the synthesis of C-glycopeptide analogues where the carbohydrate-peptide ether linkage is replaced with a carbon chain spacer. The use of C-allyl derivatives would allow for both co- and post-translational synthesis of the desired C-glycoconjugates.; Initially, a systematic exploration of C-allylation by the sulfoxide method was pursued in an attempt to develop a convergent method for stereoselective C-glycosidic bond formation. While high stereoselectively was achieved in the synthesis of alpha-C -allyl glucosides, beta-C-allyl glucosides were obtained with modest anomenc excess. When the reaction conditions were applied to various saccharides, similar stereoselectivities were observed.; A beta-C-allyl lactose core common to the GM 3, Fucosyl GM1, and PK glycolipid antigens was prepared by use of a Weinreb amide intermediate. Significant progress towards an efficient synthesis of beta-C-allyl analogues of the GM3 and PK antigens has been made. Furthermore, an optimized synthetic route for the fucosyl trisaccharide portion of the Fucosyl GM1 antigen employing iterative activation of thioglycosides was begun.; Finally, the synthesis of a C3,C4,C6-orthogonally protected alpha- C-allyl N-acetylgalactosamine (Tn antigen) has been achieved by C4 inversion of a 4-O-triflyl glucosamine. This provides potential access to alpha-C-allyl analogues of the more complex members of the glycophorin family of glycopepude antigens. |
