Development of alkyl imidate glycosylation method and application to allyl Lewis A synthesis

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Cheng, Anderson

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University of Guelph

Abstract

Glycosylation of 4-OH of 'N'-acetylglucosamine is difficult due to the low reactivity of the alcohol in this position. This complicates our efforts in designing anticancer vaccines based on tumor associated carbohydrate antigen Lewis A-Lewis X and dimeric Lewis X. We demonstrated that acceptors with alkyl imidate protecting on C-2, which were synthesized by treatment with 0.5 M MeOTf, glycosylated with thioglycoside or trichloroacetimidate donors in good yields (62-81%). To test for cross-reactivity of Lewis A analogs previously synthesized in the lab, we have synthesized allyl-Lewis A trisaccharide in 6% overall yield over 15 steps. After the synthesis of disaccharide acceptor, direct glycosylation with this acceptor did not afford the desired trisaccharide. However, using the alkyl imidate glycosylation method, fully protected trisaccharide was synthesized in 62% over 3 steps. Four-step deprotection afforded allyl Lewis A trisaccharide in 92%. This trisaccharide will be conjugated to BSA and used in ELISA testing.

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glycosylation, 'N'-acetylglucosamine, anticancer vaccines, acceptors, alkyl imidate, allyl-Lewis A trisaccharide, synthesis, disaccharide acceptor, acceptor, trisaccharide

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