Synthesis Of Tumor-Associated Carbohydrate Antigen KH-1 By Light-Promoted One-Pot Glycosylation Protocol

Tumor-associated antigen KH-1 was isolated from human colonic cancer cells,and has been shown to be over-expressed in human adenocarcinomas.The studes showed that the vaccine of KH-1 conjugated with Keyhole limpet hemocyanin(KLH)can evoke immune response targeting marker of adenocarcinoma,and is promising in clinic application.Although the Carbohydrate antigen KH-1 has been synthesized with different methods,its synthesis usually has disadvantages such as long synthetic steps,low yield,and more time to purify intermediates.Therefore,it is necessary to develop new efficient synthesis of KH-1 cabohydrate antigen.Carbohydrate chemists have continued to work on glycosylation methods and strategies.The pre-activation one-pot Oligosaccharide synthesis strategy proposed by our research group uses a single activation system throughout the synthesis operation,and does not need to rely on the “armed/disarmed” principle to regulate the activity of leaving groups and structural modules,greatly simplifying the oligosaccharides.Synthesis.Recently,the UV-mediated glycosylation method developed by our group has high efficiency,simple operation,and controllable process,it does not require quenching after the reaction,and can be used for pre-activation strategy.Therefore,UV-mediated activation-based one-pot oligosaccharide synthesis is powerful approach to oligosaccharide synthesis.Using commercialy available monosaccharides and lactose as starting materials,we synthesized 5 sugar building blocks via 5-10 steps;then,based on these blocks,we successfully constructed the core hexasaccharide structure of KH-1 carbohydrate structure antigen by light-promoted pre-activation based one-pot oligosaccharide synthesis;then selectively removed three temporary protective groups at three different sites to obtain the hexasaccharide with three hydroxyl exposed,and connected three fucose at a time to the core structure;and finally,after a series of deprotection operations,the KH-1 nonasaccharide was afforded.Our synthesis has laid a foundation for its studies on the biological activities of KH-1 and its derivatives.