Studies On The Glycosylations Using Glycosyl Phosphonates As Donors And Synthesis Of11-deoxyheloside A

Oligosaccharides and glycoconjugates are “biological information” bearers in thecomplicated biological processes of human, being widely present in all kinds oforganisms. Glycosylation is the most important and basic reaction in the synthesis ofoligosaccharides and glycoconjugates. In the glycosylation reaction, the glycosyldonor is essential in building stereoselectively the glycosidic bond and a high yield ofglycoside product. People have developed many different glycosyl donors, such ashalosugar, glycosyl trichloroacetimidate donor, thioglycoside, glycosyl o-alkynylbenzoate donor and glycosyl phosphate donor and so on. Although these glycosyldonors have many advantages, no one can be applied universally. So developing anew glycosyl donor with better stereoselectivity, better reactivity and widerapplication is demanded.We synthesized eight glycosyl phosphonates by the reaction of phosphonic acidmonoethyl ester with glycosyl derivatives, which have varied protecting groups suchas Ac, Bn, Bz and so on. Then a series of glycosylations were explored on usingglycosyl phosphonates with different types of acceptors catalyzed synergistically by acatalytic amount of (4-MeOPh)3PAuB(C6F5)4and AgB(C6F5)4. Twenty-four glycosideproducts were obtained stereoselectively in50-99%yields. The glycosyl donor hasmany advantages, such as simple preparation, good stability and better activity. Thefeatures of its glycosylation are simple operation, mild reaction condition and highyield, etc. Phosphonate glycosyl donors further enrich the types of glycosyl donorsand lay the foundation for the synthesis of carbohydrate compounds.11-deoxyheloside A is an open-chain steroidal saponins. In2012, it was isolatedfrom Chamaelirium luteum. C. luteum is a traditional Chinese herbal medicine.11-deoxyheloside A is composed of two β-D-glucose and cholesteric alkyl-typesteroidal aglycone. The studies on pharmacological activity and related research of11-deoxyheloside A were hindered in many reasons, such as limited medicinal resources, low concentration and difficult process of separation and extraction. And sofar synthesis of11-deoxyheloside A was reported in no one paper.We intend to use a diosgenin derivative as the starting material. It was subjected toundergo Luche reduction, configuration inversion of22R-OH group in aglycone andacetylation to get the desired aglycone. Two β-D-glucoses were introducedstereoselectively to the aglycone by gold-catalyzed glycosylation of phosphonateglycosyl donor. Finally, synthesis of11-deoxyheloside A was finished for the firsttime with the longest linear8step reactions, in overall yield of17.9%. This workprovides synthetic preparation for its studies on pharmacological activity andstructure-activity relationship. And it is significantly instructive to the efficient andselective syntheses of a series of cholestan saponin compounds.