Studies On The Glycosylations Of Glycosyl4,5-Allenoates And Stereoselective Synthesis Of β-D-Mannuronic Acid Oligosaccharides

Oligosaccharides and glycoconjugates play an extremely important role in thebiological process, and their synthesis has gained more and more attention recently. Inthis paper, a novel glycosyl donor was developed, and three-mannuronic acidesters, an alginate trisaccharide and two tetrasaccharides, were also synthesized,which are important for their structure-activity relationships elucidation.Part1: Studies on the glycosylations of glycosyl4,5-allenoates as donorsGlycosylation is the focus and center of carbohydrate chemistry, and the donorsare of great importance to the stereoselectivity and yield of glycosylations. Alleneshave gained considerable attention due to their versatile reactivities and ability toundergo a variety of transformations. Chemists have converted4,5-allenoic acid intohalolactone through the activation of cumulated double bonds with I2or Ph3PAuOTf.In this paper, we present our research on the preparation and application of glycosyl4,5-allenoates in glycosylation reactions.We prepared total eight glycosyl allenoates by treating3,3-dimethyl-4,5-allenoicacid with different hemiacetals, which have varied protecting groups such as Ac, Bn,Bz and so on. Then a series of glycosylations were explored using the eight glycosylalloates and various acceptors, and eighteen glycoside products were obtained.Glycosyl allenoates as donors were easily prepared and their glycosylations could bepromoted by easy-to-handle and low-cost BDMS, and the enhanced reactivitycompared with glycosyl gem-dimethyl pentenoate makes them attractive donors forthe oligo-saccharide assembly.Part2: Stereoselective synthesis of-D-mannuronic acid oligosaccharidesAlginate oligosaccharides exhibit various biological properties including stimula- tion of growth, immunomodulation, antitumor, treating alzheimer’s, etc.-D-Mannur-oic acids, the fragments of alginate oligosaccharides, are difficult to construct in astereocontrolled manner, due to their anomeric effect and the effect of neighbouringgroup participation. In this paper, we have finished the synthesis of alginatetrisaccharides and tetrasaccharides, using glycosyl sulfoxides and glycosylortho-alkynyl benzoates respectively as donors.Glycosyl sulfoxides not only can be prepared easily, but also have enhancedreactivity and mild reaction conditions. In this paper, mannuronic acid sulfoxide97was prepared from D-mannose in36.3%overall yield via11steps, and then was usedas donors to synthesize tetrasaccharide109successfully via only two glycosylationsteps.At the same time,-D-mannuronic acid trisaccharide135was synthesized in36.5%overall yield thorough a linear stepwise synthesis strategy, with glycosyl ortho-alkynyl benzoates used as donors. Then tetrasaccharide137was obtained in a yield of52%after the glycosylation of glycosyl ortho-alkynyl benzoate118with trisaccharide136.