Glycosylation Of 2,4-Hydroxy Mannosides And Galactoside Acceptors And Their Regioselective Control

In recent years,the important role of oligosaccharides and glycoconjugates in biology has gradually been discovered with the deepening of biological research.The synthesis and preparation of oligosaccharides and glycoconjugates with clear structures have become the main tasks of glycochemistry research,because they can be used as molecular tools to meet the needs of biology research.It is inevitable to encounter the problem of how to control the acceptor coupling site in the synthesis of oligosaccharides,due to the presence of multiple hydroxyl on the glycosyl acceptor,which can be used as potential sites for glycosylation coupling.For this problem,the traditional method is to use the protecting group strategy;and using the difference of acceptor hydroxyl activity,adopting less protected or unprotected acceptor coupling strategy(regioselective strategy)has become one of the hotspots in recent years.Although glycochemists have achieved a lot of results in the regioselective glycosylation of glycosyl acceptors containing two or more hydroxyl groups,the application of oligosaccharide synthesis is still very limited,due to the difference in the activity of the hydroxyl groups on the sugar ring is indeed very small.Especially,the studies about regioselective glycosylation of 2,4-OH glycosyl acceptors are few.Therefore,this article mainly studies about the regioselectivity glycosylation of 2,4-OH mannosides and galactosides acceptors: changing 3-OH,6-OH and the end protecting groups of the mannosides and galactosides and making the 2,4-hydroxyl activity of the acceptor different by the influence of the protective group are used to study the regioselectivity of 2,4-OH in the glycosylation process under the influence of different protecting groups.First,2,4-OH glycosyl acceptors 40～55 are designed and synthesized whose 6-OH is protected by OTBDPS or OBn,3-OH is protected by OBz,OPiv or OBn,and the 1-OH is protected by OMP,OMe or OPNP.These glycosyl acceptors were respectively subjected to glycosylation reactions with donors 60-80 of different types,different configurations and different protective groups,and the regioselectivity of 2,4-OH was investigated.Finally,we found that the galactoside acceptor 45 and mannoside acceptor 55 have the best selectivity of 2-OH,whose 6-OH are protected by OTBDPS,3-OH are protected by OBn,and the end are protected by OMP.Later,the donor expansion of different sugar configurations(glucose,galactose,mannose,lactose and rhamnose)proved its wide applicability.In addition,it has also been found that the activity of the donor also has a significant impact on the selectivity of 2,4-OH: too low donor activity results in the inability to carry out glycosylation reaction,and too high activity will generate trisaccharide products and reduce the selectivity,which make the yield of disaccharides reduced.Therefore,it is necessary to find a suitable active donor to react with the corresponding acceptor to obtain the disaccharide product with high yield and high selectivity.In this way,the problem of how to design donor and acceptor in oligosaccharide synthesis is solved and a new method is developed for regioselective glycosylation strategies.