Efficient Synthesis Of Sialic Trisaccharide 3'-SLN Through Stereoselective Glycosylation Of Diol And Polyol Acceptors

The selective glycosylation strategy has been a hot topic in organic chemistry,especially in sugar chemistry.A variety of natural products have been synthesized by glycosylation,and sialic acid plays an extremely important role in living bodies.N-acetylneuraminic acid(Neu5Ac)is the most widely distributed sialic acid compound in nature and can be used to synthesize sialic acid oligosaccharides of important biological significance.Sialylated oligolactosamine glycan(3'-SLN)is one of the typical oligosaccharides,and its Neu5 Ac end-group structure plays a key role in the specific recognition between cells.However,the synthesis of the natural product lacks a simple and efficient means.In order to further study the biological function of sialic acid,it is necessary to develop an effective synthesis line of highly stereoselective sialylated oligolactosamine glycan chains.We mainly do the following researches:1.During the synthesis of amino lactose,the conditions for the glycosylation process were screened,and the use of different 6-C-protecting groups and terminal-end protecting groups as glycosyl acceptors was attempted to obtain the optimal glucosamine protecting group: 1-position Glycosylation of galactose with p-methoxyphenyl,2-position phthaloyl,and 6-position tert-butyldiphenylsilyl with galactose at 1-position of trichloroacetimid in a high yield of up to 92% N-acetyllactosamine derivatives.2.The effects of different protecting groups on donors on the glycosylation results were studied.Different donors were subjected to glycosylation under optimal conditions and optimal glycosyl acceptors.The results confirmed the glycosylation chemistry of diols.Selectivity is not only related to the protecting group on the receptor,but also related to the protecting group on the glycosyl donor.When the protecting group on the donor has a strong armed protective group similar to the tert-butylsilyl group or the benzyl group,the activity of the donor is increased to attack the hydroxyl group at the lower position of the receptor.In the glycosylation reaction at the 3-position hydroxyl group,a single beta configuration may be involved in the role of the remote phthaloyl group at the 2-position of the phthaloyl group on the receptor.3.In the process of sialylation of amino lactose,we first carried out complex protection and deprotection processes,such as benzylation,peracetylation,debenzylation and 3-selective acetylation,pivalidylation,deacetylation reactions in order to expose the 3-position hydroxyl group on the disaccharide galactose fragment.But the results are not ideal,and then we found that phosphorous acid-protected sialic acid can interact with polyhydroxyl of galactose under the action of TMSOTf.Selective glycosylation was performed while the reaction conditions were screened.Phosphite sialic acid is cheaper to prepare.And more importantly,the synthesis method is simple and does not require complicated protection and deprotection of the receptor.We have successfully synthesized a 3'-SLN derivative from the beginning of glucosamine using this method.The hydrochloride salt was started and the product was synthesized in 10-step reaction conditions.The total yield was 18.5%,which greatly improved the yield.