Gold(?)-Catalyzed Glycosylation With Glycosyl Ynenoates As Donors And Studies On The Synthesis Of 32mer Polymannoside And Cyclic 32mer Polymannoside

Carbohydrates have important biological functions and play an indispensable role in a variety of biological activities.Polymannosides have strong immunological functions and various biological activities such as anti-oxidation and anti-inflammatory.Cyclic oligosaccharides own unique host properties,which can be taken advantage elegantly to form stable host-guest supramolecular complexes.Naturally-occurring cyclic glycans such as cyclodextrin and its derivatives are widely used as carriers for delivery of small-molecule drugs and so on.However,the types of natural cyclic glycans are quite limited.Moreover,the functions of non-natural cyclic glycans are unclear.In order to further study the structures and functions of these polysaccharides and cyclic glycans,it is necessary to obtain sufficient amounts of pure and well-defined polysaccharides and cyclic glycans.Although a few efficient approaches for the synthesis of glycans have been developed,so far,no glycosylation method is applicable to the construction of all types of glycosidic bonds.In addition,the chemical synthesis of polysaccharides remains to be a challenging task.For example,the couple of polysaccharide fragments is very difficult due to the unique three-dimensional structure of polysaccharides,and subsequent deprotection and purification further increases the difficulties;macrocyclization of pre-formed linear oligomer faces low efficiency and poor stereoselectivity,especially the synthesis of large cyclic oligosaccharides having ten or more sugar moieties is quite difficult.Therefore,it is of great significance to develop new and efficient glycosylation methods and apply them to the synthesis of polysaccharides.In the first part of this paper,a simple and versatile gold(?)-catalyzed glycosylation with both armed and disarmed glycosyl ynenoates as donors has been developed.The present glycosyl ynenoates are structurally simple,bentch-stable and can be flexibly prepared.Furthermore,the new glycosylation protocol with glycosyl ynenoates as donors possesses a very wide substrate scope.Notably,the present ynenoate donors are proved efficient in the synthesis of oligosaccharides via the latent-active strategy and the multiple orthogonal one-pot strategy.Finally,this approach is successfully applied to the formal synthesis of the tetrasaccharide hapten of Streptococcus pneumoniae serotype 3.In the second part of this paper,the newly developed gold-catalyzed glycosylation reaction with glycosyl ynenoates as donors has been successfully applied to the highly efficient synthesis of ?-(1?6)-32mer polymannoside,confirming the practicability of this method.Based on the orthogonal and consecutive activation of glycosyl ynenoates and thioglycosides,the highly convergent synthesis of the 32mer polymannoside is accomplished within five[2n+2n]glycosylation reactions.Subsequently,the equipment of linker at the reducing end of 32mer polymannoside and global deprotection is completed,which lays the foundation for its potential biological activity tests.In the last part of this paper,based on the macrocyclization of pre-formed bifunctional 32mer polymannosyl ynenoate,cyclic 32mer polymannoside,the largest cyclic polysaccharide so far,is efficiently synthesized.Meanwhile,a series of cyclic mannan oligosaccharides including cyclic di-,tetra-,octa-and hexadecasaccharide are synthesized.The synthesized cyclic mannans lay a foundation for the research on their functions and application of delivery system of biomacromolecular drugs.