Study On The Methodology Of Constructing ? And ?-KDO Glycosidic Bonds With A Mild I^? Reagent Activation And KDO Enose As A Donor

The sugar 3-deoxy-D-manno-oct-2-ulosonic acid(KDO)is a characteristic component of bacterial lipopolysaccharide(LPS,endotoxin)as well as Gram-positive bacteria capsule polysaccharide(CPS).The number of KDO units present in LPS,the way they are connected,and the occurrence of other substituents account for structural diversity of the inner core region of endotoxin.KDO is crucial to the viability and growth of bacteria cells.Therefore,the synthesis of KDO glycosides are desired and necessary.Natural KDO glycosides exist in either ?-or ?-anomeric configurations,mainly a configuration.KDO residues are of particular biomedical importance and extremely high cost of KDO isolation from natural sources.As a result,the chemical synthesis of KDO-containing oligosaccharides is currently appealing.The presence of a carboxylate group at the C1 position,which is electron withdrawing,leads to less stability of oxocarbenium and affects the reactivity of the donor;Due to the absence of a hydroxyl group at the C3 position,the classical neighboring group participation method is not applicable to the synthesis of KDO glycoside,a mixture of ?/? isomers are produced.Furthermore,Glycosylation reactions of KDO donors are impaired by facile formation of a 2,3-dehydro product(glycal ester),resulting in poor to modest yields of many cases.In this thesis,based on the previous work of our research group,the di-O-isopropylidene derivative of KDO ethyl ester was prepared in three steps on a scale of more than 40 g in one batch without any intermediate purifification.From this di-O-isopropylidene derivative of KDO ethyl ester,a set of KDO glycals(protected by isopropyl,benzyl,acetyl,carbonate,phenylboric acid,silyl)were synthesized quickly in high yield,and employed in glycosylations reactions with different iodonium(I)reagents.All glycosylations were performed by employing 1 equivalent of the donor and 1.5 equivalents of the acceptor in the presence of N-iodosaccharin(NISac,1.5 equiv.)and catalytic trifluoromethanesulfonic acid(TfOH,5%equiv.)at rt for 15-30 min,giving 3-iodo-KDO glycosides in good to excellent chemical yields with stereoselectivity.The iodo group was removed by utilizing a EosinY as photoredox catalyst and readily available dihydropyridine as hydrogen source under blue LED irradiation and 3-deoxy-KDO glycosides were obtained in excellent yields.