100(P-48) 環内に硫黄原子を有するオリゴサッカリドの合成研究(ポスター発表の部)

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Glycosidase-resistant carbohydrate analogues, called glycomimetics, are very important molecular probes for investigation of glycosidase reaction mechanisms. Oligosaccharide mimics (≧triose) can be applied to endo-glycosidases of which reaction mechanisms have not been studied well due to the absence of suitable probes. In particular, oligothiopyranoses, analogues with sulfur atoms in place of tetrahydropyran oxygens, are anticipated to become potent competitive inhibitors against endo-glycosidases. By our preliminary molecular modeling studies, molecular size of an oligomer model with thioglycoside bonds (Type B in Figure 1.) is bigger than that of natural type. These suggested that oligomelization accumulates geometrical deviation caused by the structural alteration of each pyranose units. On the other hand, the modeling calculations show small difference in the molecular size between tetrakis-thiopyranose model (Type A) and the corresponding natural type model. It can be proposed that the ring structure of tetrahydrothiopyran absorb the deviations of both bond angles and bond lengths between ethers and thioethers. We thought oligothiosaccharides, like model Type A, can be potent competitive inhibitors against endo-glycosidases, and attempted synthesis of sulfur-substituted glycomimetics. Our investigation revealed that (i) combination usage of benzoyl- or pivaloyl-protected donors 4, 5 and BF_3・OEt_2 as a glycosyl promoter gave β-glycosides 15-20 stereoselectively when C6-OH glycopyranosyl derivatives 8-10 were employed as acceptors (Table 1., Run 5-10), (ii) glycosylations of Bn or MPM protected donors 24, 25 with various acceptors proceeded smoothly to afford α-glycosides stereoselectively (Table 2.), and (iii) acyl- and MPM protective groups of the glycosides 31, 32 can be removed efficiently by sequential basic hydrolysis and DDQ treatment without affecting thioethers those are labile under oxidation conditions. Those findings realized the synthesis of the sulfur-substituted isomaltotetraose and maltotriose analogues 1 and 2 effectively. Further, we also succeeded in the preparation of methyl and p-nitrophenyl 5'-thiogentiobioside (21, 22) as well as methyl 6-O-(5'-thio-β-glucopyranosyl)-α-galactopyranoside (23). Those glycomimetics would be applied to enzymatic studies.
天然有機化合物討論会の論文
2002-09-01

100(P-48) 環内に硫黄原子を有するオリゴサッカリドの合成研究(ポスター発表の部)

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