P-38 ウレアグリコシド結合をもつ人工糖ペプチド・オリゴ糖の合成研究(ポスター発表の部)

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A novel approach to the synthesis of Fmoc-protected neoglycopeptide building blocks is described. Oxidaiton of N-acetyl-D-glucosamine isonitrile 11 afforded highly reactive glycopyranosyl isocyanate 12, which reacted with amino acid derivatives, 13 and 14, to furnish the corresponding urea- and carbamate-linked Fmoc-protected N-acetyl-D-glucosamine amino acid conjugates, 15 and 16 in good yields. We have also demonstrated that a novel approach to the synthesis of urea glycosides in aqueous media. In fact, Steyermark's glucopyranosyl oxazolidinone 19 was found to be a good synthon for anchoring glucosyl moieties onto amines. The present method was successfully applied to establish a new route for the synthesis of urea-tethered pseudooligosaccharides in water. The synthesis of urea-linked analouges of cellobiose and lactose has been established. The key featurue in the present synthesis is the use of strained bicyclic oxazolidinones 19 and 22. Although galactose-type 22 was much more reactive than glucose-type 19 due to the presence of axial C-4 hydroxy group, it is fortunate that Steyermark-type oxazolidinone 22 is not so labile as to become hydrolyzed on its way toward the amines. The synthesis of urea-tethered pseudopentasaccharide began with the Staudinger reaction of azide 29 with triphenylphosphine in a mixture of water and t-butylalcohol (Scheme 6). The resultant amine 30 was dissolved in aqueous media (H_2O/MeOH, 1: 2) and then treated with 1.5 equiv of lactosyl oxazolidinone 31. The formation of β-(1→6) urea-intersaccharide bond was completed at room temperature within 24h. Hydrogenolysis of the Cbz-group in 32 gave the amine 33, which was subsequently subjected to the second urea-glycosylation with cellobiosyl oxazolidinone 34 in water. The reaction mixture was stirred at room temperature for 24h, and then loaded on the reversed phase column chromatography to furnish urea-linked pseudopentasaccharide 35 in 73% overall yield starting from 29. It should be noted that the whole procedure in this reaction sequence (29→35) was carried out in a one-pot operation.
天然有機化合物討論会の論文
2006-09-15

P-38 ウレアグリコシド結合をもつ人工糖ペプチド・オリゴ糖の合成研究(ポスター発表の部)

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