18 リピドAとその類縁体のアフィニティー分離法を利用した効率的な合成と機能(口頭発表の部)

概要

論文の詳細を見る
Lipid A is an immunostimulating glycoconjugate characteristic to gram-negative bacteria. In order to understand the role of the acyl moieties for the biological activity, the effect of distribution of acyl groups was systematically investigated. A new efficient route for the synthesis of lipid A and its analogs was hence established by using our new strategy, i.e., synthesis based on affinity separation (SAS), where compounds possessing a barbituric acid tag (BA) were selectively and rapidly purified by the aid of its interaction with an artificial receptor. After successful synthesis of E. coli lipid A by the SAS-strategy, a small library of lipid A analogs having a carboxymethyl (CM) group at the 1 position in place of the phosphate was synthesized. CM analogs had proved to exhibit biological activity indistinguishable with that of lipid A, but are chemically stable and are easier to synthesize than the latter. All the target structures possess hexaacyl groups with different acylation pattern: each has two (R)-3-hydroxydecanoyl groups and two (R)-3-(dodecanoyloxy)decanoyl groups. A suitably protected glucosamine α-carboxymethyl glycoside possessing the BA-tag was glycosylated with a 4'-phosphorylated glycosyl trichloroacetimidate to give a disaccharide, which was purified by the affinity separation. Successive removal of protective groups and introduction of acyl groups were then effected and the synthetic intermediate at each step was purified rapidly by the affinity separation. The final deprotection and cleavage of the tag by catalytic hydrogenolysis afforded the desired CM-analogues. Biological tests of them clearly demonstrated that the acylation patterns of the individual compounds determine the biological activity.
天然有機化合物討論会の論文
2002-09-01

18 リピドAとその類縁体のアフィニティー分離法を利用した効率的な合成と機能(口頭発表の部)

スポンサーリンク

概要

著者

関連論文

スポンサーリンク