ブタからの肝臓移植を可能にするセラミド系糖脂質素材の設計とその合成

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It is known that hyper acute rejection (HAK) which interfere with the xeno-transplantation of organs was caused by excess immune responses between Gala (1,3) Gal antigenic glycoside of porcine liver and the antibody generated in the recipient serum toward the glycoside. In order to develop the novel medical materials for avoiding the HAR, we synthesized mycestericin D and F, potent immune suppressants isolated from Isaria sinclairii, and a UDP-galactose mimetic as an inhibitor of α1,3-galactosyltransferase that biosynthesizes the Galaα(1,3) Gal epitope.1) Synthesis of mycestericinsγBenzyloxybutanal was treated with L-threonine aldolase (from Candida humicola AKU 4586) that catalyzes aldol condensation in the presence of glycine to afford the ε-benzyloxy-α-L-amino acid, of which the methyl ester was transformed to an oxazoline derivative by the reaction with methyl benzimidate. After addition of the C-l unit to the α-orposition of the oxazoline derivative, of which the benzyl ether was transformed to an aldehyde group, the following Wittig reaction and deprotection gave mycestericin D. A subsequent hydrogenation step gave mycestericin F.2) Synthesis of peptidic mimetics of UDP-galactoseL-Threonine aldolase-catalyzed reaction of 2-(l-N-uracily])acetaldehyde and glycine afforded a uracil residue bearing β-hydroxy-α-L-amino acid, of which the benzyl ester was condensed with 2-(l-O-α-galactosyl) hydroxyacetic acid by the DCC / HOBt method to form a peptidic linkage. The following deprotection procedure provided the peptidic mimetics of UDP-galactose.