Tashiro Takuya, Nakagawa Ryusuke, Hirokawa Takatsugu, Inoue Sayo, Watarai Hiroshi, Taniguchi Masaru, Mori Kenji
Glycosphingolipid Synthesis Group, Laboratory for Immune Regulation, Research Center for Allergy and Immunology, RIKEN, Hirosawa 2-1, Wako-shi, Saitama 351-0198, Japan.
Bioorg Med Chem. 2009 Sep 1;17(17):6360-73. doi: 10.1016/j.bmc.2009.07.025. Epub 2009 Jul 18.
Cyclitol [RCAI-37 (1), 59 (5), 92 (7), and 102 (2)] and carbasugar analogs [RCAI-56 (3), 60 (4), and 101 (6)] of KRN7000 were synthesized through coupling reactions of the corresponding cyclitol or carbasugar derivatives with a cyclic sulfamidate (9) as the key step. Bioassay showed RCAI-56 (3, carbagalactose analog of KRN7000), 59 (5, 1-deoxy-neo-inositol analog), and 92 (7, 1-O-methylated 5) to be remarkably potent stimulants of mouse lymphocytes to produce Th1-biased cytokines, such as interferon-gamma, in vivo. RCAI-60 (4, carbafucose analog) and RCAI-101 (6, 6-O-methylated 3) showed strong bioactivity, on the other hands, RCAI-37 (1, myo-inositol analog) and 102 (2, neo-inositol analog) induced little cytokine production.
通过相应的环醇或碳环糖衍生物与环氨基磺酸酯（9）的偶联反应作为关键步骤，合成了KRN7000的环醇[RCAI - 37（1）、59（5）、92（7）和102（2）]和碳环糖类似物[RCAI - 56（3）、60（4）和101（6）]。生物测定表明，RCAI - 56（3，KRN7000的碳环半乳糖类似物）、59（5，1 - 脱氧新肌醇类似物）和92（7，1 - O - 甲基化的5）在体内是小鼠淋巴细胞产生Th1偏向性细胞因子（如干扰素 - γ）的显著有效刺激物。另一方面，RCAI - 60（4，碳环岩藻糖类似物）和RCAI - 101（6，6 - O - 甲基化的3）表现出较强的生物活性，而RCAI - 37（1，肌醇类似物）和102（2，新肌醇类似物）诱导的细胞因子产生很少。
