【结 构 式】 |
【分子编号】66010 【品名】 【CA登记号】 |
【 分 子 式 】C16H27NO9 【 分 子 量 】377.39172 【元素组成】C 50.92% H 7.21% N 3.71% O 38.16% |
合成路线1
该中间体在本合成路线中的序号:(XXIII)The synthetic precursor (I) is obtained by ketalization of the α-methyl glycoside of N-acetylneuraminic acid methyl ester (XXII) with Me2C(OMe)2 in the presence of catalytic p-TsOH·H2O in acetone, followed by O-protection of the obtained 8,9-O-isopropylidene derivative (XXIII) with TBDMSCl by means of imidazole in DMF to yield the protected ether (XXIV) (3). Then, methylation of the remaining free C-7 alcohol group with Me2SO4 in the presence of NaH in DMF affords the corresponding methyl ether (XXV) (9). Treatment of either protected (XXV) (9) or unprotected (XXVI) acetamido triol (10) with Ac2O, AcOH and H2SO4 followed by ring opening of the resulting oxazoline with NaN3 in the presence of Dowex 50W provides azide (XXVII) (9, 10), which is then reduced to amine (I) by means of PPh3 (3) or H2 over Lindlar catalyst in EtOH (9, 10). Scheme 3.
【3】 Nakamura, Y., Murakami, M., Yamaoka, M., Wakayama, M., Umeo, K. (Daiichi Sankyo Co., Ltd.). Method for manufacturing neuraminic acid derivatives. EP 2132191, JP 2010523472, WO 2008126943. |
【9】 Anazawa, K., Furuhata, K., Ogura, H. Synthesis of 7-O-acetyl-n-acetylneuraminic acid derivative. Chem Pharm Bull 1988, 36(12): 4976. |
【10】 Honda, T., Masuda, T., Yoshida, S., Arai, M., Kaneko, S., Yamashita, M. Synthesis and anti-influenza virus activity of 7-O-alkylated derivatives related to zanamivir. Bioorg Med Chem Lett 2002, 12(15): 1925-8. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 65992 | C17H26N2O9 | 详情 | 详情 | ||
(XXII) | 66009 | 2-O-Methyl-beta-D-N-acetylneuraminic acid methyl ester | 6730-43-4 | C13H23NO9 | 详情 | 详情 |
(XXIII) | 66010 | C16H27NO9 | 详情 | 详情 | ||
(XXIV) | 66011 | C22H41NO9Si | 详情 | 详情 | ||
(XXV) | 66012 | C23H43NO9Si | 详情 | 详情 | ||
(XXVI) | 66013 | C13H23NO9 | 详情 | 详情 | ||
(XXVII) | 66014 | C17H24N4O9 | 详情 | 详情 |