7-O-[2,6-二脱氧-2-氟-5-C-(三氟甲基)-α-L-塔罗吡喃糖基]-柔红霉素酮和-阿霉素酮的合成及其抗肿瘤活性

Synthesis and antitumor activity of 7-O-[2,6-dideoxy-2-fluoro-5-C-(trifluoromethyl)-alpha-L-talopyranosyl]- daunomycinone and -adriamycinone.

作者信息

Nakai K, Takagi Y, Tsuchiya T

机构信息

Institute of Bioorganic Chemistry, Kawasaki, Japan.

出版信息

Carbohydr Res. 1999 Mar 31;316(1-4):47-57. doi: 10.1016/s0008-6215(99)00028-2.

DOI:10.1016/s0008-6215(99)00028-2

PMID:10420587

Abstract

7-O-[2,6-Dideoxy-2-fluoro-5-C-(trifluoromethyl)-alpha-L-talopyranosyl]- daunomycinone and -adriamycinone have been prepared by the coupling of 3,4-di-O-acetyl-2,6-dideoxy-2-fluoro-5-C-(trifluoromethyl)-alpha-L- talopyranosyl iodide with daunomycinone. The key steps in this synthesis are the regioselective fluorination of methyl alpha-D-lyxopyranoside to give the 4-deoxy-4-fluoro-beta-L-ribopyranoside and the C-trifluoromethylation of the aldehydo-L-ribose derivative to give the 1,1,1-trifluoro-5-monofluoro-L-altritol derivative. Antitumor activities of the synthetic products were compared with those for the 2'-deoxy-2'-fluoro and 2',6'-dideoxy-5'-C-trifluoromethyl analogs.

摘要

通过将3,4-二-O-乙酰基-2,6-二脱氧-2-氟-5-C-(三氟甲基)-α-L-塔罗吡喃糖基碘与柔红霉素酮偶联，制备了7-O-[2,6-二脱氧-2-氟-5-C-(三氟甲基)-α-L-塔罗吡喃糖基]-柔红霉素酮和-阿霉素酮。该合成中的关键步骤是α-D-来苏糖吡喃糖苷的区域选择性氟化以得到4-脱氧-4-氟-β-L-核糖吡喃糖苷，以及醛基-L-核糖衍生物的C-三氟甲基化以得到1,1,1-三氟-5-单氟-L-阿卓糖醇衍生物。将合成产物的抗肿瘤活性与2'-脱氧-2'-氟和2',6'-二脱氧-5'-C-三氟甲基类似物的抗肿瘤活性进行了比较。