在C-3'或C-4'位修饰的7-O-(2,6-二脱氧-2-氟-α-L-塔罗吡喃糖基)柔红霉素酮衍生物的合成及其抗肿瘤活性

Synthesis and antitumor activity of 7-O-(2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl) daunomycinone derivatives modified at C-3' or C-4'.

作者信息

Takagi Y, Kobayashi N, Chang M S, Lim G J, Tsuchiya T

机构信息

Institute of Bioorganic Chemistry, Kawasaki, Japan.

出版信息

Carbohydr Res. 1998 Feb;307(3-4):217-32. doi: 10.1016/s0008-6215(98)00026-3.

DOI:10.1016/s0008-6215(98)00026-3

PMID:9675364

Abstract

As a part of a study to exploit anthracycline glycosides effective against resistant tumor cells, the 3'-O-methyl (3), 4'-O-methyl (4), 3'-deoxy (6), 3'-deoxy-3'-fluoro (7), and 3'-deoxy-3'-iodo (8) derivatives of 7-O-(2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl)daunomycinone have been prepared by coupling suitably protected glycosyl bromides with daunomycinone. The doxorubicin-type analog (5) of 4 was also prepared. Among the compounds prepared, 5 showed the highest antitumor activity. Relationships between chemical structures of the synthetic products and antitumor activities, together with the degree of resistance were discussed.

摘要

作为一项开发对耐药肿瘤细胞有效的蒽环类糖苷研究的一部分，通过将适当保护的糖基溴化物与柔红霉素酮偶联，制备了7-O-(2,6-二脱氧-2-氟-α-L-塔罗吡喃糖基)柔红霉素酮的3'-O-甲基(3)、4'-O-甲基(4)、3'-脱氧(6)、3'-脱氧-3'-氟(7)和3'-脱氧-3'-碘(8)衍生物。还制备了4的阿霉素型类似物(5)。在所制备的化合物中，5显示出最高的抗肿瘤活性。讨论了合成产物的化学结构与抗肿瘤活性之间的关系以及耐药程度。