著者
高木 泰 土屋 務 三宅 俊昭 竹内 富雄 梅澤 純夫
出版者
The Society of Synthetic Organic Chemistry, Japan
雑誌
有機合成化学協会誌 (ISSN:00379980)
巻号頁・発行日
vol.50, no.2, pp.131-142, 1992-02-01 (Released:2009-11-16)
参考文献数
41
被引用文献数
3 4

Anthracycline antibiotics, represented by daunorubicin and doxorubicin, are important antitumor agents widely used in clinical treatment. Their use is, however, restricted by the cardiotoxic character and other undesirable side-effects. To overcome these drawbacks and expand the utility, many efforts have been made for the past two decades. Recently we have synthesized a compound with strong antitumor activity and weak toxicity, 7-O- (2, 6-dideoxy-2-fluoro-α-L-talopyranosyl) adriamycinone, in which the glycosidic bond is comparatively stable in acid-catalyzed hydrolysis by the presence of highly electronegative fluorine atom at C-2'. This article describes the recent studies on the synthesis of the 2'-fluoroanthracycline antibiotics and their 14, 3', and 4'-substituted derivatives together with structure-activity relationship. It was found that R-configuration at C-2' having the fluorine is requisite to exhibit strong antitumor activity; thus (2'S) -fluoro and 2', 2'-difluoro analogs were devoid of activity. Synthesis of 2'-methoxyl analogs is also described.