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.
