最近の当研究室におけるアンスラサイクリン系抗生物質誘導体の合成

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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-<I>O</I>- (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<I>S</I>) -fluoro and 2, 2-difluoro analogs were devoid of activity. Synthesis of 2-methoxyl analogs is also described.
社団法人有機合成化学協会の論文