著者

池田 大四郎 味戸 慶一

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.49, no.11, pp.1002-1012, 1991-11-01 (Released:2009-11-16)

参考文献数

46

被引用文献数

2 3

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Anthracycline antibiotics, adriamycin, daunomycin and aclacinomycin A, have been widely used in the clinical treatment of various tumor diseases. Recently, semisynthetic anthracyclines, pirarubicin and epirubicin having improved antitumor effects and reduced adverse reactions in comparison with the parent compound, have been launched into clinical chemotherapy. Furthermore, several semisynthetic agents are under the clinical trials (phase I or phase II stage). In our search for useful and orally absorbable analogs, we synthesized a new barminomycin analog and a number of pirarubicin analogs. Barminomycins I and II have the unique eight-membered acetal-azomethine ring structure and show the strong activity in vitro. A new barminomycin analog (1) has been synthesized through the hypothetical biogenic intermediate, 4'-O-glycosyldaunomycin (22). The activity of 1 in vitro is stronger than that of the parent daunomycin. The quantitative structure-activity relationships of orally absorbable pirarubicin analogs are also discussed. The gastrointestinal absorption of salicylidene analogs of pirarubicin depends on the van der Waals volume of the substituent (s) on the salicylidene moiety and the polarity of the molecule.