2、Semi-synthesis and biological evaluation of analogues of UK-2A.pdf

Bioorganic Medicinal Chemistry Letters 15 (2005) 2011–2014 Semi-synthesis and biological evaluation of analogues of UK-2A, a novel antifungal antibiotic from Streptomyces sp. 517-02 Yoshinosuke Usuki,a,* Koichi Mitomo,c Noriko Adachi,a Xu Ping,b Ken-Ichi Fujita,b Osamu Sakanaka,c Katsuharu Iinuma,d Hideo Iioa and Makoto Taniguchib,* aDepartment of Material Science, Graduate School of Science, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan bDepartment of Biology, Graduate School of Science, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan c CMC Research Laboratories, Meiji Seika Kaisha Ltd, Kayama, Odawara-shi, Kanagawa 250-0852, Japan dFuji Amide Chemical Co., Ltd, Ukima, Kita-ward, Tokyo 115-0051, Japan Received 17 January 2005; revised 17 February 2005; accepted 19 February 2005 Abstract—Several analogues of UK-2A, a novel antifungal antibiotic isolated from Streptomyces sp. 517-02, were semi-synthesized for structure–activity studies. In vitro antifungal activities of these compounds against Saccharomyces cerevisiae IFO 0203 were evalu- ated by the conventional paper disk method. Several derivatives exhibited growth inhibitory activity similar to UK-2A. 2005 Elsevier Ltd. All rights reserved. UK-2A is an antifungal antibiotic produced by Strepto- myces sp. 517-02, and is similar to antimycin A3 (AA) in both structure and inhibitory activity toward electron transport at complex III in mitochondria.1–4 Both UK- 2A and AA consist of nine-membered dilactone rings linked via an amide bond to an aromatic acid moiety (Fig. 1): UK-2A possesses a 3-hydroxy-4-methoxypicol- inic moiety, while the AAs have 3-formamidosalicylic moieties, reported to be essent