Synthesis and Biological Evaluation of Quinaldopeptin

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• 作者：Katsushi Katayama ; Takuya Okamura ; Takuya Sunadome ; Koji Nakagawa ; Hiroshi Takeda ; Motoo Shiro ; Akira Matsuda ; Satoshi Ichikawa
• 刊名：Journal of Organic Chemistry
• 出版年：2014
• 出版时间：March 21, 2014
• 年：2014
• 卷：79
• 期：6
• 页码：2580-2590
• 全文大小：668K
• 年卷期：v.79,no.6(March 21, 2014)
• ISSN：1520-6904

文摘

The second-generation total synthesis of quinaldopeptin (1) was established via a Staudinger/aza-Wittig/diastereoselective Ugi three-component reaction sequence and a racemization-free [5 + 5] coupling and macrolactamization. A single-crystal X-ray structure of the chromophore analogue 26 confirmed the structural and stereochemical assignments of the macrocycle. Synthetic 1 successfully unwound supercoiled DNA to form a relaxed DNA in a dose-dependent manner, the binding affinity of 1 to four dsODNs was within a similar range (K_b = 1.45鈥?.53 脳 10⁷ M^鈥?), and the sequence selectivity was subtle. It was suggested that 1 possesses biological behaviors similar to those of sandramycin (2) in terms of cytotoxic activity against human cancer cell lines (IC₅₀ = 3.2鈥?2 nM) and HIF-1 inhibitory activity.