Total Synthesis of 6-Deoxypladienolide D and Assessment of Splicing Inhibitory Activity in a Mutant SF3B1 Cancer Cell Line

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• 作者：Kenzo Arai ; Silvia Buonamici ; Betty Chan ; Laura Corson ; Atsushi Endo ; Baudouin Gerard ; Ming-Hong Hao ; Craig Karr ; Kazunobu Kira ; Linda Lee ; Xiang Liu ; Jason T. Lowe ; Tuoping Luo ; Lisa A. Marcaurelle ; Yoshiharu Mizui ; Marta Nevalainen ; Morgan Welzel O鈥橲hea ; Eun Sun Park ; Samantha A. Perino ; Sudeep Prajapati ; Mingde Shan ; Peter G. Smith ; Parcharee Tivitmahaisoon ; John Yuan Wang ; Markus Warmuth ; Kuo-Ming Wu ; Lihua Yu ; Huiming Zhang ; Guo-Zhu Zheng ; Gregg F. Keaney
• 刊名：Organic Letters
• 出版年：2014
• 出版时间：November 7, 2014
• 年：2014
• 卷：16
• 期：21
• 页码：5560-5563
• 全文大小：343K
• ISSN：1523-7052

文摘

A total synthesis of the natural product 6-deoxypladienolide D (1) has been achieved. Two noteworthy attributes of the synthesis are (1) a late-stage allylic oxidation which proceeds with full chemo-, regio-, and diastereoselectivity and (2) the development of a scalable and cost-effective synthetic route to support drug discovery efforts. 6-Deoxypladienolide D (1) demonstrates potent growth inhibition in a mutant SF3B1 cancer cell line, high binding affinity to the SF3b complex, and inhibition of pre-mRNA splicing.