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

被引：19

作者：

Arai, Kenzo ^{[1
]}

Buonamici, Silvia ^{[1
]}

Chan, Betty ^{[1
]}

Corson, Laura ^{[1
]}

Endo, Atsushi ^{[2
]}

Gerard, Baudouin ^{[1
]}

Hao, Ming-Hong ^{[1
]}

Karr, Craig ^{[1
]}

Kira, Kazunobu ^{[1
]}

Lee, Linda ^{[1
]}

Liu, Xiang ^{[1
]}

Lowe, Jason T. ^{[1
]}

Luo, Tuoping ^{[1
]}

Marcaurelle, Lisa A. ^{[1
]}

Mizui, Yoshiharu ^{[1
]}

Nevalainen, Marta ^{[1
]}

O'Shea, Morgan Welzel ^{[1
]}

Park, Eun Sun ^{[1
]}

Perino, Samantha A. ^{[1
]}

Prajapati, Sudeep ^{[1
]}

Shan, Mingde ^{[2
]}

Smith, Peter G. ^{[1
]}

Tivitmahaisoon, Parcharee ^{[1
]}

Wang, John Yuan ^{[1
]}

Warmuth, Markus ^{[1
]}

Wu, Kuo-Ming ^{[2
]}

Yu, Lihua ^{[1
]}

Zhang, Huiming ^{[2
]}

Zheng, Guo-Zhu ^{[1
]}

Keaney, Gregg F. ^{[1
]}

机构：

[1] H3 Biomed Inc, Cambridge, MA 02139 USA

[2] Eisai Inc, Andover, MA 01810 USA

来源：

ORGANIC LETTERS | 2014年 / 16卷 / 21期

关键词：

PLADIENOLIDE-B; ANTITUMOR MACROLIDE; MUTATIONS; SUBSTANCES; CULTURE; ANALOG; TARGET; CORE; GENE;

D O I：

10.1021/ol502556c

中图分类号：

O62 [有机化学];

学科分类号：

070303 [有机化学];

摘要：

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.

引用

页码：5560 / 5563

页数：4

共 53 条

[1]

The anti-selective boron-mediated asymmetric aldol reaction of carboxylic esters [J].