1. Total Synthesis of 6-Deoxypladienolide D and Assessment of Splicing Inhibitory Activity in a Mutant SF3B1 Cancer Cell Line
- Author
-
Huiming Zhang, Linda Lee, Sudeep Prajapati, Betty Chan, Kazunobu Kira, Mingde Shan, Laura Corson, Ming-Hong Hao, Kuo-Ming Wu, O'shea Morgan Welzel, Yoshiharu Mizui, Samantha Perino, John Wang, Eun Sun Park, Lisa A. Marcaurelle, Marta Nevalainen, Arai Kenzo, Guo-Zhu Zheng, Markus Warmuth, Lihua Yu, Atsushi Endo, Jason T. Lowe, Xiang Liu, Baudouin Gerard, Pete Smith, Tivitmahaisoon Parcharee, Craig Karr, Silvia Buonamici, Keaney Gregg F, and Tuoping Luo more...
- Subjects
RNA Splicing Factors ,Stereochemistry ,RNA Splicing ,Mutant ,Antineoplastic Agents ,Biochemistry ,chemistry.chemical_compound ,Cell Line, Tumor ,Humans ,Physical and Theoretical Chemistry ,Cell Proliferation ,Binding Sites ,Natural product ,Drug discovery ,Cell growth ,Organic Chemistry ,Total synthesis ,Ribonucleoprotein, U2 Small Nuclear ,Phosphoproteins ,chemistry ,RNA splicing ,Epoxy Compounds ,Macrolides ,Growth inhibition - Abstract
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. more...
- Published
- 2014
- Full Text
- View/download PDF