TY - JOUR
T1 - Synthetic Studies on Selective, Proapoptotic Isomalabaricane Triterpenoids Aided by Computational Techniques
AU - Boyko, Yaroslav D.
AU - Huck, Christopher J.
AU - Ning, Shang
AU - Shved, Alexander S.
AU - Yang, Cheng
AU - Chu, Tiffany
AU - Tonogai, Emily J.
AU - Hergenrother, Paul J.
AU - Sarlah, David
N1 - Funding Information:
Financial support for this work was provided by the University of Illinois (Seemon H. Pines Graduate Fellowship to Y.B.), Bristol-Myers Squibb (predoctoral fellowship to Y.B.), the National Science Foundation (predoctoral fellowship to C.J.H), and Robert C. and Carolyn J. Springborn (predoctoral fellowship to C.J.H). Bristol-Myers Squibb, Amgen, Eli Lilly, and FMC are also acknowledged for unrestricted research support. The Bruker 500-MHz NMR spectrometer was obtained with the financial support of the Roy J. Carver Charitable Trust, Muscatine, Iowa, USA. We also thank Dr. D. Olson and Dr. L. Zhu for NMR spectroscopic assistance, Dr. D. L. Gray and Dr. T. Woods for X-ray crystallographic analysis assistance, and F. Sun for mass spectrometric assistance. We thank Connor Delaney and Prof. Scott Denmark for helpful discussions regarding the Suzuki coupling. We acknowledge Marko Nesic, Lorenzo Estrada, and Fyodor Kryshchenko for technical assistance. Finally, we would like to thank Aaron Zhong and Prof. Paul Chirik for a generous gift of the [Co(dppb)(CHTMS)] catalyst. 2 2
Publisher Copyright:
© 2021 American Chemical Society.
PY - 2021/2/3
Y1 - 2021/2/3
N2 - The isomalabaricanes comprise a large family of marine triterpenoids with fascinating structures that have been shown to be selective and potent apoptosis inducers in certain cancer cell lines. In this article, we describe the successful total syntheses of the isomalabaricanes stelletin A, stelletin E, and rhabdastrellic acid A, as well as the development of a general strategy to access other natural products within this unique family. High-throughput experimentation and computational chemistry methods were used in this endeavor. A preliminary structure-activity relationship study of stelletin A revealed the trans-syn-trans core motif of the isomalabaricanes to be critical for their cytotoxic activity.
AB - The isomalabaricanes comprise a large family of marine triterpenoids with fascinating structures that have been shown to be selective and potent apoptosis inducers in certain cancer cell lines. In this article, we describe the successful total syntheses of the isomalabaricanes stelletin A, stelletin E, and rhabdastrellic acid A, as well as the development of a general strategy to access other natural products within this unique family. High-throughput experimentation and computational chemistry methods were used in this endeavor. A preliminary structure-activity relationship study of stelletin A revealed the trans-syn-trans core motif of the isomalabaricanes to be critical for their cytotoxic activity.
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U2 - 10.1021/jacs.0c12569
DO - 10.1021/jacs.0c12569
M3 - Article
C2 - 33464048
AN - SCOPUS:85100316003
SN - 0002-7863
VL - 143
SP - 2138
EP - 2155
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 4
ER -