Divergent synthesis of prenylated carbazole alkaloid (+)-S-mahanimbine led to the discovery of a notch activator

By Nalli Yedukondalu, Gourav Gupta, Janhavi R.Nadkarni, Vivek Kumar Gupta, Sajad Hussain Syed, Asif Ali

July 28, 2017

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Title

Divergent synthesis of prenylated carbazole alkaloid (+)-S-mahanimbine led to the discovery of a notch activator

Author

Nalli Yedukondalu, Gourav Gupta, Janhavi R.Nadkarni, Vivek Kumar Gupta, Sajad Hussain Syed, Asif Ali

Year

2016

Journal

RSC Advances

Abstract

(+)-Mahanimbine (1), a prenylated carbazole alkaloid, was isolated from the stems of Murraya koenigii. Herein we developed a divergent synthesis by the Vilsmeier–Haack reaction, which involves unusual oxidative cyclization and transformation to several distinct tetracyclic carbazole natural products (2–9). The new chemical entities were identified by extensive 1D and 2D NMR data, HR-ESI-MS, and comparison with the known literature. Compounds 2 and 5 were further characterized by X-ray crystal analysis. Compounds (1–9) were screened against the notch pathway activation in which the new compound 8 exhibited prominent notch activation in a reporter gene assay with an EC50 value equal to 0.85 μM. It also inhibited the cell proliferation and colony formation of the K562 human leukemia cell line.

Full Article

http://pubs.rsc.org/en/content/articlelanding/2016/ra/c6ra16531a

Instrument

J-810

Keywords

Circular dichroism, Absolute configuration, Natural products