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

(+)-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 EC 50 value equal to 0.85 μM. It also inhibited the cell proliferation and colony formation of the K562 human leukemia cell line.