Synthesis and biological evaluation of Suffrutines A, B and their N-fused analogues
Abstract: A facile synthetic route to the natural products suffrutines A (1a), B (1b) and their N-fused analogues (2a, 2b) has been accomplished starting from pyrrole in 8 steps. Their structures were elucidated by a series of NMR spectra and the single-crystal X-ray crystallography. The in-situ 1HNMR monitoring experiments showed the interconversion properties of four suffrutines isomers and a stability order of 1a (E, E) > 1b (Z, E) > 1d (Z, Z) > 1c (E, Z) in solution state under ambient conditions. DFT calculations further clarified the tautomerization results. Preliminary biological tests showed that 1’-aza-suffrutines B (2b) was the most potent in cytotoxic study (MCF-7, IC50 = 7.13 μM), while 1’-aza-suffrutines A (2a) was most active in a 14-day colony formation assay. In addition, 2a was proved to be a cancer cell apoptosis inducer in annexin V-FITC/PI dual staining tests.