Structural influence of indole C5-N-substitutents on the cytotoxicity of seco-duocarmycin analogs

Abstract

A series of racemic indole C5-substituted seco-cyclopropylindoline compounds (2,3 and 5-7) were prepared by coupling 1-(tert-butyloxycarbonyl)-3-(chlorocarbonyl)indoline (seg-A) with 5,6,7-trimethoxy-, 5,6-dimethoxy-, 5-amino-, 5-methylsulfonylamino- and 5-(N,N-dimethylaminosulfonylamino) indole-2-carboxylic acid as seg-B in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide. The synthetic compounds (2,3 and 5-7) were tested for cytotoxic activity against human cancer cell lines (COLO 205, SK-MEL-2, A549, and JEG-3) using the MTT assay.

Carboxylic Acid-Promoted Single-Step Indole Construction from Simple Anilines and Ketones via Aerobic Cross-Dehydrogenative Coupling

“…Compound 3qa: light yellow solid; 1 H NMR (400 MHz, chloroform-d) δ 9.48 (br s, 1H), 8.38−8.35 (m, 1H), 7.99 (dd, J = 8.8, 1.7, 1H), 7.47 (d, J = 8.8, 1H), 7.33 (dd, J = 2.0, 0.9, 1H), 4.45 (q, J = 7.1, 2H), 2.67 (s, 3H), 1.44 (t, J = 7.1, 3H); 13 Methyl 5-(Methylsulfonamido)-1H-indole-2-carboxylate (3mh). 82 The compound was obtained by the following procedure: 1m (1.86 g, 10 mmol), Pd(OAc) 2 (0.22 g, 1 mmol), and 4 Å MS (1.0 g) were added to a 250 mL round-bottom flask equipped with a magnetic stirrer bar. After the air was evacuated and the flask was refilled with O 2 for three times, 2h (2.04 g, 20 mmol), AcOH (0.60 g, 10 mmol), and DMSO (100 mL) were added via syringe.…”