Efficient total synthesis of neocryptolepine and synthetic access to 6-methylquinindoline from a common intermediateElectronic supplementary information (ESI) available: Selected spectra of intermediates and final product. See DOI: 10.1039/c7ra05349e

• Main Authors: Méndez, María V, Heredia, Daniel A, Larghi, Enrique L, Bracca, Andrea B. J, Kaufman, Teodoro S
• Format: Journal Article
• Language: English
• Published: 30.05.2017
• ISSN: 2046-2069
• DOI: 10.1039/c7ra05349e

A convenient approach toward the indoloquinolines neocryptolepine and 6-methylquinindoline from a common intermediate, is reported. Both sequences, designed for maximum use of accessible reagents and robust conditions, are straightforward and efficient. They involved the amidation of 2-aminobenzaldehyde (prepared by iron-mediated reduction of 2-nitrobenzaldehyde) with 2-nitrophenylacetic acid, followed by a K 2 CO 3 -assisted cyclization to form a 3-(2-nitrophenyl)quinolin-2-one as the common precursor. Me 2 CO 3 -mediated N -methylation of the lactam, reduction of the nitro moiety and final cyclization resulted in 55% overall yield of neocryptolepine, whereas cyclocondensation and N -methylation afforded 79% overall yield of 6-methyl quinindoline. Thus, the sequences toward the targets entailed two POCl 3 -promoted C-N bond forming reactions, two Fe-mediated nitro group reductions and two base-promoted transformations. The total synthesis of neocryptolepine and the synthesis of its non-natural isomer 6-methyl quinindoline were efficiently achieved in a few steps from a common intermediate.