Efficient total synthesis of neocryptolepine and synthetic access to 6-methylquinindoline from a common intermediate. Issue 45 (30th May 2017)

• Record Type: Journal Article
• Authors: Méndez, María V.; Heredia, Daniel A.; Larghi, Enrique L.; Bracca, Andrea B. J.; Kaufman, Teodoro S.
• Is Part Of: RSC advances. Volume 7:Issue 45(2017)
• Page Start: 28298
• Page End: 28307
• Publication Date: 2017-05-30
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c7ra05349e
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : 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. Abstract : 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 K2 CO3 -assisted cyclization to form a 3-(2-nitrophenyl)quinolin-2-one as the common precursor. Me2 CO3 -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 POCl3 -promoted C–N bond forming reactions, two Fe-mediated nitro group reductions and two base-promoted transformations.