%0 Journal Article
%T Chemistry of Nitroquinolones and Synthetic Application to Unnatural 1-Methyl-2-quinolone Derivatives
%A Nagatoshi Nishiwaki
%J Molecules
%D 2010
%I MDPI AG
%R 10.3390/molecules15085174
%X The 1-methyl-2-quinolone (MeQone) framework is often found in alkaloids£¿and recently attention was drawn to unnatural MeQone derivatives with the aim of finding new biologically active compounds,£¿however, low reactivity of the MeQone framework prevents the syntheses of versatile derivatives. A nitro group is one of the useful activating groups for this framework that enables a concise chemical transformation. Among nitroquinolones, 1-methyl-3,6,8-trinitro-2-quinolone (TNQ) exhibits unusual reactivity favoring region-selective cine-substitutions that afford 4-substituted 1-methyl-6,8-dinitro-2-quinolones upon treatment with nucleophilic reagents. Contrary to this, 1-methyl-3,6-dinitro-2-quinolone (3,6-DNQ) does not undergo any reaction under the same conditions. The unusual reactivity of TNQ is caused by steric repulsion between the methyl group at the 1-position and the nitro group at the 8-position, which distorts the MeQone framework. As a result, the pyridone ring of TNQ loses aromaticity and acts rather as an activated nitroalkene. Indeed, the pyridone moiety of TNQ undergoes cycloaddition with electron-rich alkenes or dienes under mild conditions, whereby a new fused ring is constructed on the [c]-face of the MeQone. Consequently, TNQ can be used as a new scaffold leading to versatile unnatural MeQone derivatives.
%K unnatural 1-methyl-2-quinolone
%K cine-substitution
%K regioselective C-C bond formation
%K nitroalkene
%K cycloaddition
%U http://www.mdpi.com/1420-3049/15/8/5174