A facile access to 2-substituted naphtho[2,3-g]quinoline-3-carboxylic acid esters via intramolecular cyclization and PyBOP-promoted functionalization

Abstract

Heteroarene-fused derivatives of anthraquinone (anthracene-9,10-dione) represent an exceptionally productive class for the search for new anticancer compounds with improved properties. In this study, we report a convenient heterocyclization, which in three steps leads to 2-alkyl-, aryl-, or hydroxyl derivatives of 5,12-dimethoxynaphtho[2,3-g]quinoline-3-carboxylic acid esters. The scheme includes an alkylation of CH-acids with 2-(bromomethyl)-1,4-dimethoxy-3-nitroanthraquinone (8) followed by reductive cyclization and oxidative aromatization. To increase the series of naphtho[2,3-g]quinoline derivatives, a mild and effective PyBOP-mediated functionalization was developed, which introduced N-, S-, and O-nucleophiles at the 2-position of the quinoline core. We believe that this study allows to access a broad family of 2-substituted naphtho[2,3-g]quinolines and can be adapted for other quinoline derivatives or polyaromatic analogs.