DABSO-mediated Pummerer reaction enables one-pot synthesis of pyrroloquinolines for accessing marinoquinolines: mechanistic, photophysical and pharmacological investigations

Abstract

A new one-pot acid- and exogenous oxidant-free synthesis of pyrrolo[2,3-c]quinolines has been developed. This strategy involves the chemoselective reduction of 3-(2-nitrophenyl)-1H-pyrroles (pyrrolnitrin derivatives) followed by a DABSO-facilitated Pummerer reaction in the presence of diverse sulfoxides, which enables the formal [5 + 1] heteroannulation of the resultant 3-(2-aminophenyl)-1H-pyrroles (aminopyrrolnitrin derivatives) to give access to the 3H-pyrrolo[2,3-c]quinoline [3H-PQ] scaffold. The present strategy discloses the first example of an SO₂-facilitated Pummerer reaction and facilitates the synthesis of marinoquinoline natural products. Mechanistic investigation including computational studies have been conducted to decipher the underlying mechanism. Also, photophysical investigation of most of the synthesized compounds has been conducted. In addition, antimalarial activity screening revealed potent bioactivity in the micromolar range for some of the synthesized 3H-PQ derivatives.