Structural analogues of quinoline alkaloids: Straightforward route to [1,3]dioxolo[4,5-c]quinolines with antibacterial properties

Compounds bearing 1,3]dioxolo-quinoline scaffolds have been found in quinoline-based natural products; the only exception is the 1,3]dioxolo4,5-c]quinoline moiety with a rare occurrence in both natural and synthetic derivatives. In this article, we report the preparation of diversely substituted and functionalized 1,3]dioxolo4,5-c]quinolines using 1,3]dioxolo4,5-c]quinoline-4-carbaldehyde (DQC) as the common intermediate. DQC was synthesized on a large scale from anthranilic acid and chloroacetone as the starting materials, with the rearrangement of acetonyl-anthranilate as the key step. The developed method allows for the simple preparation of 1,3]dioxolo4,5-c]quinolines with various C2 substituents on the quinoline scaffold. Additionally, the synthetic route was successfully applied to the preparation of 3-hydroxyquinoline-4(1H)-ones. The target compounds were tested against representative Gram-positive/negative bacteria, and two derivatives exhibited submicromolar minimum inhibitory concentrations against Micrococcus luteus.