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

Abstract

Compounds bearing [1,3]dioxolo‐quinoline scaffolds have been found in quinoline‐based natural products; the only exception is the [1,3]dioxolo[4,5‐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]dioxolo[4,5‐c]quinolines using [1,3]dioxolo[4,5‐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]dioxolo[4,5‐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.

Recent Advances in the Synthesis of Fused Heterocyclic Compounds and Their Antitumor Activities

“…喹啉类化合物具有优良的药理活性, 在医药化学、 农药等领域应用广泛 [66][67][68] . 例如, 依伐卡托 211 作为一 种囊性纤维化跨膜传到调节剂增强剂, 可以用于治疗对 药物有反应特定基因突变的人囊性纤维化; 吡维胺 212 具有杀蛲虫作用, 是治疗蛲虫病的首选药; 非那沙星 213 作为一种氟喹诺酮类抗生素, 可以用于治疗由 2018 年, 江焕峰课题组 [71] 报道了一种锌催化叠氮 乙烯与芳基苯胺生成 4-取代喹啉的反应(Scheme 39).…”

Convenient Synthesis of Furo[3,2-b]quinolin-4(1H)-ones

“…As previously reported, derivative 1 can be easily synthesized in few steps starting from anthranilic acid and chloroacetone, and its synthesis can even be scaled up to multigram quantities. 18 Dioxoloquinoline 1 was subjected to reaction with diverse aryl bromides or iodides under Sonogashira cross-coupling conditions. Although this type of reaction was previously reported with both halogenated quinolines 19 or alkynylquinolines 20,21 as the starting materials, a screening of suitable reaction conditions was necessary to receive desired outcomes.…”

“…Although some limitation was detected in the cyclization step, the method allows the synthesis of variously C3-arylated furoquinolines. Additionally, modification of the benzene ring can be feasible as the substituted intermediates 1 can be simply synthesized using previously reported protocols 18 applied to different anthranilic acids. Overall, the strategy is applicable for the preparation of pharmacologically promising furoquinolines suitable for further research in the field of medicinal chemistry.…”

Ru(II)-Catalyzed Chemoselective C(sp3)–H Monoarylation of 8-Methyl Quinolines with Arylboronic Acids

“…Over the years, quinoline has gained significant attention of the researchers as it is the most versatile and important N -based heterocyclic compound found in the nature, particularly in alkaloids . Quinoline scaffolds are used as “parental moieties”, which are integrated into functionalized molecules with a wide range of applications in agrochemicals, pharmaceuticals, , and ligands in transition-metal catalysis . Owing to the importance of quinolines, various methods have been developed for their functionalization mainly using the Pd catalyst, but necessity of preactivated substrates, strong bases, and a stoichiometric amount of metal catalysts remained the main shortcomings .…”