Gram Scale Synthesis of Membrane-Active Antibacterial 4-Quinolone Lead Compound

Abstract

An improved method for the synthesis of a new quinolone class of antibiotics, which are exceptionally potent against gram-positive bacteria, has been developed and the structure confirmed by single-crystal X-ray analysis. In the course of synthesis, using either Chan−Lam coupling or Buchwald−Hartwig amination, we have shown that the careful choice of protecting group at the C4 position of the quinoline is required for selective amination at the C5 position and subsequent deprotection to avoid the formation of a novel pyrido[4,3,2-de]quinazoline tetracycle.

Lewis Acid Catalyzed [4 + 2] Annulation of Propargylic Alcohols with 2-Vinylanilines

“…Quinoline derivatives, belonging to one of the most prominent and significantly important classes of nitrogen-containing heterocyclics, play an outstandingly vital role in both academic and industrial communities. , Indeed, quinoline derivatives as a prominent class of elaborated molecular architectures are distinctive and remain a hot spot because they are ubiquitous structural motifs in a wide array of agrochemicals, pharmaceuticals, and functional materials. , In particular, the efficient and practical strategy for the assembly of those target molecules has been the focus of a number of research initiatives because they could guarantee the fast identification of biologically and pharmacologically relevant natural products . Over the past few decades, continuous interest regarding the quinoline framework has been witnessed, which provided a greater diversity of quinoline derivatives for research .…”