Development of 2nd generation aminomethyl spectinomycins that overcome native efflux in abscessus.

(), a nontuberculous mycobacterial (NTM) species, is an emerging pathogen with high intrinsic drug resistance. Current standard-of-care therapy results in poor outcomes, demonstrating the urgent need to develop effective antimycobacterial regimens. Through synthetic modification of spectinomycin (SPC), we have identified a distinct structural subclass of N-ethylene linked aminomethyl SPCs (eAmSPCs) that are up to 64-fold more potent against over the parent SPC.

Targeting Helicobacter pylori for antibacterial drug discovery with novel therapeutics.

Helicobacter pylori is an important human pathogen with increasing antimicrobial resistance to standard-of-care antibiotics. Treatment generally includes a combination of classical broad-spectrum antibiotics and a proton-pump inhibitor, which often leads to perturbation of the gut microbiome and the potential for the development of antibiotic resistance. In this review, we examine reports, primarily from the past decade, on the discovery of new anti-H.

Solvent Effects and Mechanistic Studies for ReO-Catalyzed Allylative Annulation Reactions.

The sequence of allylic alcohol transposition, carbonyl group trapping, oxocarbenium ion formation, and nucleophilic addition results in the formation of a ring while serving as a fragment-coupling and stereocenter-generating reaction. Successful applications of these processes require a balancing of the kinetics of numerous productive and unproductive steps. This work describes the manner in which solvent changes can be used to expand the scope and change the stereochemical outcomes of these processes.

Condensation reactions of guanidines with bis-electrophiles: Formation of highly nitrogenous heterocycles.

2-Amino-1,4-dihydropyrimidines were reacted with bis-electrophiles to produce novel fused bi-pyrimidine, pyrimido-aminotriazine, and pyrimido-sulfonamide scaffolds. In addition, a quinazoline library was constructed using a guanidine Atwal-Biginelli reaction with 1-(quinazolin-2-yl)guanidines. The product heterocycles have novel constitutions with high nitrogen atom counts and represent valuable additions to screening libraries for the discovery of new modulators of biological targets.