Stephen M. Geddis

Propionate is an abundant catabolite in nature and represents a rich potential source of carbon for the organisms that can utilize it. However, propionate and propionate-derived catabolites are also toxic to cells, so propionate catabolism can alternatively be viewed as a detoxification mechanism. In this review, we summarize recent progress made in understanding how prokaryotes catabolize propionic acid, how these pathways are regulated and how they might be exploited to develop novel antibacterial interventions.

Abstract The synthesis of four quinolone natural products from the actinomycete Pseudonocardia sp. is reported. The key step involved a sp 2 –sp 3 Suzuki–Miyaura reaction between a common boronic ester lateral chain and various functionalised quinolone cores. The quinolones slowed growth of E. coli and S. aureus by inducing extended lag phases.

The advancement of an effective hydrogen liberation technology from liquid organic hydrogen carriers, particularly cycloalkanes such as cyclohexane and methylcyclohexane, holds significance in realizing a hydrogen-centric society. However, the attainment of homogeneous catalytic acceptorless dehydrogenation characterized by elevated selectivity for thorough aromatization under mild conditions remains unrealized. In this study, a catalyst system, facilitated by a double hydrogen atom transfer processes, has been devised for the catalytic acceptorless dehydrogenation of inert cycloalkanes at ambient temperature under visible light irradiation. Through the synergistic utilization of tetrabutylammonium chloride and thiophosphoric acid hydrogen atom transfer catalysts, successful catalytic acceptorless dehydrogenation with comprehensive aromatization has been accomplished with potential liquid organic hydrogen carrier candidates and showcased high functional group tolerance. The development of hydrogen atom transfer (HAT) in homogeneous catalytic acceptorless dehydrogenation (CAD) with selectivity for thorough aromatization under mild conditions remains challenging. Here, the authors propose a catalyst system that facilitates a double hydrogen atom transfer (HAT) processes for the CAD of inert cycloalkanes at ambient temperature under visible light irradiation.

Two divergent synthetic routes are reported offering access to four quinolone natural products from Pseudonocardia sp. CL38489. Key steps to the natural products involved a regioselective epoxidation, an intramolecular Buchwald–Hartwig amination and a final acid‐catalysed 1,3‐allylic‐alcohol rearrangement to give two of the natural products in one step. This study completes the synthesis of all eight antibacterial quinolone natural products reported in the family. In addition, this modular strategy enables an improved synthesis towards two natural products previously reported.

A series of analogues of Pseudonocardia sp. natural products were synthesized, which have been reported to possess potent antibacterial activity against Helicobacter pylori and induce growth defects in Escherichia coli and Staphylococcus aureus . Taking inspiration from a methodology used in our total synthesis of natural products, we applied this methodology to access analogues possessing bulky N-substituents, traditionally considered to be challenging scaffolds. Screening of the library provided valuable insights into the structure–activity relationship of the bacterial growth defects, and suggested that selectivity between bacterial species should be attainable. Furthermore, a structurally related series of analogues was observed to inhibit production of the virulence factor pyocyanin in the human pathogen Pseudomonas aeruginosa , which may be a result of their similarity to the Pseudomonas quinolone signal (PQS) quorum sensing autoinducer. This provided new insights regarding the effect of N-substitution in PQS analogues, which has been hitherto underexplored.