Detection of Bacterial Neutral Ceramidase in Diabetic Foot Ulcers with an Optimized Substrate and Chemoenzymatic Probes.

Ceramidases (CDases) are important in controlling skin barrier integrity by regulating ceramide composition and affording downstream signal molecules. While the functions of epidermal CDases are known, roles of neutral CDases secreted by skin-residing microbes are undefined. Here, we developed a one-step fluorogenic substrate, S-B, for specific detection of bacterial CDase activity and inhibitor screening. We identified a non-hydrolyzable substrate mimic, C6, as the best hit. Based on C6, we designed a photoaffinity probe, JX-1, which efficiently detects bacterial CDases. Using JX-1, we identified endogenous low-abundance PaCDase in a P. aeruginosa monoculture and in a mixed skin bacteria culture. Harnessing both S-B and JX-1, we found that CDase activity positively correlates with the relative abundance of P. aeruginosa and is negatively associated with wound area reduction in clinical diabetic foot ulcer patient samples. Overall, our study demonstrates that bacterial CDases are important regulators of skin ceramides and potentially play a role in wound healing.

Brønsted Base-Switched Selective Mono- and Dithiolation of Benzamides via Copper Catalysis.

A versatile protocol for the direct thiolation of an inert sp2 C-H bond is presented via a catalytic amount of copper catalysis, by switching related Brønsted bases and regulating the reaction time, and the corresponding mono- and dithiolation products can be obtained selectively in moderate to good yields. The reaction exhibits a relatively broad substrate scope and a good functional group tolerance, even with different heterocyclic amides and alkyl thiols.

Synthesis of α-arylthioacetones using TEMPO as the C3 synthon via a reaction cascade of sequential oxidation, skeletal rearrangement and C-S bond formation.

Here, we present an unprecedented pathway to α-sulfenylated carbonyl compounds from commercially available thiols and universally employed TEMPO and its analogues, which act as C3 synthons through skeletal rearrangement under simple and metal-free conditions. Mechanism studies suggest that this reaction involves a consecutive radical oxidation and cation coupling process. TEMPO analogues and thiols serve as oxidants and reductive reagents, respectively, along the radical process, while in the coupling process, the former ones afford C3 synthons to couple with related sulfur sources.

KI-catalyzed C-S bond formation via an oxidation relay strategy: efficient access to various α-thio-ß-dicarbonyl compounds.

An efficient and practical methodology to obtain α-thio-ß-dicarbonyl compounds was presented under alkaline conditions via potassium iodide (KI) catalysis; various symmetrical/unsymmetrical 1,3-dicarbonyl compounds were obtained under an aerobic atmosphere in moderate to excellent yields, with good functional group tolerance. Notably, a widely used anti-inflammatory drug butazodine could be modified with our protocol, even on a gram scale.

Direct access to α-sulfenylated amides/esters via sequential oxidative sulfenylation and C-C bond cleavage of 3-oxobutyric amides/esters.

An efficient, environmentally benign and unprecedented synthesis of various α-sulfenylated amides/esters has been developed under oxygen atmosphere. The reaction shows good functional group tolerance and excellent chemo/regioselectivity. All the desired products were obtained in moderate to excellent yields, even on the gram scale. Practically, the related α-thiol Weinreb amide can be readily transferred to a series of prospective compounds, and selenium atom can be introduced to the α-sites of the amides in high yields.