N‐Acylethanolamine acid amidase (NAAA) is a cysteine amidase that preferentially hydrolyzes saturated or monounsaturated fatty acid ethanolamides (FAEs), such as palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), which are endogenous agonists of nuclear peroxisome proliferator‐activated receptor‐α (PPAR‐α). Compounds that feature an α‐amino‐β‐lactone ring have been identified as potent and selective NAAA inhibitors and have been shown to exert marked anti‐inflammatory effects that are mediated through FAE‐dependent activation of PPAR‐α. We synthesized and tested a series of racemic, diastereomerically pure β‐substituted α‐amino‐β‐lactones, as either carbamate or amide derivatives, investigating the structure–activity and structure–stability relationships (SAR and SSR) following changes in β‐substituent size, relative stereochemistry at the α‐ and β‐positions, and α‐amino functionality. Substituted carbamate derivatives emerged as more active and stable than amide analogues, with the cis configuration being generally preferred for stability. Increased steric bulk at the β‐position negatively affected NAAA inhibitory potency, while improving both chemical and plasma stability.

N-(2-Oxo-3-oxetanyl)carbamic acid esters have recently been reported to be noncompetitive inhibitors of the Nacylethanolamine acid amidase (NAAA) potentially useful for the treatment of pain and inflammation. In the present study, we further explored the structure−activity relationships of the carbamic acid ester side chain of 2-methyl-4-oxo-3-oxetanylcarbamic acid ester derivatives. Additional favorable features in the design of potent NAAA inhibitors have been found together with the identification of a single digit nanomolar inhibitor. In addition, we devised a 3D QSAR using the atomic property field method. The model turned out to be able to account for the structural variability and was prospectively validated by designing, synthesizing, and testing novel inhibitors. The fairly good agreement between predictions and experimental potency values points to this 3D QSAR model as the first example of quantitative structure−activity relationships in the field of NAAA inhibitors.

A divergent synthesis to eight d‐xylo‐ and l‐arabino‐cyclophellitol and cyclophellitol aziridine derivatives is described. The syntheses start from d‐xylose and feature asymmetric allylation followed by ring‐closing metathesis as key steps. Reaction of the cyclohexenes with methyl(trifluoromethyl)dioxirane yielded the title epoxides. The aziridines were prepared either from the epimeric epoxides or by direct aziridination of the cyclohexenes. Finally, beta‐xylosylation of 2,3‐di‐O‐benzyl‐xylo‐cyclophellitol yielded the corresponding cyclitol epoxide disaccharide, thereby expanding the utility of our strategy to the synthesis of potential endoglycosidase inhibitors.

A mild, inexpensive and general photocatalytic initiation protocol for anti-Markovnikov hydrothiolation of olefins using carbon nanomaterial/metal oxide (Carbon NM-MO) composites is reported. Graphene oxide (GO), nanodiamonds (ND) and carbon nano-onions (CNO) displaying bismuth or tungsten oxide nanoparticles adhered to the surface, function as highly efficient photocatalysts for thiol-ene ligation under both UV and visible-light-mediated The Supporting Information is available free of charge on the ACS Publications website at DOI:xxxxx Experimental procedures for nanocomposites preparation, Bright-field TEM of Bi 2 O 3-ox-CNO/GO nanocomposites, XPS of Bi 2 O 3 , 1 Hand 13 C-NMR Spectra of thioether and thioester products.

Cyclophellitol and cyclophellitol-aziridine are potent, mechanism-based and irreversible retaining -glucosidase inhibitors. We have become interested in these configurationalglucoside analogues as they proved to be a highly suitable starting point for the development of activity-based glycosidase probes. In this review, we provide an overview of the cyclophellitol-aziridine synthesis reported in the literature. Two con-