We report the first biological evaluation the 1,2,3-thiaselenazole class of compound and utilising a concise synthetic approach of sulfur extrusion, selenium insertion of the 1,2,3-dithiazoles. We created a small diverse library of compounds to contrast the two ring systems. This approach has highlighted new structure activity relationship insights and lead to the development of sub-micro molar anti-viral compounds with reduced toxicity. The 1,2,3-thiaselenazole represents a new class of potential compounds for the treatment of FIV and HIV.
A new approach to the synthesis of fused 1,2,3-thiaselenazoles-rare five-membered heterocycles that contain two different chalcogens-from the corresponding 1,2,3-dithiazoles and SeO was accomplished by selective exchange of S and Se atoms. The fused carbo- and heterocyclic units were indene, naphthalenone, cyclohexadienone, cyclopentadiene, benzoannulene, and benzoxazine. The molecular structures of two of the thiaselenadiazole products and one of the dithiazole precursors were confirmed by single-crystal X-ray diffraction. The reaction is highly solvent selective; it only takes place in solvents that contain a C=O group (e.g., DMF or tetramethylurea). According to DFT calculations, the reaction is thermodynamically favorable. Based on the DFT calculations and Se NMR spectroscopy, two tentative mechanisms that feature isomeric transition states and intermediates are suggested for the reaction via ring-opening addition of SeO to the S-X dithiazole bond (X=N or S). The DFT-calculated first adiabatic electron affinities of the compounds were chalcogen independent and positive in all cases, which assumes formation of thermodynamically stable radical anions (RAs). These calculated RAs featured either normal or abnormal elongation of the S1-X2 (X=S or Se) bond relative to their neutral precursors and possessed π* or σ* SOMOs, respectively.
We report our investigations into the underlying differences between 1,2,3-dithiazole and their ultra-rare counterpart, 1,2,3-thiaselenazole. This rare 1,2,3-thiaselenazole chemotype was afforded by sulfur extrusion and selenium insertion into the preconstructed 1,2,3-dithiazoles. We built a library of matched paired compounds to compare and contrast the two ring systems. This led to the development of both narrow and broad-spectrum antimicrobial compounds with sub-micro molar potency, limited to no toxicity and a further understanding of the transition state electronics through molecular simulations. We also identified the potent 4,5,6-trichlorocyclopenta[d][1,2,3]thiaselenazole 11a, for use against Candida albicans, Cryptococcus neoformans var. grubii, Staphylococcus aureus and Acinetobacter baumannii, all of which have limited clinical treatment options. The 1,2,3-thiaselenazole represents a new class of potential compounds for the treatment of a host of multi-resistant hospital derived infections.
Abstract:A new general protocol for synthesis of fused 1,2,3-dithiazoles by the reaction of cyclic oximes with S 2 Cl 2 and pyridine in acetonitrile has been developed. The target 1,2,3-dithiazoles fused with various carbocycles, such as indene, naphthalenone, cyclohexadienone, cyclopentadiene, and benzoannulene, were selectively obtained in low to high yields. In most cases, the hetero ring-closure was accompanied by chlorination of the carbocyclic moieties. With naphthalenone derivatives, a novel dithiazole rearrangement (15Ñ13) featuring unexpected movement of the dithiazole ring from α-to β-position, with respect to keto group, was discovered. Molecular structure of 4-chloro-5H-naphtho[1,2-d][1,2,3]dithiazol-5-one 13 was confirmed by single-crystal X-ray diffraction. Electrochemical properties of 13 were studied by cyclic voltammetry and a complex behavior was observed, most likely including hydrodechlorination at a low potential.
A new synthetic pathway to four substituted imidazoles from readily available 2-((4-aryl(thienyl)-5H-1,2,3-dithiazol-5-ylidene)amino)phenols has been developed. Benzo[d]oxazol-2-yl(aryl(thienyl))methanimines were proved as key intermediates in their synthesis. The formation of an imidazole ring from two methanimine derivatives likely includes the opening of one benzoxazole ring followed by ring closure by intermolecular nucleophilic attack of the N-methanimine atom to a carbon atom of another methanimine.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.