New 4-aryl-1,3,2-oxathiazolylium-5-olates: Chemical synthesis and photochemical stability of a novel series of S-nitrosothiols

• Published in: Bioorganic & medicinal chemistry letters 2018-04, Vol.28 (6), p.1106-1110
• Main Authors: Eilertsen, Monica, Allin, Steve M., Pearson, Russell J.
• Format: Article
• Language: English
• Subjects: Dose-Response Relationship, Drug; Molecular Structure; Nitric oxide; NO-donating; Oxathiazolylium-5-olates; Photochemical Processes; Photochemical stability; S-nitrosothiols; S-Nitrosothiols - chemistry; Structure-Activity Relationship; Thiazoles - chemical synthesis; Thiazoles - chemistry
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2018.01.059

[Display omitted] S-nitrosothiols (RSNOs) remain one of the most popular classes of NO-donating compounds due to their ability to release nitric oxide (NO) under non-enzymatic means whilst producing an inert disulphide by-product. However, alligning these compounds to the different biological fields of NO research has proved to be problematic due to the inherent instability of such compounds under a variety of conditions including heat, light and the presence of copper ions. 1,3,2-Oxathiazolylium-5-olates (OZOs) represent an interesting subclass of S-nitrosothiols that lock the –SNO moiety into a five membered heterocyclic ring in an attempt to improve the compound’s overall stability. The synthesis of a novel series of halogen-containing OZOs was comprehensively studied resulting in a seven-step route and overall yields ranging between 21 and 37%. The photochemical stability of these compounds was assessed to determine if S-nitrosothiols locked within these mesoionic ring systems can offer greater stability and thereby release NO in a more controllable fashion than their non-cyclic counterparts.