1,2,3-Oxadiazoles

Although simple 1,2,3-oxadiazoles are unknown, there are plenty of stable derivatives. This type of ring system is very well represented by mesoionic sydnones and sydnonimines, several of which are endowed with biological activity. The theoretical reaction of nitric oxide with alkenes and alkynes to give 1,2,3-oxadiazoline and 1,2,3-oxadiazolidines has been examined and new 1,2,3-oxadiazole N-oxides have been prepared by reaction of nitric oxide with alkyllithium reagents. The first examples of stable, uncharged 1,2,3-oxadiazoline and 1,2,3-oxadiazolidine rings have been described. New metallation reactions have been established for sydnones and sydnonimines whereby substituents may be introduced at a choice of different positions. 3-Arylsydnones have emerged as good directors of ortho-lithiation. Frontier molecular orbital control and substituent effects combine effectively in achieving regiospecific 1,3-dipolar cycloadditon of sydnones and unsymmetrical alkynes to form substituted pyrroles for biological applications. The biological activity associated with sydnonimines is attributed primarily to their nitric oxide-releasing properties. Several new derivatives of sydnones, sydnonimines, and glycoside and β-lactam conjugates have been prepared and their biological profiles established.