Ring Distortion Diversity‐Oriented Approach to Fully Substituted Furoxans and Isoxazoles

Abstract

A regioselective method for an assembly of pharmacologically relevant fully substituted furoxans and isoxazoles using the ring distortion diversity‐oriented approach through the one‐pot ring cleavage/nucleophilic addition/oxidation cascade of monosubstituted furoxans was developed. The described synthetic strategy is highly regioselective and provides single furoxan regioisomers upon utilization of N‐ or S‐nucleophiles. Utilization of the cyanide‐anion as a nucleophile in the same reaction cascade afforded a series of rather rare fully substituted isoxazoles incorporating vicinal nitro and amino functionalities. In addition, synthesized disubstituted furoxans revealed an ability to release NO indicating their strong potential as pharmacologically oriented drug candidates for various biomedical applications.

Regioselective Synthesis of NO-Donor (4-Nitro-1,2,3-triazolyl)furoxans via Eliminative Azide–Olefin Cycloaddition

“…Moreover, biomedical applications of simple heterocyclic NO donors along with their hybridization with other pharmacophoric scaffolds were found to be promising for the creation of new medications to overcome the issue of multidrug resistance [15][16][17]. A variety of heterocyclic NO donors (furoxans [18][19][20][21][22], azasydnones [23,24], sydnone imines [25], triazole oxides [26] and pyridazine dioxides [27]) were synthesized and evaluated for their pharmacological potency so far (Figure 1).…”