Quinoxaline derivatives of severalalkaloids

Abstract

New quinoxaline derivatives were prepared by reaction of 2-quinoxalinehydroximoylbromide with the alkaloids anabasine, cytisine, and salsoline.Quinoxaline derivatives, which exhibit a broad spectrum of biological activity, are some of the most synthesized of all classes of N-containing heterocyclic compounds [1]. The quinoxaline ring in nature is most often condensed into more complicated cyclic systems, the most well-known of which is riboflavin (vitamin B 2 ).Two quinoxaline drugs are currently widely used in medical practice. These are quinoxidine and dioxidine, which have significant chemotherapeutic activity and are used for acute bacterial infections that are difficultly treated by other antimicrobial agents [2].Our goal was to synthesize new quinoxaline derivatives containing fragments of several alkaloids of plant origin in their structure.The key compound in the synthesis of the alkaloid derivatives of quinoxaline-2-hydroxamic acid was 2-quinoxalinehydroximoylbromide, which was synthesized by successive transformations of 2-methylquinoxaline (1). In the first step, 2-quinoxalinecarbonitrile (2) was prepared in 50% yield from 2-methylquinoxaline by oxidative ammonolysis by the method developed by us previously [3]. Then, amidoxime 3 was synthesized in good yield from 2 by the action of NH 2 OH under mild conditions and was converted by diazotization with NaNO 2 in dilute HBr into hydroximoylbromide 4.The resulting bromo derivative could easily add primary and secondary amines with elimination of HBr. In our instance, the secondary amines were the alkaloids anabasine (5a), cytisine (5b), and salsoline (5c). The reaction between 4 and the alkaloids at the NH center occurred smoothly under mild conditions to produce the corresponding quinoxaline alkaloid derivatives 6-8.