The synthesis of new 5-aminoimidazoles as potential antifungal agents

Abstract

5-Aminoimidazoles are attractive building blocks in chemical synthesis because they are key components in many bioactive compounds. Few reports on the chemistry of these compounds appear in the literature due to their known instability [1,2]. In our research group, 5-amino-4-cyanoformimidoyl imidazoles 1 are easily accessed by an efficient method. Previous studies on the reactivity of imidazoles 1 showed that the 4- cyanoformimidoyl group reacts with primary aromatic hydrazines in acidic medium with elimination of ammonia to generate α-phenylhydrazonoyl cyanides 2 (R= H). The antimicrobial activity of compounds 2 was assessed, and the in vitro screening identified one hit compound as active in C. albicans and C. krusei. These results prompted us to prepare new analogues with diverse hydrazonoyl moieties, in order to study their antibacterial and antifungal activities and to establish the structure-activity relationship (SAR). Here we report the reaction of imidazoles 1 with N-methyl phenylhydrazine and 1- aminopiperidine to generate the corresponding α-phenylhydrazonoyl cyanides 2 and 3 (Figure 1). The synthetic approaches will be discussed.