Synthesis of Analogues of Flazin, in Particular, Flazinamide, as Promising Anti-HIV Agents

Flazin isolated from the fruiting bodies of Suillus granulatus was found to possess weak anti‐HIV activity (EC50=2.36 μM, TI=12.1). To establish a SAR study, 46 flazin analogues were synthesized, and their anti‐HIV activities were evaluated in vitro. Among them, flazinamide (9a) showed the most potent activity with an EC50 value of 0.38 μM and a TI value of 312.0. The results suggested that appropriate substituents at positions 3, 1′, and 5′ of flazin might play a crucial role in determining their anti‐HIV activities, and that flazinamide can be considered as a promising, readily available anti‐HIV agent.