From Cyclopentadiene to Isoxazoline-Carbocyclic Nucleosides; Synthesis of Highly Active Inhibitors of Influenza A Virus H1N1

The synthesis of isoxazolino-carbocyclic nornucleosides incorporating a quinoline moiety was tuned through nitrosocarbonyl intermediate chemistry, and a range of adenine analogues were attained through the linear construction of purine heterocyclic rings. The synthesis hinges on exo-selective 1,3-dipolar cycloaddition of quinolinenitrile oxide to the 2,3-oxazanorborn-5-enes and simple elaboration of the cycloadducts. The nucleoside derivatives were initially tested for their inhibitory activity against a variety of viruses, including HBV, PTV and Flu A virus H1N1. High antiviral activities were found for compounds 22aA and 22bA in the case of Flu A H1N1. The synthesis of nornucleosides incorporating a quinoline moiety was tuned through the application of nitrosocarbonyl group chemistry. The synthesis hinges on exo-selective 1,3-dipolar cycloaddition of quinolinenitrile oxide to 2,3-oxazanorborn-5-enes and elaboration of the cycloadducts. The nucleosides were tested as inhibitors of a variety of viruses and some were found highly active against Flu A H1N1.