Organocatalysis in the Synthesis of 1,2,3-Triazoyl-zidovudine Derivatives: Synthesis and Preliminary Antioxidant Activity

We describe herein the organocatalyzed synthesis and preliminary results of antioxidant activities of a range of 1,2,3-triazoyl-zidovudine derivatives. These hybrid compounds were synthesized in moderate to excellent yields by reacting zidovudine 1 with a variety of functionalized keto compounds 2, such as β-keto-esters, β-diketones, β-keto-amides, α-keto-nitriles, and β-keto-sulfones, in the presence of a catalytic amount of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (10 mol %). Furthermore, the synthesized compounds were screened for their in vitro antioxidant activity. Compounds 3 a, 3 d, 3 g, and 3 l inhibited the formation of reactive oxygen species (ROS) and lipid peroxidation in the prefrontal cortex and hippocampus of mice with similar potency and efficacy.