Design, Synthesis, Antiviral, and Cytostatic Evaluation of Novel Isoxazolidine Analogs of Homonucleotides

Abstract

Moderate diastereoselectivities (d.e. 2-62%) of isoxazolidine homonucleotides were observed for cycloadditions between N-methyl-C-(diethoxyphosphoryl)nitrone and N-allyl nucleobases, with trans-isoxazolidines predominating. The stereochemistry of the substituted isoxazolidines was established based on 2D NOE experiments performed for uracil-containing cycloadducts. The cis- and trans-isoxazolidine phosphonates obtained herein were evaluated in vitro for activity against a broad range of DNA and RNA viruses. None of the compounds were endowed with antiviral activity at subtoxic concentrations, but some of them were found to inhibit the proliferation of L1210 cells with IC50 values in the range of 33-100 µM.