Synthesis of novel isoxazolidine analogues of homonucleosides

A general method for the synthesis of nucleobase-derived nitrones 4a-e by treatment of N-(2-oxoethyl)nucleobases with N-methylhydroxylamine is reported. The nitrones 4a-e were applied in the synthesis of isoxazolidine homonucleosides. Moderate diastereoselectivities (de 28-82%) were observed for cycloadditions between nitrones 4a-e and allyl alcohol with cis-isoxazolidines predominating. The stereochemistry of the substituted isoxazolidines was established based on an analysis of 2D NOE experiments for uracil-containing cycloadducts 6a and 7a. Cycloadditions of uracil-based nitrone 4a with vinyl-, allyl-, vinyloxymethyl- and allyloxymethylphosphonates gave the respective phosphonylated cis-isoxazolidines as the major adducts.