Stereoselective synthesis of L-isoxazolidinyl thymidine from N-benzyl-1,2-di-O-isopropylidene-D-glyceraldehyde nitrone (BIGN)

A synthetic approach to L-isoxazolidinyl nucleosides is demonstrated by the stereoselective conversion of N-benzyl-1,2-di-O-isopropylidene-D-glycerald ehyde nitrone (BIGN) into cis and trans L-isoxazolidinyl thymidine. The met hodology consists of the 1,3-dipolar cycloaddition of BIGN with either viny l acetate or a vinyl base to give key intermediates that are easily transfo rmed into the target compound. The experimental results of the cycloadditio n reactions can be qualitatively explained by theoretical ab initio calcula tions. (C) 2000 Elsevier Science Ltd. All rights reserved.