A novel class of modified nucleosides: Synthesis of alkylidene isoxazolidinyl nucleosides containing thymine

The synthesis of hitherto unknown 1-[3-(hydroxymethyl)-2-methyl-4-methyleneisoxazolidin-5-yl]thymine (5), 1-{(Z)-[3(hydroxymethyl)-2-methylisoxazolidin-4-ylidene]methyl}- thymine (6), and 1-[(E)-[3-(hydroxymethyl)-2-methylisoxazolidin-5-ylidene]methyl}thymine (7) is described. The first compound can be regarded as a N,O-analogue of Entecavir and DMDC, which contains thymine as a nucleobase. The key allenic nucleobase was prepared in good yields starting from 2,3-dibromopropene. The subsequent 1,3-dipolar cycloaddition proceeded with good site selectivity to give 5 and regioisomeric nucleosides 6 and 7. ((c) Wiley-VCH Verlag GmbH & Co.