195608-76-5Relevant academic research and scientific papers
An efficient route to β-D-isoxazolidinyl nucleosides via diastereoselective Michael addition of hydroxylamine to unsaturated esters
Xiang, Yuejun,Gi, Hung-Jang,Niu, Deqiang,Schinazi, Raymond F.,Zhao, Rang
, p. 7430 - 7434 (1997)
Enantioselective syntheses of β-D-isoxazolidinyl pyrimidine and purine nucleosides are described. Michael addition of N-methylhydroxylamine to α,β-unsaturated esters were investigated. Both E- and Z-esters 10E and 10Z produced the same intermediates which were cyclized to isoxazolidin-5-ones 8 with high diastereoselectivity. The major isoxazolidin-5-one 8a was reduced and acetylated to acetate 11 for the preparation of nucleosides. The coupling reaction of acetate 11 with silylated thymine, uracil, and N4- benzoylcytosine using TMSOTf as a Lewis acid yielded the corresponding nucleoside derivatives. The related purine analogue was produced by the BF3·Et2O-catalyzed condensation of acetate 11 with silylated 6- chloropurine. The predominant formation of the cis isomers for both pyrimidine and purine analogues was unexpected and the reaction mechanism was investigated. The nucleoside intermediates were converted to the corresponding 1,2-diols, which were latter oxidized and reduced to the desired monoalcohol products such as 14, 16, 19, and 24.
