title: An Efficient Route to beta-D-Isoxazolidinyl Nucleosides via Diastereoselective Michael Addition of Hydroxylamine to Unsaturated Esters.
abstract: Enantioselective syntheses of beta-D-isoxazolidinyl pyrimidine and purine nucleosides are described. Michael addition of N-methylhydroxylamine to alpha,beta-unsaturated esters was 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 N(4)-benzoylcytosine using TMSOTf as a Lewis acid yielded the corresponding nucleoside derivatives. The related purine analogue was produced by the BF(3).Et(2)O-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.
authors.affiliation: 29 Washington Place, New York University, Department of Chemistry, New York, New York 10003.
authors.forename: Yuejun
authors.initials: Y
authors.lastname: Xiang
authors.forename: Hung-Jang
authors.initials: HJ
authors.lastname: Gi
authors.forename: Deqiang
authors.initials: D
authors.lastname: Niu
authors.forename: Raymond F.
authors.initials: RF
authors.lastname: Schinazi
authors.forename: Kang
authors.initials: K
authors.lastname: Zhao