Chen Xuemei, Wiemer David F
Department of Chemistry, University of Iowa, Iowa City, Iowa 52242-1294, USA.
J Org Chem. 2003 Aug 22;68(17):6597-604. doi: 10.1021/jo0300136.
alpha-Phosphono lactone derivatives of the nucleosides cytidine and cytosine arabinoside have been prepared from the corresponding nucleoside aldehydes. The stereochemical outcome of allylation reactions with these aldehydes was found to be dependent upon both the choice of protecting groups for the 2'- and 3'-hydroxyl groups and, to some extent, the nature of the Lewis acid catalyst employed. Ultimately, conditions were found that favored either the 5'R or 5'S diastereomer from different cytidine aldehydes, and gave some stereoselectivity in additions to an aldehyde derivative of ara-C. The resulting homoallylic alcohols were used as substrates in attempted Knovenagel and Horner-Wadsworth-Emmons condensations, but elimination was found to predominate over lactone formation under the conditions employed. The desired alpha-phosphono lactones could be prepared through a reaction sequence that included ring-closing metathesis on acrylate esters of the homoallylic alcohols, followed by reduction of the resulting alpha,beta-unsaturated lactones and carbon-phosphorus bond formation on enolates generated from the saturated lactones.
核苷胞苷和阿糖胞苷的α-膦酰内酯衍生物已由相应的核苷醛制备而成。发现这些醛的烯丙基化反应的立体化学结果既取决于2'-和3'-羟基保护基团的选择，也在一定程度上取决于所使用的路易斯酸催化剂的性质。最终，发现了有利于从不同胞苷醛生成5'R或5'S非对映异构体的条件，并在与阿糖胞苷的醛衍生物加成时具有一定的立体选择性。所得的高烯丙醇用作尝试进行克脑文格尔缩合和霍纳-沃兹沃思-埃蒙斯缩合的底物，但发现在所用条件下消除反应比内酯形成反应占主导。所需的α-膦酰内酯可通过一系列反应制备，该反应序列包括对高烯丙醇的丙烯酸酯进行闭环复分解反应，然后还原所得的α,β-不饱和内酯，并在由饱和内酯生成的烯醇盐上形成碳-磷键。
