Studies on the Synthesis of the Fluorescent Hypermodified Nucleoside.

我们已经通过Wittig或Heck反应作为关键步骤实现了标题化合物Wybuosine的碱基Wybuine的合成。类似的Wittig方法和改进的方法都没有影响我们的目标化合物3-β-D-呋喃核糖的合成(1)。另一方面，核苷水平上的Heck反应成功地得到了1，2，4，4，6，6，6，6，6，6，6，5，5，6，6，5，6，6，6，6，6，6，6，6，6，6，6，6，6，6，6，6，6，6，5，5，6，5，5，5，5，5，6，5，5，5，5，5，5，5，5，5，5，5，5，5，5，5，5，4，5，5，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，为了开发立体选择性合成1，2，3，4，6，6，6，6，6，6，6，5，6-二甲基-2，4-三甲基-4，4，4，4，5，5，6，5，5，6-二甲基-4，4-三甲基-4，4，4，4，5，5，5，5，5，5，5，5，5，5，6，5，5，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4由于没有一个得到肯定的结果，我们集中在合成1的前体(S)-4，9-dihydro-alpha-[(methoxycarbonyl)amino]-4，6-dimethyl-9-oxo-3-(2，3，5-tri-omicron-acetyl-beta-D-ribofuranosyl)-3H-imidazo[1，2-alpha]purine-7-butanole酸(2)与它的非对映异构体的分离上。分离采用反相体系[乙腈-0.02M磷酸二氢钠(15：85，v/v)]。化合物2用三甲基硅基重氮甲烷处理，然后脱乙酰基，首次得到立体化学纯的I。这样得到的化合物1在N-糖苷键上经历了异常快速的水解，其速度与报道的Wybuosine的速度相同。由于1的2‘，3’，5‘-三甲氧基乙酰基衍生物比1稳定得多，故应通过其三乙酸酯进行分离和鉴定。

We had already achieved the synthesis of wybutine, the base of the title compound, wybutosine, by means of the Wittig or the, Heck reaction as a key step. Neither similar Wittig approach nor the modified procedure effected the synthesis of our target compound, 3-beta-D-ribofuranosylwye (1). On the other hand, the Heck reaction at the nucleoside level successfully afforded 1. This product, however, proved to be contaminated by its diastereomer. In order to develop a stereoselective synthesis of 1, we attempted several recent methods of C-C bond forming reactions as well as modification of the Heck reaction. Because none of them gave a positive result, we focused on separation of (S)-4,9-dihydro-alpha-[(methoxycarbonyl)amino]-4,6-dimethyl-9-oxo-3-(2,3,5-tri-omicron-acetyl-beta- D-ribofuranosyl)-3H-imidazo[1,2-alpha]purine-7-butanole acid (2), a precursor for the synthesis of 1, from its diastereomer by high-performance liquid chromatography. The separation was attained by use of a reversed-phase system [acetonitrile-0.02 M aqueous sodium dihydrogen phosphate (15:85, v/v)]. Compound 2 was treated with trimethyl- silyldiazomethane followed by deacetylation to afford stereochemically pure I for the first time. Compound 1 thus obtained underwent unusually fast hydrolysis at the N-glycosidic bond and the rate was of the same order of magnitude as that reported for wybutosine. Because 2',3',5'-tri-omicron-acetyl derivative of 1 proved much more stable than 1, isolation and identification of wybutosine should be done through its triacetate.