Sodium—Liquid Ammonia Debenzylations in Nucleoside Synthesis1
Sodium—Liquid Ammonia Debenzylations in Nucleoside Synthesis1
复制标题
核苷合成中的钠-液氨脱苄基1
DOI：
10.1021/jo01035a525
复制
发表时间：
1964
影响因子：
3.6
通讯作者：
L. Goodman
中科院分区：
文献类型：
--
作者：
E. J. Reist;V. Bartuska;L. Goodman
因此，对于进一步的生物学评价和转化为潜在有用的类似物来说，数量上的III的合成变得非常重要。Glaudemans和Fletcher 4描述了2，3，5-三-O-苄基-D-阿拉伯呋喃甲酰氯(I)与6-苯甲酰胺基嘌呤的缩合反应，得到了所需的/3-核苷(III)。然而，合成的最后一步，即中间体II的催化氢解，只有在使用少量II时才方便。S-和N-苄基与氨水中钠的脱苄反应的大量例子使这成为一个合乎逻辑的选择；然而，令人惊讶的是，在文献中几乎没有提到用这种方法来裂解O-苄基。5本实验室最近的工作描述了6-氨基-3-O-苄基-5-S-苄基-6-脱氧-L，2-0-异亚丙基-5-硫代-L-呋喃葡萄糖在液氨中的作用下，O-和S-苄基的顺利脱除。我们希望引起对这种方法的关注，因为它的便利性和它在以前描述的O-脱苄方法的情况下的适用性。不合时宜。7在液氨中使用钠可以高产率地实现II到III的转化；这种对Glaudemans-Fletcher过程4的改进特别有利于III的大规模合成。值得注意的是，腺嘌呤环对钠在氨中作用的稳定性；有许多文献提到这种还原剂还原含氮杂环。9.
Accordingly the synthesis of III in quantity has become important both for further biological evaluation and for conversion to potentially useful analogs. The description by Glaudemans and Fletcher4 of the condensation of 2, 3, 5-tri-O-benzyl-D-arabinofuranosyl chloride (I) with 6-benzamido purine to give, after de-blocking, the desired/3-nucleoside (III) offered a practi-cal, direct route to III. However, the final step in the synthesis, the catalytic hydrogenolysis of the intermedi-ate II, was convenient only when small quantities of II were employed.An alternative technique for removal of the benzyl blocking group of II was sought and the use of sodium in liquid ammonia was investigated. The numerous ex-amples of debenzylation of S-and N-benzyl groups with sodium in ammonia made this a logical choice; sur-prisingly, however, there is virtually no mention in the literature of the use of this method for cleaving 0-benzyl groups. 5 Recent work in this laboratory6 789de-scribed the smooth removal of both the O-and S-benzyl group of 6-amino-3-0-benzyl-5-S-benzyl-6-deoxy-l, 2-0-isopropylidene-5-thio-L-idofuranose through the action of sodium in liquid ammonia. We wish to draw atten-tion to this method of O-debenzylation because of its convenience and its applicability in situations where previously described methods of O-debenzylation are. inappropriate. 7 It was possible to effect the conversion of II to III in high yield using sodium in liquid ammonia; this modification of the Glaudemans-Fletcher proce-dure4 is especially convenient for large-scale synthesis of III. The stability of the adenine ring to the action of sodium in ammonia is noteworthy; there are numerous references tothe reduction of nitrogen-containing heterocycles by this reducing agent. 9