AN EFFICIENT SYNTHESIS OF 2-SELENOURIDINE AND ITS PHOSPHORAMIDITE PRECURSOR
AN EFFICIENT SYNTHESIS OF 2-SELENOURIDINE AND ITS PHOSPHORAMIDITE PRECURSOR
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DOI：
10.3987/com-15-13349
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发表时间：
2016-01-01
期刊：
影响因子：
0.6
通讯作者：
Koketsu, Mamoru
中科院分区：
文献类型：
--
作者：
Kogami, Masakazu;Davis, Darrell R.;Koketsu, Mamoru
我们描述了一种有效的和可扩展的合成路线，天然存在的2-硒尿苷（（SeU）-U-2）和其适当保护的衍生物的亚磷酰胺合成。从已知的完全TBDMS保护的硫代尿苷，通过甲基硫代尿苷与NaHSe的反应合成相应的硒代尿苷，然后将其完全脱保护而不影响硒代羰基部分以得到（SeU）-U-2。接着，（SeU）-U-2以81%的产率经四个步骤转化为2 ′-O-TBDMS-5 ′-O-DMT衍生物，所述四个步骤包括在O3 ′和O 5 ′引入二叔丁基亚甲硅烷基（DTBS）、O2 ′-甲硅烷基化、DTBS的选择性裂解和DMT引入。该合成路线能够以优异的产率以克级规模制备（SeU）-U-2及其亚磷酰胺前体。此外，预测的C3 '-endo构象偏好的（SeU）-U-2的实验证实了NMR光谱。
We describe an efficient and scalable synthetic route to the natural occurring 2-selenouridine ((SeU)-U-2) and its suitably protected derivative for phosphoramidite synthesis. From known fully TBDMS-protected thiouridine, the corresponding selenouridine was synthesized via the reaction of methylthiouridine with NaHSe, which was then completely deprotected without affecting the selenocarbonyl moiety to deliver (SeU)-U-2. Next, (SeU)-U-2 was converted into the 2'-O-TBDMS-5'-O-DMT derivative in 81% yield over four steps including di-tert-butylsilylene (DTBS) introduction at O3' and O5', O2'-silylation, selective cleavage of DTBS, and DMT introduction. This synthetic route enabled gram-scale preparation of both (SeU)-U-2 and its phosphoramidite precursor in excellent yields. Furthermore, the predicted C3'-endo conformational preference of (SeU)-U-2 was experimentally confirmed by NMR spectroscopy.