AN EFFICIENT SYNTHESIS OF 2-SELENOURIDINE AND ITS PHOSPHORAMIDITE PRECURSOR

作者：Kogami Masakazu; Davis Darrell R; Koketsu Mamoru^*

来源：Heterocycles, 2016, 92(1): 64-74.

DOI：10.3987/COM-15-13349

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.

• 出版日期2016-1-1