Efficient Synthesis of Exo-N-carbamoyl Nucleosides: Application to the Synthesis of Phosphoramidate Prodrugs
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- 作者：Jong Hyun Cho ; Steven J. Coats ; Raymond F. Schinazi
- 刊名：Organic Letters
- 出版年：2012
- 出版时间：May 18, 2012
- 年：2012
- 卷：14
- 期：10
- 页码：2488-2491
- 全文大小：241K
- 年卷期：v.14,no.10(May 18, 2012)
- ISSN：1523-7052
文摘
An efficient protection protocol for the 6-exo-amino group of purine nucleosides with various chloroformates was developed utilizing N-methylimidazole (NMI). The reaction of an exo-N6-group of adenosine analogue 1 with alkyl/and aryl chloroformates under optimized conditions provided the N6-carbamoyl adenosines (2a鈥?b>j) in good to excellent yields. The reaction of N6-Cbz-protected nucleosides (5a鈥?b>c) with phenyl phosphoryl chloride (7) using t-BuMgCl followed by catalytic hydrogenation afforded the corresponding phosphoramidate pronucleotides (8a鈥?b>c) in excellent yield.