外消旋 N-氨甲酰核苷的高效合成：在磷酰胺酸前药合成中的应用。
Efficient synthesis of exo-N-carbamoyl nucleosides: application to the synthesis of phosphoramidate prodrugs.
机构信息
Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine , and Veterans Affairs Medical Center, Decatur, Georgia 30033, United States, and RFS Pharma, LLC , 1860 Montreal Road, Tucker, Georgia 30084, United States.
出版信息
Org Lett. 2012 May 18;14(10):2488-91. doi: 10.1021/ol300777p. Epub 2012 May 3.
Abstract
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-N(6)-group of adenosine analogue 1 with alkyl/and aryl chloroformates under optimized conditions provided the N(6)-carbamoyl adenosines (2a-j) in good to excellent yields. The reaction of N(6)-Cbz-protected nucleosides (5a-c) with phenyl phosphoryl chloride (7) using t-BuMgCl followed by catalytic hydrogenation afforded the corresponding phosphoramidate pronucleotides (8a-c) in excellent yield.
摘要
开发了一种利用 N-甲基咪唑 (NMI) 保护嘌呤核苷 6-外氨基的有效保护基方法，可与各种氯甲酸酯反应。在优化条件下，阿糖腺苷类似物 1 的外 N(6)-氨基与烷基/芳基氯甲酸酯反应，以良好至优异的收率得到 N(6)-氨甲酰腺苷 (2a-j)。用 t-BuMgCl 使 N(6)-Cbz 保护的核苷 (5a-c) 与苯膦酰氯 (7) 反应，然后催化氢化，可得到相应的磷酰胺酯前核苷 (8a-c)，产率优异。
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3
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