利用苄氧羰基保护高效合成核苷芳氧基磷酰胺酯前药
Efficient synthesis of nucleoside aryloxy phosphoramidate prodrugs utilizing benzyloxycarbonyl protection.
作者信息
Cho Jong Hyun, Amblard Franck, Coats Steven J, Schinazi Raymond F
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, Atlanta, GA 30033, USA.
出版信息
Tetrahedron. 2011 Jul 29;67(30):5487-5493. doi: 10.1016/j.tet.2011.05.046.
Abstract
An efficient method for the synthesis of nucleoside phosphoramidates prodrugs (6a-f) has been developed that employs a simple protection/deprotection sequence of the nucleoside with benzyloxycarbonyl (Cbz). The coupling reaction of Cbz-protected derivatives (5a-f) with phenyl-(ethoxy-L-alaninyl)-phosphorochloridate (7), followed by Cbz group removal by hydrogenolysis provided the phenyl phosphoramidate ProTides (6a-f) in excellent overall yields.
摘要
已开发出一种合成核苷亚磷酰胺酯前药（6a - f）的有效方法，该方法采用核苷与苄氧羰基（Cbz）进行简单的保护/脱保护序列。Cbz保护的衍生物（5a - f）与苯基 -（乙氧基 - L - 丙氨酰基） - 磷酰氯（7）的偶联反应，随后通过氢解去除Cbz基团，以优异的总收率得到苯基亚磷酰胺酯前药（6a - f）。
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