当前位置： X-MOL 学术 › Nucleosides Nucleotides Nucleic Acids › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Synthesis of 3'-amino-3'-deoxyguanosine and 3'-amino-3'-deoxyxyloguanosine monophosphate HepDirect prodrugs from guanosine.
Nucleosides, Nucleotides & Nucleic Acids ( IF 1.1 ) Pub Date : 2009-10-20 , DOI: 10.1080/15257770903307151
Brett C Bookser ₁ , Nicholas B Raffaele , K Raja Reddy , Kevin Fan , Wenjian Huang , Mark D Erion

Affiliation

The synthesis of 3′-amino-3′-deoxyguanosine and 3′-amino-3′-deoxyxyloguanosine monophosphate HepDirect prodrugs from guanosine is reported. Initial incorporation of N,N-dibenzylformamidino protection of the C2-amino of guanosine masked the reactivity of that group and simplified purification of subsequent analogues. The first key intermediate, 9-(2,5-bis-O-tert-butyldimethylsilyl-β-D-ribofuranosyl)-2-N-(N,N-dibenzylformamidino)guanine (3a), was prepared in 60% yield after recycling of the undesired 3′,5′-bis-O-protected byproduct (4a) by simple equilibration in methanol to a mixture of the two bis-O-protected compounds. Thus, protected, the 3′-position was manipulated to form the 3′-deoxyribo- or 3′-deoxyxylo-3′-azido derivatives (9 or 16, respectively). Further selective manipulations provided the cis-5′-monophosphate (3-chlorophenyl)-1,3-propanyl diester prodrugs (HepDirect prodrugs), 15 and 21. These HepDirect prodrugs were demonstrated to activate to their respective NTPs in rat hepatocytes.

Synthesis of 3′-Amino-3′-Deoxyguanosine and 3′-Amino-3′-Deoxyxyloguanosine Monophosphate Hepdirect Prodrugs from Guanosine

All authorsBrett C. Bookser,Nicholas B. Raffaele,K. Raja Reddy,Kevin Fan,Wenjian Huang &Mark D. Erionhttps://doi.org/10.1080/15257770903307151

Published online:

20 October 2009

中文翻译：

由鸟苷合成3'-氨基-3'-脱氧鸟苷和3'-氨基-3'-脱氧木胍一磷酸HepDirect前药。

据报道由鸟苷合成3'-氨基-3'-脱氧鸟苷和3'-氨基-3'-脱氧木胍单磷酸HepDirect前药。N，N-二苄基甲酰胺基对鸟嘌呤的C 2-氨基的初始保护掩盖了该基团的反应性并简化了后续类似物的纯化。第一关键中间体，9-（2,5-双- ø -叔丁基二-β-d-D-呋喃核糖基）-2- ñ - （Ñ，Ñ -dibenzylformamidino）鸟嘌呤（图3a）中的溶液在60％产率制备后通过简单地在甲醇中平衡为两种双-的混合物，可以回收不需要的3'，5'-双-O-保护的副产物（4a）O保护的化合物。因此，在保护下，操纵3'-位置以形成3'-脱氧核糖或3'-脱氧木糖-3'-叠氮基衍生物（分别为9或16）。进一步的选择性操作提供了顺式-5'-单磷酸（3-氯苯基）-1,3-丙二酯二元前药（HepDirect前药），15和21。这些HepDirect前药被证明可以激活大鼠肝细胞中各自的NTP。