2',3'-di-O-tert-butyldimethylsilyladenine-9-β-D-arabinofuranoside | 87418-94-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 2',3'-di-O-tert-butyldimethylsilyladenine-9-β-D-arabinofuranoside
• 英文别名: 2,3-disilylated arabinoadenosine；2',3'-O-di(tert-butyldimethylsilyl)vidarabine；[(2R,3R,4S,5R)-5-(6-aminopurin-9-yl)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]oxolan-2-yl]methanol
• CAS: 87418-94-8
• 化学式: C₂₂H₄₁N₅O₄Si₂
• 分子量: 495.77
• InChiKey: GAMKBDYUNFPWRM-DFYYWFRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.08
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  118
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2',3'-di-O-tert-butyldimethylsilyladenine-9-β-D-arabinofuranoside 在 四氮唑 、 叔丁基过氧化氢 、 triethylamine tris(hydrogen fluoride) 作用下， 以 四氢呋喃 为溶剂， 生成 2,2-Dimethyl-thiopropionic acid S-(2-{[(2R,3S,4S,5R)-5-(6-amino-purin-9-yl)-3,4-dihydroxy-tetrahydro-furan-2-ylmethoxy]-[2-(2,2-dimethyl-propionylsulfanyl)-ethoxy]-phosphoryloxy}-ethyl) ester
  参考文献：
  名称：

  Prodrugs of Ara-CMP and Ara-AMP with aS-Acyl-2-thioethyl (SATE) Biolabile Phosphate Protecting Group: Synthesis and Biological Evaluation

  摘要：

  The bis(S-pivaloyl-2-thioethyl) phosphotriesters of Ara-C and Ara-A were synthesized as potential bioreversible mononucleotide prodrugs. Some N- and O-acylated derivatives were also prepared with the aim to modify the lipophilicity of the title pronucleotides. Compounds were tested far their antitumor/antiviral activity against a variety of tumor cells and viruses.

  DOI：

  10.1080/15257779908041616
• 作为产物：
  描述：

  9-<2,3,5-tris-O-(tert-butyldimethylsilyl)-β-D-arabinofuranosyl>adenine 在 三氟乙酸 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 以58%的产率得到2',3'-di-O-tert-butyldimethylsilyladenine-9-β-D-arabinofuranoside
  参考文献：
  名称：

  一系列细胞色素 P4503A 激活的前药（HepDirect 前药）的设计、合成和表征，可用于将基于磷（上）酸盐的药物靶向肝脏§

  摘要：

  描述了一类新的磷酸盐和膦酸盐前药，称为 HepDirect 前药，它结合了快速肝脏裂解的特性与高血浆和组织稳定性，以实现肝脏中药物水平的增加。前药是取代的环状 1,3-丙酸酯，设计用于经历由主要在肝脏中表达的细胞色素 P(450) (CYP) 催化的氧化裂解反应。本文报道了在 C4 上含有芳基取代基的前药系列的发现及其用于将基于核苷的药物递送至肝脏的用途。阿糖腺苷、拉米夫定 (3TC) 和阿糖胞苷的 5'-单磷酸酯前药以及膦酸阿德福韦在暴露于肝脏匀浆后显示出裂解，并在血液和其他组织中表现出良好的稳定性。前药裂解需要在顺式构型中存在芳基，但相对独立于 C4 的核苷和绝对立体化学。机理研究表明，前药裂解通过初始 CYP3A 催化氧化为中间体开环一元酸，随后通过 β-消除反应转化为磷酸（on）酸酯和芳基乙烯基酮。在原代大鼠肝细胞和正常大鼠中比较 3TC 和相应的 HepDirect 前药的研究表

  DOI：

  10.1021/ja031818y

文献信息

• Ring-Open Analogues of Adenine Nucleoside. Aminoacyl Derivatives of Cyclo- and Acyclo-Nucleosides
  作者：Gholam H. Hakimelahi、Morteza Zarrinehzad、Ali A. Jarrahpour、Hashem Sharghi

  DOI：10.1002/hlca.19870700127

  日期：1987.2.4

  The synthesis of acyclic analogues of ribo- and deoxyribonucleosides is described. These compounds (Table 3) are both poor substrates and poor inhibitors of adenosine deaminase. The synthesis of dinucleotides from these analogues is also described, and the activity along with the inhibitory properties of some of them are studied against deaminase enzyme. These nucleotides are resistant to degradation

  描述了核糖核苷和脱氧核糖核苷的无环类似物的合成。这些化合物（表3）都是差的底物和差的腺苷脱氨酶抑制剂。还描述了由这些类似物合成二核苷酸，并研究了其中一些的活性及其对脱氨酶的抑制特性。这些核苷酸抗磷酸二酯酶降解。浸渍在硅胶上的HCl是用于制备无环核苷的氯甲基醚前体的极佳试剂。开发了一种通用且快速的程序来制备和分离机器人核糖和阿拉伯核糖核苷的5'-氨基酰基衍生物。喹啉在没有外消旋作用下对氨基酰化有显着影响。化合物35a，b在体外具有显着的抗病毒作用。还开发了将无环核糖核苷13e，f转化为无环脱氧核糖核苷11e，f的方法。
• Stereoselective synthesis of nucleoside monophosphate HepDirect™ prodrugs
  作者：K. Raja Reddy、Serge H. Boyer、Mark D. Erion

  DOI：10.1016/j.tetlet.2005.04.103

  日期：2005.6

  Synthesis of HepDirect™ prodrugs of nucleoside monophosphates via phosphorylation with a chiral reagent forms a new asymmetric center at phosphorus and produces two diastereomers. Coupling of chiral phosphoramidite 6 derived from (S)-diol 5 with ara-A followed by oxidation of the intermediate phosphite gave ara-AMP prodrugs 8 (4S,2S isomer) and 9 (4S,2R isomer). Several methods were explored to identify

  通过与手性试剂的磷酸化作用合成单磷酸核苷的HepDirect™前药在磷上形成一个新的不对称中心，并产生两个非对映异构体。手性的亚磷酰胺偶联6从（派生小号） -二醇5通过中间亚磷酸酯的氧化与ARA-A，接着得到ARA-AMP的前药8（4小号，2小号异构体）和9（4小号，2 - [R异构体）。探索了几种方法来鉴定每种非对映异构体的选择性合成途径。描述了对ARA-AMP前药8和9的两种成功的立体选择方法。
• Reaction intermediate analogues as bisubstrate inhibitors of pantothenate synthetase
  作者：Zhixiang Xu、Wei Yin、Leonardo K. Martinelli、Joanna Evans、Jinglei Chen、Yang Yu、Daniel J. Wilson、Valerie Mizrahi、Chunhua Qiao、Courtney C. Aldrich

  DOI：10.1016/j.bmc.2014.01.017

  日期：2014.3

  The biosynthesis of pantothenate, the core of coenzyme A (CoA), has been considered an attractive target for the development of antimicrobial agents since this pathway is essential in prokaryotes, but absent in mammals. Pantothenate synthetase, encoded by the gene panC, catalyzes the final condensation of pantoic acid with beta-alanine to afford pantothenate via an intermediate pantoyl adenylate. We describe the synthesis and biochemical characterization of five PanC inhibitors that mimic the intermediate pantoyl adenylate. These inhibitors are competitive inhibitors with respect to pantoic acid and possess submicromolar to micromolar inhibition constants. The observed SAR is rationalized through molecular docking studies based on the reported co-crystal structure of 1a with PanC. Finally, whole cell activity is assessed against wild-type Mtb as well as a PanC knockdown strain where PanC is depleted to less than 5% of wild-type levels. (C) 2014 Elsevier Ltd. All rights reserved.