2-amino-6-chloro-9-[3,5-O-(tetraisopropyldisiloxane-1,3-diyl)-β-D-ribofuranosyl]purine | 87791-91-1

• 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-amino-6-chloro-9-[3,5-O-(tetraisopropyldisiloxane-1,3-diyl)-β-D-ribofuranosyl]purine
• 英文别名: 2-amino-6-chloro-9-(3,5-O-tetraisopropyldisiloxan-1,3-diyl-β-D-ribofuranosyl)purine；2-amino-6-chloro-9-(3,5-O-tetraisopropyldisiloxane-β-D-ribofuranosyl)-purine；(6aR,8R,9R,9aS)-8-(2-amino-6-chloropurin-9-yl)-2,2,4,4-tetra(propan-2-yl)-6a,8,9,9a-tetrahydro-6H-furo[3,2-f][1,3,5,2,4]trioxadisilocin-9-ol
• CAS: 87791-91-1
• 化学式: C₂₂H₃₈ClN₅O₅Si₂
• 分子量: 544.198
• InChiKey: RGIPAQUEWYOZIE-QTQZEZTPSA-N

物化性质

• 沸点：
  612.5±65.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.28
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  127
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-amino-6-chloro-9-[3,5-O-(tetraisopropyldisiloxane-1,3-diyl)-β-D-ribofuranosyl]purine 在 4-二甲氨基吡啶 、 四丁基氟化铵 、 对甲苯磺酸 、 溶剂黄146 、 三乙胺 、 4,4'-二氨基二苯乙烯-2,2'-二磺酸 作用下， 以 四氢呋喃 、 吡啶 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.17h， 生成 N²,O^5'-ditrityl-2-amino-6-chloro-9-[2-deoxy-2-fluoro-3-O-(tetrahydro-2-pyranyl)-β-D-ribofuranosyl]purine
  参考文献：
  名称：

  SYNTHESIS of 2′-DEOXY-2′-FLUOROGUANYL-(3′,5′)-GUANOSINE

  摘要：

  The protected analogue of 2-amnio-6-chloropurine arabinoside (3b) was subjected to reaction with diethylaminosulfur trifluoride (DAST) and subsequently treated with NaOAc in Ac2O/AcOH to give N-2, O-3', O-5'-triacetyl-2'-deoxy-2'-fluoroguanosine (5a). After deacetylation of the sugar moiety and protection of 5'-OH by a 4,4'-dimethoxytrityl group, this nucleoside component was converted to 2'-deoxy-2-fluoroguanyl-(3',5')-guanosine (6c, GfpG).

  DOI：

  10.1081/ncn-120016479
• 作为产物：
  描述：

  6-氯鸟嘌呤核苷 、 1,3二氯-1,1,3,3-四异丙基二硅氧烷 在 咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.75h， 以62%的产率得到2-amino-6-chloro-9-[3,5-O-(tetraisopropyldisiloxane-1,3-diyl)-β-D-ribofuranosyl]purine
  参考文献：
  名称：

  新的双修饰核苷的合成方法：虫草素和相关的2'-脱氧腺苷的同源物

  摘要：

  报道了虫草素（化合物20-25）和2'-脱氧腺苷（化合物11、13-15、18、19）的新型类似物的合成。为了从共同的起始化合物2-氨基-6-氯嘌呤核糖核苷进入3'-脱氧和2'-脱氧异构体系列，通过转化为2'，5'-的混合物来保护该前体和3′，5′--甲硅烷基化合物，然后在碳水化合物部分的2'-或3'-位置和基础成分的2-位置进行修饰。讨论了甲硅烷基基团异构化的观察。合成中的其他关键转化是自由基脱氧（碳水化合物部分），自由基碘化（为修饰碱基而定）和金属介导的官能化反应（碱基成分的区域特异性修饰）。通过紫外线，高场1 H和13 C NMR以及FAB HBMS数据确定了最终目标分子的结构及其纯度。所提出的合成方法具有一般性，并提供了进入多种双修饰核苷的途径。

  DOI：

  10.1016/s0040-4020(01)90496-x

文献信息

• Synthesis and cytotoxicity of 9-(2-deoxy-2-alkyldithio-β-<scp>D</scp>-arabinofuranosyl)purine nucleosides which are stable precursors to potential mechanistic probes of ribonucleotide reductases
  作者：Stanislaw F. Wnuk、Elzbieta Lewandowska、Dania R. Companioni、Pedro I. Garcia Jr、John A. Secrist III

  DOI：10.1039/b311504f

  日期：——

  adenine 5[prime or minute]-diphosphate. The arabino 2[prime or minute]-mercapto group might interact with the crucial thiyl radical at cysteine 439 leading to the inhibition of ribonucleotide reductases via formation of a Cys439-2[prime or minute]-mercapto disulfide bridge. The 2,6-diamino-, 2-amino-6-chloro- and 2-amino-6-methoxypurine ribosides were also converted to the corresponding 2[prime or

  合成了一系列2 [prime或min] -thiothiosidesides，作为核糖核苷酸还原酶的潜在抑制剂。用硫代乙酸钾处理3 [主要或分钟]，5 [主要或分钟] -O-TPDS-2 [主要或分钟] -O-（三氟甲磺酰基）腺苷得到2 [主要或分钟] -S的阿拉伯差向异构体-乙酰基-2 [伯或分钟]-硫代腺苷被脱乙酰化，以高收率得到9-（3,5-O-TPDS-2-硫基-小β-d-呋喃糖基）腺嘌呤。用偶氮二羧酸二乙酯-C（3）H（7）SH-THF处理后者，得到2 [伯或分钟]-丙基二硫化物，其被甲硅烷基化得到9-（2-脱氧-2-丙基二硫代-[小β]- d-阿拉伯呋喃糖基）腺嘌呤。随后进行甲苯磺酸化处理（O5 [prime or minutes]），并用焦磷酸酯取代甲苯磺酸酯，以稳定的形式提供了丙基混合二硫化物5 [prime or minutes] -O-diphosphate。其在用二硫
• プリンヌクレオシドの合成
  申请人：ギリアド ファーマセット エルエルシー

  公开号：JP2015227337A

  公开（公告）日：2015-12-17

  PROBLEM TO BE SOLVED: To provide compounds useful for treating conditions caused by viral factors.SOLUTION: The present invention provides compounds represented by formula (I) or formula (II) or salts thereof, and methods of synthesizing the same. (R1 is phenyl group or the like; R2 is H or the like; R3a and R3b are each independently H, a C1-10 alkyl group, or the like; R4 is H, a C1-10 alkyl group, a C3-10 cycloalkyl group, or the like; R5 is H or the like; R6 is H, CH3, or the like; R7 is H, an n-alkyl group, a cycloalkyl group, or the like; R8 is O (lower alkyl), O (lower cycloalkyl), or the like; and R9 is an NH2 group or the like.)

  要解决的问题：提供用于治疗由病毒因素引起的疾病的化合物。解决方案：本发明提供由式（I）或式（II）代表的化合物或其盐，以及它们的合成方法。（其中，R1是苯基或类似物；R2是H或类似物；R3a和R3b分别独立地是H、C1-10烷基或类似物；R4是H、C1-10烷基、C3-10环烷基或类似物；R5是H或类似物；R6是H、CH3或类似物；R7是H、n-烷基、环烷基或类似物；R8是O（较低烷基）、O（较低环烷基）或类似物；R9是NH2基团或类似物。）
• Robins, Morris J.; Wilson, John S.; Sawyer, Lindsay, Canadian Journal of Chemistry, 1983, vol. 61, p. 1911 - 1920
  作者：Robins, Morris J.、Wilson, John S.、Sawyer, Lindsay、James, Michael N. G.

  DOI：——

  日期：——
• 9-(2-<i>C</i>-Cyano-2-deoxy-β-<scp>d</scp>-<i>arabino</i>- pentofuranosyl)guanine, a Potential Antitumor Agent against B-Lymphoma Infected with Kaposi's Sarcoma-Associated Herpesvirus
  作者：Masaki Ohtawa、Satoshi Ichikawa、Yasuhiro Teishikata、Masahiro Fujimuro、Hideyoshi Yokosawa、Akira Matsuda

  DOI：10.1021/jm070032y

  日期：2007.5.1

  Several 9-(2-C-cyano-2-deoxy-l-beta-D-arabino-pentofuranosyl)purine derivatives were tested against Kaposi's sarcoma-associated herpesvirus (KSHV)-infected primary effusion lymphoma (PEL) cells. The guanine derivative (3, CNDAG), as well as the 2-amino-6-substituted-purine derivatives 4, 5, and 6, exhibited cell growth inhibitory activity against KSHV-infected cells, but showed no cytotoxicity against KSHV-negative cells at > 15 mu M concentrations. Therefore, it was found that compounds 3, 4, 5, and 6 showed selective cytotoxicity against PEL cells infected with KSHV.
• Synthesis of Stable Isotope Labeled Analogs of the Anti-Hepatitis C Virus Nucleotide Prodrugs PSI-7977 and PSI-352938
  作者：Byoung-Kwon Chun、Jinfa Du、Hai-Ren Zhang、Wonsuk Chang、Bruce S. Ross、Ying Jiang、Donghui Bao、Christine L. Espiritu、Meg Keilman、Holly M. Micolochick Steuer、Phillip A. Furman、Michael J. Sofia

  DOI：10.1080/15257770.2011.614308

  日期：2011.11

  In order to support bioanalytical LC/MS method development and plasma sample analysis in preclinical and clinical studies of the anti-hepatitis C-virus nucleotides, PSI-7977 and PSI-352938, the corresponding stable isotope labeled forms were prepared. These labeled compounds were prepared by addition reaction of the freshly prepared Grignard reagent (CD3MgI)-C-13 to the corresponding 2'-ketone nucleosides followed by fluorination of the resulting carbinol with DAST. As expected, these 2'-C-(trideuterated-C-13-methyl) nucleotide prodrugs showed similar anti-HCV activity to that of the corresponding unlabeled ones.