9-(3,5-O-(tetraisopropylsiloxanediyl)-β-D-erythro-pentofuran-2-ulosyl)adenine | 90318-44-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 9-(3,5-O-(tetraisopropylsiloxanediyl)-β-D-erythro-pentofuran-2-ulosyl)adenine
• 英文别名: 3',5'-O-(tetraisopropyldisiloxane-1,3-diyl)-2'-ketoadenosine；(6aR,8R,9aR)-8-(6-aminopurin-9-yl)-2,2,4,4-tetra(propan-2-yl)-6a,9a-dihydro-6H-furo[3,2-f][1,3,5,2,4]trioxadisilocin-9-one
• CAS: 90318-44-8
• 化学式: C₂₂H₃₇N₅O₅Si₂
• 分子量: 507.737
• InChiKey: BOHJTGZLCAOZIQ-ZWDAVXSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.83
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  124
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  9-(3,5-O-(tetraisopropylsiloxanediyl)-β-D-erythro-pentofuran-2-ulosyl)adenine 在 吡啶 、 硼烷 、 sodium hydride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 18.0h， 生成 9-[(6aR,8R,9S,9aR)-2,2,4,4-tetra(propan-2-yl)spiro[6,6a,8,9a-tetrahydrofuro[3,2-f][1,3,5,2,4]trioxadisilocine-9,2'-oxolane]-8-yl]purin-6-amine
  参考文献：
  名称：

  [EN] COMPOUNDS
  [FR] COMPOSÉS

  摘要：

  本文披露了公式I的2'-螺环核苷及其衍生物，用于治疗感染丙型肝炎病毒或登革病毒的受试者。公式(I)中，z是从以下结构(II)所代表的基团a-o中选择的四元或五元环。其中*表示连接到2'-碳的位置。

  公开号：

  WO2012075140A1
• 作为产物：
  描述：

  腺苷 在 吡啶 、 chromium(VI) oxide 、 乙酸酐 作用下， 反应 1.0h， 生成 9-(3,5-O-(tetraisopropylsiloxanediyl)-β-D-erythro-pentofuran-2-ulosyl)adenine
  参考文献：
  名称：

  [EN] COMPOUNDS
  [FR] COMPOSÉS

  摘要：

  本文披露了公式I的2'-螺环核苷及其衍生物，用于治疗感染丙型肝炎病毒或登革病毒的受试者。公式(I)中，z是从以下结构(II)所代表的基团a-o中选择的四元或五元环。其中*表示连接到2'-碳的位置。

  公开号：

  WO2012075140A1

文献信息

• Nucleosides and nucleotides. LXIV. Synthesis of 2'-deoxy-8,2'-ethanoadenosine and 3'-deoxy-8,3'-ethanoadenosine.
  作者：HIROYUKI USUI、TOHRU UEDA

  DOI：10.1248/cpb.34.15

  日期：——

  2'-Deoxy-8, 2'-ethanoadenosine and its 3'-isomer were synthesized from 2'- and 3'-keto-adenosine derivatives. Treatment of 3', 5'-O-(tetraisopropyldisiloxane-1, 3-dilyl)-2'-ketoadenosine with ethoxycarbonylmethylenetriphenylphosphorane gave the 2'-ethoxycarbonylmethylene derivative, which was reduced to the 2'-hydroxyethyl derivative. This compound was converted to the 2'-iodoethyl-N6, N6-dibenzoyladenosine, which was cyclized by treatment with tri-n-butyltin hybride, then deprotected to furnish 2'-deoxy-8, 2'-ethanoadenosine. Photocyclization of a 2'-phenylthioethyl derivative also gave the ethano-cycloadenosine. 3'-Deoxy-8, 3'-ethanoadenosine was prepared from 2', 5'-di-O-(tert-butyldimethylsilyl)-3'-ketoadenosine via 2', 5'-di-O-acetyl-3'-deoxy-3'-phenylthioethyladenosine by photocyclization. The circular dichroism spectral features of these cycloadenosines are presented.

  2'-脱氧-8, 2'-乙基腺苷及其3'-异构体是从2'-和3'-酮腺苷衍生物合成的。将3', 5'-O-(四异丙基二硅氧烷-1, 3-二烯基)-2'-酮腺苷与乙氧基羧基亚甲基三苯基膦进行反应，得到2'-乙氧基羧基亚甲基衍生物，该衍生物被还原为2'-羟乙基衍生物。该化合物进一步转化为2'-碘乙基-N6, N6-二苯甲酰腺苷，并通过用三正丁基锡氢化物处理使其环化，随后去保护，生成2'-脱氧-8, 2'-乙基腺苷。2'-苯基硫乙基衍生物的光环化反应也产生了乙基环腺苷。3'-脱氧-8, 3'-乙基腺苷是通过2', 5'-二-O-(叔丁基二甲基硅氧基)-3'-酮腺苷，经过2', 5'-二-O-乙酰-3'-脱氧-3'-苯基硫乙基腺苷的光环化合成的。这些环腺苷的圆二色性光谱特征被展示。
• Highly Diastereoselective Synthesis of (2'S)-[2'-2H]-2'-Deoxyribonucleosides from the Corresponding Ribonucleosides
  作者：Etsuko Kawashima、Yukio Aoyama、Mohamed Radwan、Masayoshi Miyahara、Takeshi Sekine、Masatsune Kainosho、Yoshimasa Kyogoku、Yoshiharu Ishido

  DOI：10.1080/15257779508012375

  日期：1995.5.1

  Abstract The four (2′S)-[2′-2H]-2′-deoxynucleosides (>90 atom % 2H), were synthesized from the corresponding ribonucleosides involving six steps of reactions, i.e., oxidation of their 2′-hydroxyl group, stereoselective reductive deuteration of the resulting 2′-ketonucleoside intermediates with NaB2H4 in EtOH-H2O or EtOH, triflation, bromination with LiBr, highly stereoselective Bu3SnH-Et3B reduction

  摘要从相应的核糖核苷合成了四个（2'S）-[2'-2H] -2'-脱氧核苷（> 90原子％2H），涉及六个反应步骤，即2'-羟基的氧化，在EtOH-H2O或EtOH中用NaB2H4对所得2'-酮核苷中间体进行立体选择性还原氘化，三氟甲磺酸酯化，用LiBr溴化，高度立体选择性Bu3SnH-Et3B还原所得溴化物，最后进行掩蔽。
• Nucleosides and nucleotides. LXV Synthesis of 8,2'-methano- and 8,2'-ethanoadenosines.
  作者：HIROYUKI USUI、TOHRU UEDA

  DOI：10.1248/cpb.34.1518

  日期：——

  Treatment of 3', 5'-O-(tetraisopropyldisiloxane-1, 3-diyl)-2'-ketoadenosine (1) with methylenetriphenylphosphorane gave the 2'-methylene derivative (2). Hydroxylation of 1 with OsO4 gave the 2'-hydroxymethyladenosine (4), which was then converted to the 2'-phenylthiomethyl derivative (5). Photocyclization followed by deprotection of the product furnished 8, 2'-methanoadenosine (7), and adenosine fixed in a high-anti conformation. Oxidation of a 2'-hydroxyethylideneadenosine with OsO4 gave the 2'-dihydroxyethyladenosine (10), which was also converted to the 2'-(2-phenylthioethyl) derivative (11). The photocyclization of 11 and successive elimination of the hydroxyl group gave the 8, 2'-ethenoadenosine (13). Catalytic hydrogenation and deprotection of 13 afforded 8, 2'-ethanoadenosine (15). The circular dichroism spectral features of C-cycloadenosine are discussed.

  将 3'，5'-O-(四异丙基二硅氧烷-1，3-二基)-2'-酮腺苷 (1) 与亚甲基三苯基膦处理，可得到 2'-亚甲基衍生物 (2)。用 OsO4 对 1 进行羟基化反应，得到 2'- 羟甲基腺苷 (4)，然后将其转化为 2'- 苯硫甲基衍生物 (5)。对产物进行光环化和脱保护处理后，得到 8、2'-甲基腺苷（7）和以高反构象固定的腺苷。用 OsO4 氧化 2'-hydroxyethylideneadenosine 可以得到 2'-dihydroxyethyladenosine (10)，它还可以转化为 2'-(2-phenylthioethyl) 衍生物 (11)。11 的光环化和羟基的连续消除得到了 8,2'-乙烯腺苷（13）。对 13 进行催化氢化和脱保护处理后，得到了 8，2'-乙烯腺苷（15）。本文讨论了 C-胞二色谱的光谱特征。
• Structure−Activity Relationship of Purine Ribonucleosides for Inhibition of Hepatitis C Virus RNA-Dependent RNA Polymerase
  作者：Anne B. Eldrup、Charles R. Allerson、C. Frank Bennett、Sanjib Bera、Balkrishen Bhat、Neelima Bhat、Michele R. Bosserman、Jennifer Brooks、Christine Burlein、Steven S. Carroll、P. Dan Cook、Krista L. Getty、Malcolm MacCoss、Daniel R. McMasters、David B. Olsen、Thazha P. Prakash、Marija Prhavc、Quanlai Song、Joanne E. Tomassini、Jie Xia

  DOI：10.1021/jm030424e

  日期：2004.4.1

  to identify inhibitors of hepatitis C viral (HCV) replication, we report here the synthesis and evaluation of a series of nucleoside analogues and their corresponding triphosphates. Nucleosides were evaluated for their ability to inhibit HCV RNA replication in a cell-based, subgenomic replicon system, while nucleoside triphosphates were evaluated for their ability to inhibit in vitro RNA synthesis mediated

  作为识别丙型肝炎病毒 (HCV) 复制抑制剂的持续努力的一部分，我们在此报告了一系列核苷类似物及其相应的三磷酸盐的合成和评估。评估了核苷在基于细胞的亚基因组复制子系统中抑制 HCV RNA 复制的能力，而评估了核苷三磷酸抑制由 HCV RNA 依赖性 RNA 聚合酶 NS5B 介导的体外 RNA 合成的能力。2'-C-甲基腺苷和 2'-C-甲基鸟苷被确定为 HCV RNA 复制的有效抑制剂，并且发现相应的三磷酸盐是 HCV NS5B 介导的 RNA 合成的有效抑制剂。在基于细胞的测定中产生的数据证明了围绕活性核苷的相当严格的构效关系。发现 C2 上超过甲基的空间体积增加、甲基取代基的立体化学或区域化学的变化，或杂碱的特性变化超过内源性腺嘌呤或鸟嘌呤的变化，会导致抑制活性的丧失。结果突出了核糖构型 2'-和 3'-羟基药效团在基于细胞的测定中抑制 HCV RNA 复制的重要性，并证明包含 2
• Nucleic acid related compounds. 70. Synthesis of 2'(and 3')-deoxy-2'(and 3')-methyleneadenosines and bis(methylene)furan 4',5'-didehydro-5'-deoxy-2'(and 3')-methyleneadenosines. Inhibitors of S-adenosyl-L-homocysteine hydrolase and ribonucleotide reductase
  作者：Vicente Samano、Morris J. Robins

  DOI：10.1021/jo00025a029

  日期：1991.12

  Wittig treatment of 3',5'(or 2',5')-bis-O-silyl-2'(or 3')-ketoadenosine derivatives with methylenetriphenylphosphorane and deprotection gave the 2'(or 3')-deoxy-2'(or 3')-methyleneadenosines, respectively. Enzymatic deamination afforded the 2'(or 3')-deoxy-2'(or 3')-methyleneinosines. Treatment of 2'-O-(tert-butyldimethylsilyl)-3'-deoxy-3'-methylene-5'-O-tosyladenosine (14) with sodium 2-methyl-2-butoxide and deprotection gave 9-(3,5-dideoxy-3-methylene-beta-D-glycero-pent-4-enofuranosyl)adenine (20). Analogous treatment of a protected 2',5'-dideoxy-5'-iodo-2'-methyleneadenosine derivative gave 9-(2,5-dideoxy-2-methylene-beta-D-glycero-pent-4-enofuranosyl)adenine (22). Biochemical aspects of the putative mechanism-based inhibition of S-adenosyl-L-homocysteine hydrolase and ribonucleotide reductase by these compounds are discussed.