9-[2,5-bis-O-(tert-butyldimethylsilyl)-3-deoxy-β-D-glyceropent-3-enofuranosyl]adenine | 877465-92-4

• 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-[2,5-bis-O-(tert-butyldimethylsilyl)-3-deoxy-β-D-glyceropent-3-enofuranosyl]adenine
• 英文别名: 9-[(2R,3R)-3-[tert-butyl(dimethyl)silyl]oxy-5-[[tert-butyl(dimethyl)silyl]oxymethyl]-2,3-dihydrofuran-2-yl]purin-6-amine
• CAS: 877465-92-4
• 化学式: C₂₂H₃₉N₅O₃Si₂
• 分子量: 477.754
• InChiKey: HRLDAGGDQPEZDE-OXQOHEQNSA-N

物化性质

• 沸点：
  534.7±60.0 °C(Predicted)
• 密度：
  1.13±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.23
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  97.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  9-[2,5-bis-O-(tert-butyldimethylsilyl)-3-deoxy-β-D-glyceropent-3-enofuranosyl]adenine 在 二甲基二环氧乙烷 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 2.5h， 生成 N-[9-[(1S,3R,4R,5R)-4-[tert-butyl(dimethyl)silyl]oxy-1-[[tert-butyl(dimethyl)silyl]oxymethyl]-2,6-dioxabicyclo[3.1.0]hexan-3-yl]purin-6-yl]-2,2-dimethylpropanamide
  参考文献：
  名称：

  Anti versus Syn Opening of Epoxides Derived from 9-(3-Deoxy-β-d-glycero-pent-3-enofuranosyl)adenine with Me₃Al:  Factors Controlling the Stereoselectivity

  摘要：

  [graphics]Upon epoxidation with dimethyldioxirane, the 2',5'-bis-O-silyl derivatives of 9-(3-deoXy-beta-D-glyceropent-3-enofuranosyl)adenine gave the respective "3',4'-up" epoxides exclusively. Reaction between these epoxides and Me3Al was investigated in detail. It was found that the stereoselectivity of epoxide ring opening (anti versus syn) varied significantly upon changing the amount of Me3Al, the solvent, the O-silyl protecting group, and the reaction temperature. A possible reaction mechanism is proposed.

  DOI：

  10.1021/jo052243l
• 作为产物：
  描述：

  (3S,4S,5R)-5-(6-amino-9H-purin-9-yl)-4-((tert-butyldimethylsilyl)oxy)-2-(((tert-butyldimethylsilyl)oxy)methyl)-3-iodotetrahydrofuran-2-yl benzoate 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 甲醇 为溶剂， 以75%的产率得到9-[2,5-bis-O-(tert-butyldimethylsilyl)-3-deoxy-β-D-glyceropent-3-enofuranosyl]adenine
  参考文献：
  名称：

  Synthesis of 4′-benzoyloxycordycepin from adenosine

  摘要：

  With an aim to synthesize 4'-substituted cordycepins, the 4'-benzoyloxy precursor (9) was prepared from adenosine through an electrophilic addition (iodo-benzoyloxylation) to the 4',5'-unsaturated derivative (5) and subsequent radical-mediated removal of the 3'-iodine atom of the resulting adducts (6). Usefulness of 9 was briefly verified by synthesizing the 4'-allyl (12) and 4'-cyano (13) analogues of cordycepin. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2008.01.018

文献信息

• Synthesis and anti-HIV-1 evaluation of phosphonates which mimic the 5′-monophosphate of 4′-branched 2′,3′-didehydro-2′,3′-dideoxy nucleosides
  作者：Yutaka Kubota、Nobuhide Ishizaki、Kazuhiro Haraguchi、Takayuki Hamasaki、Masanori Baba、Hiromichi Tanaka

  DOI：10.1016/j.bmc.2010.08.037

  日期：2010.10.15

  Synthesis of the 4′-ethynyl and 4′-cyano phosphonates 8–11, which mimic the 5′-monophosphate of 4′-branched 2′,3′-didehydro-2′,3′-dideoxy nucleosides, was investigated by employing the 3′,4′-unsaturated nucleosides (13 and 28) as the starting material. The synthesis was initiated by the electrophilic addition of NIS/(EtO)2P(O)CH2OH to these unsaturated nucleosides. After introduction of the 2′,3′-double

  4'-乙炔基和4'-氰基的合成膦酸酯8 - 11，其模拟4'-支链2'，3'-二脱氢-2'，3'-二脱氧核苷，通过采用所研究的5'-单磷酸3′，4′-不饱和核苷（13和28）作为起始原料。合成是通过将NIS /（EtO）2 P（O）CH 2 OH亲电加至这些不饱和核苷而开始的。引入2'，3'-双键后，所得加合物的4'-羟甲基被转化为乙炔基或氰基。尽管4'-氰基膦酸酯9和11不够稳定，无法分离，但4'-乙炔基对应物（获得了8和10）的单铵盐。腺嘌呤衍生物8显示出几乎与d4T相当的抗HIV-1活性。
• Solvent Effect Observed in Nucleophilic Substitution of 4′-(Benzoyloxy)cordycepin with AlMe₃: Stereochemical Evidence for S_Ni Mechanism
  作者：Yutaka Kubota、Mayumi Kunikata、Kazuhiro Haraguchi、Hiromichi Tanaka

  DOI：10.1021/jo900289h

  日期：2009.5.1

  Nucleophilic substitution between the 4′-benzoyloxy derivative of cordycepin (3′-deoxyadenosine) and AlMe3 proceeds mostly with retention of configuration at the 4′-position: the 4′-benzoyloxy substrate having the β-d-configuration (8a) gave the 4′-methylated β-d-nucleoside (9a) with a high diastereomeric excess, while the substrate 8b having the opposite 4′-configuration gave the corresponding α-l-isomer

  虫草素（3'-脱氧腺苷）的4'-苯甲酰氧基衍生物和AlMe 3之间的亲核取代主要是保留了4'-位置的构型：具有β- d-构型（8a）的4'-苯甲酰氧基底物具有高的非对映异构体过量的4'-甲基化的β- d-核苷（9a），而具有相反的4'-构型的底物8b给出了具有相对较低的立体选择性的相应的α- 1-异构体（9b）。对此反应提出了S N i机理（从8到9）。溶剂的极性对立体选择性有重要影响，尤其是对于9b的形成。
• Phenylsulfanylation of 3′,4′-Unsaturated Adenosine Employing Thiophenol-<i>N</i>-Iodosuccinimide Leads to 4′-Phenylsulfanylcordycepin: Synthesis of 4′-Substituted Cordycepins on the Basis of Substitution of the Phenylsulfanyl Leaving Group
  作者：Yutaka Kubota、Mariko Ehara、Kazuhiro Haraguchi、Hiromichi Tanaka

  DOI：10.1021/jo201246y

  日期：2011.11.4

  Upon reaction of the 3',4'-unsaturated adenosine derivative 2 with N-iodosuccinimide (NIS) and thiophenol, an unexpected electrophilic hydrophenylsulfanylation proceeded to provide 4'-phenylsulfanylcordycepin 7 in 79% yield with the ratio 7a/7b = 6.6/1. A study of the reaction mechanism revealed that hydrogen iodide (HI) generated from NIS and PhSH acted as an active species. On the basis of a deuterium experiment using PhSD, initial protonation occurred at the beta face of the double bond to furnish the beta-pi complex III, which underwent anti addition of PhSH as a major pathway. Nucleophilic substitution of N-6-pivaloylated 9 with various alcohols in the presence of N-bromosuccinimide (NBS) gave the respective 4'-alpha-alkoxycordycepins 15a-21a as the major stereoisomers. Use of DAST in place of an alcohol gave the 4'-alpha-fluoro analogue 23a stereoselectively. Radical-mediated carbon carbon bond construction was also applicable to 7, giving 4'-alpha-allylcordycepin (24a) and 4'-alpha-cyanoethylcordycepin (25) derivatives.
• Anti versus Syn Opening of Epoxides Derived from 9-(3-Deoxy-β-<scp>d</scp>-<i>g</i><i>lycero</i>-pent-3-enofuranosyl)adenine with Me₃Al:  Factors Controlling the Stereoselectivity
  作者：Yutaka Kubota、Kazuhiro Haraguchi、Mayumi Kunikata、Mari Hayashi、Masaomi Ohkawa、Hiromichi Tanaka

  DOI：10.1021/jo052243l

  日期：2006.2.1

  [graphics]Upon epoxidation with dimethyldioxirane, the 2',5'-bis-O-silyl derivatives of 9-(3-deoXy-beta-D-glyceropent-3-enofuranosyl)adenine gave the respective "3',4'-up" epoxides exclusively. Reaction between these epoxides and Me3Al was investigated in detail. It was found that the stereoselectivity of epoxide ring opening (anti versus syn) varied significantly upon changing the amount of Me3Al, the solvent, the O-silyl protecting group, and the reaction temperature. A possible reaction mechanism is proposed.
• Synthesis of 4′-benzoyloxycordycepin from adenosine
  作者：Yutaka Kubota、Mayumi Kunikata、Nobuhide Ishizaki、Kazuhiro Haraguchi、Yuki Odanaka、Hiromichi Tanaka

  DOI：10.1016/j.tet.2008.01.018

  日期：2008.3

  With an aim to synthesize 4'-substituted cordycepins, the 4'-benzoyloxy precursor (9) was prepared from adenosine through an electrophilic addition (iodo-benzoyloxylation) to the 4',5'-unsaturated derivative (5) and subsequent radical-mediated removal of the 3'-iodine atom of the resulting adducts (6). Usefulness of 9 was briefly verified by synthesizing the 4'-allyl (12) and 4'-cyano (13) analogues of cordycepin. (C) 2008 Elsevier Ltd. All rights reserved.