allyl 2-C-methyl-2,3-O-(1-methylethylidene)-α-D-ribofuranoside | 943638-39-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: allyl 2-C-methyl-2,3-O-(1-methylethylidene)-α-D-ribofuranoside
• 英文别名: [(3aR,4S,6R,6aR)-2,2,3a-trimethyl-4-prop-2-enoxy-6,6a-dihydro-4H-furo[3,4-d][1,3]dioxol-6-yl]methanol
• CAS: 943638-39-9
• 化学式: C₁₂H₂₀O₅
• 分子量: 244.288
• InChiKey: NHPNBTFSHAZTOA-MWGHHZFTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  57.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  allyl 2-C-methyl-2,3-O-(1-methylethylidene)-α-D-ribofuranoside 、 叔丁基二苯基氯硅烷 在 咪唑 、 1,3-bis[(diphenylphosphino)propane]dichloronickel(II) 、 二异丁基氢化铝 、 sodium tetrahydroborate 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 、 甲醇 为溶剂， 以82%的产率得到(1R)-2-[tert-butyl(diphenyl)silyl]oxy-1-[(4R,5S)-5-(hydroxymethyl)-2,2,5-trimethyl-1,3-dioxolan-4-yl]ethanol
  参考文献：
  名称：

  2'-β- C-甲基-neplanocin衍生物作为抗HCV剂的合成

  摘要：

  描述了2'-β- C-甲基-neplanocin衍生物的合成。关键中间体环戊烯基醇12由糖5以12个步骤制备。的耦合12与适当保护的嘌呤，通过Mitsunobu反应7-脱氮嘧啶，尿嘧啶和嘧啶碱基，接着脱保护得到目标环戊烯基核苷（18 - 23，27）。合成的化合物被评估为体外丙型肝炎病毒（HCV）的潜在抑制剂。不幸的是，它们都没有显示出低于EC 50 100μM的抗HCV活性。

  DOI：

  10.1016/j.tetlet.2008.04.115
• 作为产物：
  描述：

  allyl 2-C-methyl-α-D-ribofuranoside 、 2,2-二甲氧基丙烷 在 对甲苯磺酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 allyl 2-C-methyl-2,3-O-(1-methylethylidene)-α-D-ribofuranoside
  参考文献：
  名称：

  Synthesis and HCV inhibitory properties of 9-deaza- and 7,9-dideaza-7-oxa-2′-C-methyladenosine

  摘要：

  As a part of an ongoing medicinal chemistry effort to identify inhibitors of the Hepatitis C Virus RNA replication, we report here the synthesis and biological evaluation of 9-deaza- and 7,9-dideaza-7-oxa-2'-C-methyladenosine. The parent 2'-C-methyladenosine shows excellent intracellular inhibitory activity but poor pharmacokinetic profile. Replacement of the nucleoside-defining 9-N of 2'-C-methyladenosine with a carbon atom was designed to yield metabolically more stable C-nucleosides. Modifications at position 7 were designed to exploit the importance of the hydrogen bond accepting properties of this heteroatom in modulating the adenosine deaminase (ADA) mediated 6-N deamination. 7-Oxa-7,9-dideaza-2'-C-methyladenosine was found to be a moderately active inhibitor of intracellular HCV RNA replication, whereas 9-deaza- 2'-C-methyladenosine showed only weak activity despite excellent overlap of both of the synthesized target compounds with T-C-methyladenosine's three dimensional structure. Position 7 of the nucleobase proved to be an effective handle for modulating ADA-mediated degradation, with the rate of degradation correlating with the hydrogen-bonding properties at this position. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.05.020

文献信息

• Synthesis of 2′-β-C-methyl-neplanocin derivatives as anti-HCV agents
  作者：Xibin Liao、Gabor Butora、David B. Olsen、Steven S. Carroll、Daniel R. McMasters、Joseph F. Leone、Mark Stahlhut、George A. Doss、Lihu Yang、Malcolm MacCoss

  DOI：10.1016/j.tetlet.2008.04.115

  日期：2008.6

  The synthesis of 2′-β-C-methyl-neplanocin derivatives is described. The key intermediate cyclopentenyl alcohol 12 is prepared from sugar 5 in 12 steps. Coupling of 12 with appropriately protected purine, 7-deaza pyrimidine, uracil and pyrimidine bases via the Mitsunobu reaction followed by deprotection afforded the target cyclopentenyl nucleosides (18–23, 27). The synthesized compounds were evaluated

  描述了2'-β- C-甲基-neplanocin衍生物的合成。关键中间体环戊烯基醇12由糖5以12个步骤制备。的耦合12与适当保护的嘌呤，通过Mitsunobu反应7-脱氮嘧啶，尿嘧啶和嘧啶碱基，接着脱保护得到目标环戊烯基核苷（18 - 23，27）。合成的化合物被评估为体外丙型肝炎病毒（HCV）的潜在抑制剂。不幸的是，它们都没有显示出低于EC 50 100μM的抗HCV活性。
• Synthesis and HCV inhibitory properties of 9-deaza- and 7,9-dideaza-7-oxa-2′-C-methyladenosine
  作者：Gabor Butora、David B. Olsen、Steven S. Carroll、Daniel R. McMasters、Christoph Schmitt、Joseph F. Leone、Mark Stahlhut、Christine Burlein、Malcolm MacCoss

  DOI：10.1016/j.bmc.2007.05.020

  日期：2007.8

  As a part of an ongoing medicinal chemistry effort to identify inhibitors of the Hepatitis C Virus RNA replication, we report here the synthesis and biological evaluation of 9-deaza- and 7,9-dideaza-7-oxa-2'-C-methyladenosine. The parent 2'-C-methyladenosine shows excellent intracellular inhibitory activity but poor pharmacokinetic profile. Replacement of the nucleoside-defining 9-N of 2'-C-methyladenosine with a carbon atom was designed to yield metabolically more stable C-nucleosides. Modifications at position 7 were designed to exploit the importance of the hydrogen bond accepting properties of this heteroatom in modulating the adenosine deaminase (ADA) mediated 6-N deamination. 7-Oxa-7,9-dideaza-2'-C-methyladenosine was found to be a moderately active inhibitor of intracellular HCV RNA replication, whereas 9-deaza- 2'-C-methyladenosine showed only weak activity despite excellent overlap of both of the synthesized target compounds with T-C-methyladenosine's three dimensional structure. Position 7 of the nucleobase proved to be an effective handle for modulating ADA-mediated degradation, with the rate of degradation correlating with the hydrogen-bonding properties at this position. (c) 2007 Elsevier Ltd. All rights reserved.