2-乙酰氧基甲基-2-羟甲基-1-亚甲基环丙烷 | 1026676-05-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 2-乙酰氧基甲基-2-羟甲基-1-亚甲基环丙烷
• 英文名称: 2-acetoxymethyl-2-hydroxymethyl-1-methylenecyclopropane
• 英文别名: [1-(Hydroxymethyl)-2-methylidenecyclopropyl]methyl acetate；[1-(hydroxymethyl)-2-methylidenecyclopropyl]methyl acetate
• CAS: 1026676-05-0
• 化学式: C₈H₁₂O₃
• 分子量: 156.181
• InChiKey: MQDKTGWWWUAEPE-UHFFFAOYSA-N

物化性质

• 沸点：
  209.4±15.0 °C(Predicted)
• 密度：
  1.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  11
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-乙酰氧基甲基-2-羟甲基-1-亚甲基环丙烷 在 吡啶 、 二乙胺基三氟化硫 作用下， 以 二氯甲烷 为溶剂， 以87%的产率得到3-乙酰氧基甲基-3-氟-1-亚甲基环丁烷
  参考文献：
  名称：

  Fluorinated methylenecyclopropane analogues of nucleosides. Synthesis and antiviral activity of (Z)- and (E)-9-{[(2-fluoromethyl-2-hydroxymethyl)-cyclopropylidene]methyl}adenine and -guanine

  摘要：

  Synthesis and antiviral activity of the title fluoromethylenecyclopropane analogues 15a, 15b, 16a, and 16b is described. Methylenecyclopropane carboxylate was first transformed to 2,2-bis-hydroxymethylmethylenecyclopropane. Selective monoacetylation followed by introduction of fluorine gave 2-acetoxymethyl-2-fluoromethylmethylenecyclopropane as the key inter-mediate. The synthesis of analogues 15a, 15b, 16a, and 16b then followed alkylation-elimination procedure as described previously for other methylenecyclopropane analogues. The adenine Z-isomer 15a was found to be a potent inhibitor of Epstein-Barr virus (EBV) in vitro with EC50/CC50 (mu M) 0.5/55.7. Compounds 15b, 16a, and 16b were also active but at higher concentrations, EC50/CC50 (mu M) 3.2-7.5/53.6-64.1. Analogue 15a inhibited hepatitis C virus by virtue of its cytotoxicity and it moderately inhibited replication of the Towne strain of human cytomegalovirus (HCMV). The E-isomer 16a was a substrate for adenosine deaminase, whereas the Z-isomer 15a was not deaminated. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.11.082
• 作为产物：
  描述：

  原乙酸三甲酯 、 2,2-bis(hydroxymethyl)methylenecyclopropane 在 对甲苯磺酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以78%的产率得到2-乙酰氧基甲基-2-羟甲基-1-亚甲基环丙烷
  参考文献：
  名称：

  Fluorinated methylenecyclopropane analogues of nucleosides. Synthesis and antiviral activity of (Z)- and (E)-9-{[(2-fluoromethyl-2-hydroxymethyl)-cyclopropylidene]methyl}adenine and -guanine

  摘要：

  Synthesis and antiviral activity of the title fluoromethylenecyclopropane analogues 15a, 15b, 16a, and 16b is described. Methylenecyclopropane carboxylate was first transformed to 2,2-bis-hydroxymethylmethylenecyclopropane. Selective monoacetylation followed by introduction of fluorine gave 2-acetoxymethyl-2-fluoromethylmethylenecyclopropane as the key inter-mediate. The synthesis of analogues 15a, 15b, 16a, and 16b then followed alkylation-elimination procedure as described previously for other methylenecyclopropane analogues. The adenine Z-isomer 15a was found to be a potent inhibitor of Epstein-Barr virus (EBV) in vitro with EC50/CC50 (mu M) 0.5/55.7. Compounds 15b, 16a, and 16b were also active but at higher concentrations, EC50/CC50 (mu M) 3.2-7.5/53.6-64.1. Analogue 15a inhibited hepatitis C virus by virtue of its cytotoxicity and it moderately inhibited replication of the Towne strain of human cytomegalovirus (HCMV). The E-isomer 16a was a substrate for adenosine deaminase, whereas the Z-isomer 15a was not deaminated. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.11.082

文献信息

• Phosphonate analogues of cyclopropavir phosphates and their E-isomers. Synthesis and antiviral activity
  作者：Santosh B. Mhaske、Bashar Ksebati、Mark N. Prichard、John C. Drach、Jiri Zemlicka

  DOI：10.1016/j.bmc.2009.04.020

  日期：2009.6

  Z- and E-Phosphonate analogues 12 and 13 derived from cyclopropavir and the corresponding cyclic phosphonates 14 and 15 were synthesized and their antiviral activity was investigated. The 2,2-bis(hydroxymethylmethylenecyclopropane acetate (17) was transformed to tetrahydropyranyl acetate 18. Deacetylation gave intermediate 19 which was converted to bromide 20. Alkylation with diisopropyl methylphosphonate afforded after protecting group exchange (21 to 22) acetylated phosphonate intermediate 22. Addition of bromine gave the dibromo derivative 16 which was used in the alkylation-elimination procedure with 2-amino-6-chloropurine to give Z- and E-isomers 23 and 24. Hydrolytic dechlorination coupled with removal of all protecting groups gave the guanine phosphonates 12 and 13. Cyclization afforded the cyclic phosphonates 14 and 15. Z-Phosphonate 12 was a potent and noncytotoxic inhibitor of human and murine cytomegalovirus (HCMV and MCMV) with EC50 2.2-2.7 and 0.13 mu M, respectively. It was also an effective agent against Epstein-Barr virus (EBV, EC50 3.1 mu M). The cyclic phosphonate 14 inhibited HCMV (EC50 2.4-11.5 mu M) and MCMV (EC50 0.4 mu M) but it was ineffective against EBV. Both phosphonates 12 and 14 were as active against two HCMV Towne strains with mutations in UL97 as they were against wild-type HCMV thereby circumventing resistance due to such mutations. Z-Phosphonate 12 was a moderate inhibitor of replication of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) but it was a potent agent against varicella zoster virus (VZV, EC50 2.9 mu M). The cyclic phosphonate 14 lacked significant potency against these viruses. E-isomers 13 and 15 were devoid of antiviral activity. (C) 2009 Elsevier Ltd. All rights reserved.