2,2-bis(acetoxymethyl)methylenecyclopropane | 632325-60-1

• 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
• 英文名称: 2,2-bis(acetoxymethyl)methylenecyclopropane
• 英文别名: [1-(Acetyloxymethyl)-2-methylidenecyclopropyl]methyl acetate
• CAS: 632325-60-1
• 化学式: C₁₀H₁₄O₄
• 分子量: 198.219
• InChiKey: OMICDMZRVSEYJO-UHFFFAOYSA-N

物化性质

• 沸点：
  232.2±13.0 °C(Predicted)
• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  14
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,2-bis(acetoxymethyl)methylenecyclopropane 在 氨 、 溴 、 potassium carbonate 作用下， 以 甲醇 、 四氯化碳 、 N,N-二甲基甲酰胺 为溶剂， 反应 33.0h， 生成 cyclopropavir
  参考文献：
  名称：

  Synthesis and Antiviral Activity of (Z)- and (E)-2,2-[Bis(hydroxymethyl)cyclopropylidene]methylpurines and -pyrimidines:  Second-Generation Methylenecyclopropane Analogues of Nucleosides

  摘要：

  The second generation of methylenecyclopropane analogues of nucleosides 5a-5i and 6a-6i was synthesized and evaluated for antiviral activity. The 2,2-bis(hydroxymethyl)methylenecyclopropane (11) was converted to dibromo derivative 7 via acetate 12. Alkylation-elimination of adenine (16) with 7 afforded the Z/E mixture of acetates 17 + 18, which was deacetylated to give analogues 5a and 6a separated by chromatography. A similar reaction with 2-amino-6-chloropurine (19) afforded acetates 20 + 21 and, after deprotection and separation, isomers 5f and 6f. The latter served as starting materials for synthesis of analogues 5b, 5e, 5g-5i and 6b, 6e, 6g-6i. Alkylation-elimination of N(4)-acetylcytosine (22) with 7 afforded a mixture of isomers 5c + 6c which were separated via N(4)-benzoyl derivatives 23 and 24. Deprotection furnished analogues 5c and 6c. Alkylation of 2,4-bis(trimethylsilyloxy)-5-methylpyrimidine (25) with 7 led to bromo derivative 26. Elimination of HBr followed by deacetylation and separation gave thymine analogues 5d and 6d. The guanine Z-isomer 5b was the most effective against human and murine cytomegalovirus (HCMV and MCMV) with EC(50) = 0.27-0.49 muM and no cytotoxicity. The 6-methoxy analogue 5g was also active (EC(50) = 2.0-3.5 muM) whereas adenine Z-isomer 5a was less potent (EC(50) = 3.6-11.7 muM). Cytosine analogue 5c was moderately effective, but 2-amino-6-cyclopropylamino derivative 5e was inactive. All E-isomers were devoid of anti-CMV activity, and none of the analogues was significantly active against herpes simplex viruses (HSV-1 or HSV-2). The potency against Epstein-Barr virus (EBV) was assay-dependent. In Daudi cells, the E-isomers of 2-amino-6-cyclopropylamino- and 2,6-diaminopurine derivatives 6e and 6h were the most potent (EC(50) approximate to 0.3 muM), whereas only the thymine Z-isomer 5d was active (EC(50) = 4.6 muM). Guanine Z-derivative 5b was the most effective compound in H-1 cells (EC(50) = 7 muM). In the Z-series, the 2-amino-6-methoxypurine analogue 5g was the most effective against varicella zoster virus (VZV, EC(50) = 3.3 muM) and 2,6-diaminopurine 5h against hepatitis B virus (HBV, EC(50) = 4 muM). Adenine analogues 5a and 6a were moderately active as substrates for adenosine deaminase.

  DOI：

  10.1021/jm030316s
• 作为产物：
  描述：

  2-碘甲基环丙烷-1,1-二羧酸二乙酯 在 吡啶 、 lithium aluminium tetrahydride 、 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 31.0h， 生成 2,2-bis(acetoxymethyl)methylenecyclopropane
  参考文献：
  名称：

  基于双活性嘧啶的碳环核苷衍生物：合成，以及计算机和体外抗糖尿病和抗微生物研究

  摘要：

  糖尿病 （DM） 是一种慢性代谢紊乱，其特征是高血糖水平，损害体内葡萄糖的产生。在过去的几十年里，它的患病率稳步上升，导致免疫力下降和对微生物感染的易感性增加。与糖尿病相关的免疫功能障碍会增加脆弱性，而神经病变会使四肢的感觉迟钝，从而降低受伤意识。因此，开发用于抗糖尿病和抗感染治疗的新型化合物对于减轻不良反应势在必行。在这项研究中，我们设计并合成了具有 C-4 取代的基于嘧啶的碳环核苷衍生物，以评估它们在抑制 α-葡萄糖苷酶治疗糖尿病 （DM） 和微生物感染方面的潜力。化合物 8b 和 10a 对 α-葡萄糖苷酶 （分别为 43.292 nmol 和 48.638 nmol） 和值得注意的对接能量 （分别为 -9.4 kcal mol-1 和 -10.3 kcal mol-1） 显示出有希望的 IC50 值。此外，化合物 10a 和 10b 对蜡样芽孢杆菌表现出更好的抗菌活性，在 100 μl

  DOI：

  10.1039/d4ra00304g

文献信息

• 2,2-bis-(hydroxymethyl)cyclopropylidenemethyl-purines and pyrmindines as antiviral agents
  申请人：Zemlicka Jiri

  公开号：US20050113393A1

  公开（公告）日：2005-05-26

  Compounds which are active against viruses have the following formulas: wherein B is a purine or pyrimidine heterocyclic ring or base. In a preferred embodiment, the purine include 6-aminopurine (adenine), 6-hydroxypurine (hypoxanthine), 2-amino-6-hydroxypurine (guanine), 2,6-diamino-purine, 2-amino-6-azidopurine, 2-amino-6-halo substituted purines such as 2-amino-6-chloropurine, 2-amino-6-fluoropurine, 2-amino-6-alkoxypurines such as 2-amino-6-methoxypurine, 2-amino-6-cyclopropylaminopurine, 2-amino-6-alkylamino or 2-amino-6-dialkylamino substituted purines, 2-amino-6-thiopurine, 2-amino-6-alkylthio substituted purines, 3-deazapurines, 7-deazapurines and 8-azapurines. The pyrimidine incorporates cytosine, uracil and thymine, 5-halo substituted cytosines and uracils, 5-alkyl substituted cytosines and uracils including derivatives with a saturated or unsaturated alkyl group and 6-azapyrimidines.

  具有抗病毒活性的化合物具有以下公式：其中B是嘌呤或嘧啶杂环环或碱基。在一个首选实施例中，嘌呤包括6-氨基嘌呤（腺嘌呤）、6-羟基嘌呤（次黄嘌呤）、2-氨基-6-羟基嘌呤（鸟嘌呤）、2,6-二氨基嘌呤，2-氨基-6-叠氮基嘌呤，2-氨基-6-卤代嘌呤，例如2-氨基-6-氯嘌呤，2-氨基-6-氟嘌呤，2-氨基-6-烷氧基嘌呤，例如2-氨基-6-甲氧基嘌呤，2-氨基-6-环丙基氨基嘌呤，2-氨基-6-烷基氨基或2-氨基-6-二烷基氨基嘌呤，2-氨基-6-硫嘌呤，2-氨基-6-烷硫代嘌呤，3-脱氮嘌呤，7-脱氮嘌呤和8-氮嘌呤。嘧啶包括胞嘧啶、尿嘧啶和胸腺嘧啶，5-卤代胞嘧啶和尿嘧啶，5-烷基代胞嘧啶和尿嘧啶，包括具有饱和或不饱和烷基基团的衍生物和6-氮杂嘧啶。
• 2,2-Bis-(hydroxymethyl)cyclopropylidenemethyl-Purines and -Pyrimidines As Antiviral Agents
  申请人：Zemlicka Jiri

  公开号：US20090118308A1

  公开（公告）日：2009-05-07

  Compounds which are active against viruses have the following formulas: wherein B is a purine or pyrimidine heterocyclic ring or base. In a preferred embodiment, the purine include 6-aminopurine (adenine), 6-hydroxypurine (hypoxanthine), 2-amino-6-hydroxypurine (guanine), 2,6-diamino-purine, 2-amino-6-azidopurine, 2-amino-6-halo substituted purines such as 2-amino-6-chloropurine, 2-amino-6-fluoropurine, 2-amino-6-alkoxypurines such as 2-amino-6-methoxypurine, 2-amino-6-cyclopropylaminopurine, 2-amino-6-alkylamino or 2-amino-6-dialkylamino substituted purines, 2-amino-6-thiopurine, 2-amino-6-alkylthio substituted purines, 3-deazapurines, 7-deazapurines and 8-azapurines. The pyrimidine incorporates cytosine, uracil and thymine, 5-halo substituted cytosines and uracils, 5-alkyl substituted cytosines and uracils including derivatives with a saturated or unsaturated alkyl group and 6-azapyrimidines.

  对病毒具有活性的化合物具有以下公式：其中B是嘌呤或嘧啶杂环环或碱基。在优选实施例中，嘌呤包括6-氨基嘌呤（腺嘌呤），6-羟基嘌呤（次黄嘌呤），2-氨基-6-羟基嘌呤（鸟嘌呤），2,6-二氨基嘌呤，2-氨基-6-叠氮基嘌呤，2-氨基-6-卤代嘌呤，例如2-氨基-6-氯嘌呤，2-氨基-6-氟嘌呤，2-氨基-6-烷氧基嘌呤，例如2-氨基-6-甲氧基嘌呤，2-氨基-6-环丙基氨基嘌呤，2-氨基-6-烷基氨基或2-氨基-6-二烷基氨基取代的嘌呤，2-氨基-6-硫代嘌呤，2-氨基-6-烷基硫代取代嘌呤，3-去氮嘌呤，7-去氮嘌呤和8-氮杂嘧啶。嘧啶包括胞嘧啶，尿嘧啶和胸腺嘧啶，5-卤代胞嘧啶和尿嘧啶，5-烷基取代的胞嘧啶和尿嘧啶，包括具有饱和或不饱和烷基的衍生物和6-氮杂嘧啶。
• 2,2-BIS-(HYDROXYMETHYL)CYCLOPROPYLIDENEMETHYL-PURINES AND -PYRIMIDINES AS ANTIVIRAL AGENTS
  申请人：Zemlicka Jiri

  公开号：US20110275652A1

  公开（公告）日：2011-11-10

  Compounds which are active against viruses have the following formulas: wherein B is a purine or pyrimidine heterocyclic ring or base. In a preferred embodiment, the purine include 6-aminopurine (adenine), 6-hydroxypurine (hypoxanthine), 2-amino-6-hydroxypurine (guanine), 2,6-diamino-purine, 2-amino-6-azidopurine, 2-amino-6-halo substituted purines such as 2-amino-6-chloropurine, 2-amino-6-fluoropurine, 2-amino-6-alkoxypurines such as 2-amino-6-methoxypurine, 2-amino-6-cyclopropylaminopurine, 2-amino-6-alkylamino or 2-amino-6-dialkylamino substituted purines, 2-amino-6-thiopurine, 2-amino-6-alkylthio substituted purines, 3-deazapurines, 7-deazapurines and 8-azapurines. The pyrimidine incorporates cytosine, uracil and thymine, 5-halo substituted cytosines and uracils, 5-alkyl substituted cytosines and uracils including derivatives with a saturated or unsaturated alkyl group and 6-azapyrimidines.

  具有抗病毒活性的化合物具有以下公式：其中B是一种嘌呤或嘧啶杂环环或碱基。在优选实施例中，嘌呤包括6-氨基嘌呤（腺嘌呤）、6-羟基嘌呤（次黄嘌呤）、2-氨基-6-羟基嘌呤（鸟嘌呤）、2,6-二氨基嘌呤、2-氨基-6-叠氮基嘌呤、2-氨基-6-卤代嘌呤，例如2-氨基-6-氯嘌呤、2-氨基-6-氟嘌呤、2-氨基-6-烷氧基嘌呤，例如2-氨基-6-甲氧基嘌呤、2-氨基-6-环丙胺基嘌呤、2-氨基-6-烷基氨基或2-氨基-6-二烷基氨基取代的嘌呤，2-氨基-6-硫代嘌呤，2-氨基-6-烷基硫代取代的嘌呤，3-脱氮嘌呤，7-脱氮嘌呤和8-氮杂嘧啶。嘧啶包括胞嘧啶、尿嘧啶和胸腺嘧啶，5-卤代胞嘧啶和尿嘧啶，5-烷基取代的胞嘧啶和尿嘧啶，包括具有饱和或不饱和烷基的衍生物和6-氮杂嘧啶。
• Nucleotides and Pronucleotides of 2,2-Bis(hydroxymethyl)methylenecyclopropane Analogues of Purine Nucleosides:  Synthesis and Antiviral Activity
  作者：Zhaohua Yan、Earl R. Kern、Elizabeth Gullen、Yung-Chi Cheng、John C. Drach、Jiri Zemlicka

  DOI：10.1021/jm040149b

  日期：2005.1.1

  Phenylmethylphosphor-L-alaninate pronucleotides 7a, 7b, 8a, and 8b, cyclic phosphates 10a and 10b, and phosphates 11a and 11b derived from 2,2-bis(hydroxymethyl)methylenecyclopropane analogues 1a, 1b, 2a, and 2b were synthesized and evaluated for their antiviral activity. An improved protocol for the synthesis of analogues 1a, 1b, 2a, and 2b is also described. Phosphate 11a was the most effective agent against human and murine cytomegalovirus (EC50 0.25-1.1 muM). The Z-pronucleotides 7a and 7b had EC50 3.6-25.2 and 3-18.4 muM, respectively. The EC50 of cyclic phosphate 10a was 6.0-20 muM. The activity against Epstein-Barr (EBV) was assay-dependent. Pronucleotides 7a and 7b and phosphate 11a had EC50 2.3-3.4 muM against EBV/H-1, but 7b was cytotoxic (CC50 3.8 muM). Cyclic phosphate 10a was the only compound effective against EBV/Daudi (EC50 0.96 muM). but it was inactive in H-1 cells. Pronucleotide 7a was active against varicella zoster virus with EC50 6.3 and 7.3 muM, respectively. and hepatitis B virus (HBV, EC50 4.1 muM). Cyclic phosphate 10a was the most effective analogue against HBV (EC50 0.8 muM).
• WO2019172835A5
  申请人：——

  公开号：WO2019172835A5

  公开（公告）日：2022-03-16