acetic acid 4-chloromethyl-4-hydroxy-2-methoxy-3-[2-methyl-3-(3-methylbut-2-enyl)oxiranyl]cyclohexyl ester | 654055-67-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: acetic acid 4-chloromethyl-4-hydroxy-2-methoxy-3-[2-methyl-3-(3-methylbut-2-enyl)oxiranyl]cyclohexyl ester
• CAS: 654055-67-1
• 化学式: C₁₈H₂₉ClO₅
• 分子量: 360.878
• InChiKey: DBJNEIQABVYATC-WJQMWINMSA-N

物化性质

• 沸点：
  445.4±45.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.83
• 重原子数：
  24.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  68.29
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  acetic acid 4-chloromethyl-4-hydroxy-2-methoxy-3-[2-methyl-3-(3-methylbut-2-enyl)oxiranyl]cyclohexyl ester 在 4-二甲氨基吡啶 、 正丁基锂 、 potassium tert-butylate 、 六氯化钨 、 potassium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.42h， 生成 [(3R,4S,5S,6R)-5-methoxy-4-[(2E)-6-methylhepta-2,5-dien-2-yl]-1-oxaspiro[2.5]octan-6-yl] (E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoate
  参考文献：
  名称：

  Design, synthesis and evaluation of a series of novel fumagillin analogues

  摘要：

  A series of fumagillin analogues targeted at understanding tolerability of MetAP2 toward substitution at C4 and C6 were synthesized. Initially, the C6 side chain was maintained as cinnamoyl ester and C4 was modified. It was concluded that replacing the natural C4 of fumagillin with a benzyl oxime at C4 resulted in moderate loss of activity toward binding to MetAP2. Placement of a primary or secondary carbamate at C6 did not improve the potency of compounds toward inhibition of MetAP2. However, the inhibitory activity against MetAP2 was gained back by placing polar groups such as piperazinyl carbamate at C6. Small alkyl substituents on the amine of piperazinyl carbamate were well tolerated. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.08.031
• 作为产物：
  描述：

  5-甲氧基-4-[2-甲基-3-(3-甲基丁-2-烯基)环氧乙烷-2-基]-1-氧杂螺[2.5]辛烷-6-醇 在 4-二甲氨基吡啶 、 溶剂黄146 、 lithium chloride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 16.0h， 生成 acetic acid 4-chloromethyl-4-hydroxy-2-methoxy-3-[2-methyl-3-(3-methylbut-2-enyl)oxiranyl]cyclohexyl ester
  参考文献：
  名称：

  Design, synthesis and evaluation of a series of novel fumagillin analogues

  摘要：

  A series of fumagillin analogues targeted at understanding tolerability of MetAP2 toward substitution at C4 and C6 were synthesized. Initially, the C6 side chain was maintained as cinnamoyl ester and C4 was modified. It was concluded that replacing the natural C4 of fumagillin with a benzyl oxime at C4 resulted in moderate loss of activity toward binding to MetAP2. Placement of a primary or secondary carbamate at C6 did not improve the potency of compounds toward inhibition of MetAP2. However, the inhibitory activity against MetAP2 was gained back by placing polar groups such as piperazinyl carbamate at C6. Small alkyl substituents on the amine of piperazinyl carbamate were well tolerated. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.08.031

文献信息

• Investigation of novel fumagillin analogues as angiogenesis inhibitors
  作者：Hyung-Jung Pyun、Maria Fardis、James Tario、Cheng Y. Yang、Judy Ruckman、Dwight Henninger、Haolun Jin、Choung U. Kim

  DOI：10.1016/j.bmcl.2003.10.008

  日期：2004.1

  Modification of fumagillin was conducted to develop MetAP-2 inhibitors with desirable pharmacological properties. Replacement of the C4 side chain by benzyloxime preserves the inhibitory activity against MetAP-2 enzyme. Fumagillin analogues containing the C4 benzyloxime moiety were found to be very sensitive to the nature of the C6 substituent on the inhibition activity of HUVEC proliferation. This lack of correlation between MetAP-2 and HUVEC activities might be due to the cellular metabolism of the compounds by epoxide hydrolase, which is present in the cell. Compound (E)-3d, containing ethylpiperazinyl carbamate at C6 position, exhibited antiangiogenic effects similar to TNP-470 on matrigel plug assay and rat corneal micropocket assay. (C) 2003 Elsevier Ltd. All rights reserved.
• Fumarranol, a Rearranged Fumagillin Analogue That Inhibits Angiogenesis in Vivo
  作者：Jun Lu、Curtis R. Chong、Xiaoyi Hu、Jun O. Liu

  DOI：10.1021/jm060559v

  日期：2006.9.1

  The fumagillin family of natural products inhibits angiogenesis through the irreversible inhibition of the type 2 methionine aminopeptidase (MetAP2). Herein is reported a novel fumagillin analogue named fumarranol. It is shown that, like fumagillin, fumarranol selectively inhibits MetAP2 and endothelial cell proliferation. It is also active in a mouse model of angiogenesis in vivo. Unlike TNP-470, fumarranol does not covalently bind to MetAP2. Fumarranol may serve as a lead for a new class of angiogenesis inhibitors.