1-chloromethyl-3-methoxy-2-[2-methyl-3-(3-methylbut-2-enyl)oxiranyl]cyclohexane-1,4-diol | 135268-12-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-chloromethyl-3-methoxy-2-[2-methyl-3-(3-methylbut-2-enyl)oxiranyl]cyclohexane-1,4-diol
• 英文别名: 7-chloro-fumagillol
• CAS: 135268-12-1
• 化学式: C₁₆H₂₇ClO₄
• 分子量: 318.841
• InChiKey: IKABKKYGJWCZMB-JQOWZUPLSA-N

物化性质

• 沸点：
  435.9±45.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.26
• 重原子数：
  21.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  62.22
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  1-chloromethyl-3-methoxy-2-[2-methyl-3-(3-methylbut-2-enyl)oxiranyl]cyclohexane-1,4-diol 在 甲醇 、 4-二甲氨基吡啶 、 正丁基锂 、 4 A molecular sieve 、 六氯化钨 、 potassium carbonate 、 对甲苯磺酸 、 臭氧 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 生成 Ethanone,1-[(3R,4S,5S,6R)-6-hydroxy-5-methoxy-1-oxaspiro[2.5]oct-4-yl]-,O-(phenylmethyl)oxime, (1E)-
  参考文献：
  名称：

  Investigation of novel fumagillin analogues as angiogenesis inhibitors

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2003.10.008
• 作为产物：
  描述：

  烟曲霉素 在 溶剂黄146 、 lithium chloride 、 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 42.0h， 生成 1-chloromethyl-3-methoxy-2-[2-methyl-3-(3-methylbut-2-enyl)oxiranyl]cyclohexane-1,4-diol
  参考文献：
  名称：

  Synthesis and antiproliferative activity of ligerin and new fumagillin analogs against osteosarcoma

  摘要：

  Ligerin (1) is a natural chlorinated merosesquiterpenoid related to fumagillin (2) exhibiting a selective antiproliferative activity against osteosarcoma cell lines and an in vivo antitumor activity in a murine model. Semisynthesis of ligerin analogs was performed in order to study the effects of the C3-spiroepoxide substitution by a halogenated moiety together with the modulation of the C6 chain. Results showed that all derivatives exhibited an in vitro antiproliferative activity against osteosarcoma cell lines and that chlorohydrin compounds were equally or more active than their spiroepoxy analogs. Among semisynthetic analogs, the parent compound 1 was the best candidate for further studies since it exhibited higher or equivalent activity compared to TNP470 (3) against SaOS2 and MG63 human osteosarcoma cells with a four times weaker toxicity against HFF2 human fibroblasts. Quantitative videomicroscopy analysis was conducted and allowed a better understanding of the mechanism of its antiproliferative activity. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.04.012

文献信息

• Design, synthesis and evaluation of a series of novel fumagillin analogues
  作者：Maria Fardis、Hyung-Jung Pyun、James Tario、Haolun Jin、Choung U Kim、Judy Ruckman、Yun Lin、Louis Green、Brian Hicke

  DOI：10.1016/j.bmc.2003.08.031

  日期：2003.11

  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.