(-)-4',5'-dihydrofumagillol | 94300-56-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (-)-4',5'-dihydrofumagillol
• 英文别名: (3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbutyl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-ol
• CAS: 94300-56-8
• 化学式: C₁₆H₂₈O₄
• 分子量: 284.396
• InChiKey: JGCRLPHPOGVOJE-JQOWZUPLSA-N

物化性质

• 沸点：
  385.4±42.0 °C(Predicted)
• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  54.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-甲氧基肉桂酸 、 (-)-4',5'-dihydrofumagillol 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 48.0h， 生成 p-methoxycinnamic acid (3R,4S,5S,6R)-5-methoxy-4-[(1R,2R)-1,2-epoxy-1,5-dimethylhexyl]-1-oxaspiro[2.5]oct-6-yl ester 、 [(3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbutyl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-yl] (E)-3-(4-methoxyphenyl)prop-2-enoate
  参考文献：
  名称：

  MetAP-2 Inhibitors Based on the Fumagillin Structure. Side-Chain Modification and Ring-Substituted Analogues

  摘要：

  The preparation of a series of new fumagillin-derived MetAP-2 inhibitors is described. The synthetic approach was designed so as to permit modification of the fumagillin backbone at sites inaccessible through semisynthesis or previously existing total syntheses. An Evans aldolization and a ring-closing metathesis allowed the preparation of a pivotal intermediate which could then be functionalized in various ways using already established or newly developed methodologies.

  DOI：

  10.1021/jo035065+
• 作为产物：
  描述：

  (E)-4-tert-butyldimethylsilyloxy-1-iodo-2-methyl-1-butene 在 镍 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 chromium(VI) oxide 、 正丁基锂 、 草酰氯 、 硫酸 、 四丁基氟化铵 、 三甲基铝 、 sodium hydride 、 碳酸氢钠 、 四丁基高碘酸铵 、 magnesium 、 N,N-二甲基甲酰胺 、 间氯过氧苯甲酸 、 2,3-二氯-5,6-二氰基-1,4-苯醌 、 silver(l) oxide 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醚 、 正己烷 、 二氯甲烷 、 氯仿 、 水 、 二甲基亚砜 、 丙酮 、 甲苯 为溶剂， 反应 79.0h， 生成 (-)-4',5'-dihydrofumagillol
  参考文献：
  名称：

  MetAP-2 Inhibitors Based on the Fumagillin Structure. Side-Chain Modification and Ring-Substituted Analogues

  摘要：

  The preparation of a series of new fumagillin-derived MetAP-2 inhibitors is described. The synthetic approach was designed so as to permit modification of the fumagillin backbone at sites inaccessible through semisynthesis or previously existing total syntheses. An Evans aldolization and a ring-closing metathesis allowed the preparation of a pivotal intermediate which could then be functionalized in various ways using already established or newly developed methodologies.

  DOI：

  10.1021/jo035065+

文献信息

• Fumigillol compounds and methods of making and using same
  申请人：Zafgen, Inc.

  公开号：US10220015B2

  公开（公告）日：2019-03-05

  The disclosure provides fumagillol type compounds and their use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of using, e.g. in the treatment of obesity are provided.

  本公开提供了烟曲霉素类化合物及其在治疗肥胖症等疾病中的用途。提供了药物组合物和使用方法，例如治疗肥胖症的方法。
• Treatment for tumors driven by metabolic dysfunction
  申请人：SynDevRx, Inc.

  公开号：US10646463B2

  公开（公告）日：2020-05-12

  The present disclosure relates to modified or polymer conjugated MetAP2 inhibitors. The present disclosure also relates to methods of treating metabolically-driven diseases and disorders, such as certain cancers.

  本公开涉及修饰的或聚合物共轭的 MetAP2 抑制剂。本公开还涉及治疗代谢驱动的疾病和失调（如某些癌症）的方法。
• FUMIGILLOL COMPOUNDS AND METHODS OF MAKING AND USING SAME
  申请人：Zafgen, Inc.

  公开号：US20150126489A1

  公开（公告）日：2015-05-07

  The disclosure provides fumagillol type compounds and their use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of using, e.g. in the treatment of obesity are provided.
• TREATMENT FOR TUMORS DRIVEN BY METABOLIC DYSFUNCTION
  申请人：SynDevRx, Inc.

  公开号：US20170196830A1

  公开（公告）日：2017-07-13

  The present disclosure relates to modified or polymer conjugated MetAP2 inhibitors. The present disclosure also relates to methods of treating metabolically-driven diseases and disorders, such as certain cancers.
• BIOMARKERS OF METAP2 INHIBITORS AND APPLICATIONS THEREOF
  申请人：SynDevRx, Inc.

  公开号：US20200129457A1

  公开（公告）日：2020-04-30

  The present disclosure relates to small molecule or polymer conjugated MetAP2 inhibitors. The present disclosure also relates to methods of treating, or ameliorating at least one symptom of metabolic dysfunction associated with a treatment in a subject having a disease, such as cancer. The present disclosure also relates to methods of treating, or ameliorating at least one symptom of cancer comprising administering a combination of a polymer conjugated MetAP2 inhibitors and at least one second agent wherein the second agent may induce metabolic dysfunction.