6-oxo-6-deoxyfumagillol | 132746-88-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-oxo-6-deoxyfumagillol
• 英文别名: RK-805；Fumaginone；fumigilone；5-Dehydrofumagillol；(3R,4S,5S)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-one
• CAS: 132746-88-4
• 化学式: C₁₆H₂₄O₄
• 分子量: 280.364
• InChiKey: RKYFKXLMWVUYJY-SUJAAXHWSA-N

物化性质

• 沸点：
  388.0±42.0 °C(Predicted)
• 密度：
  1.13±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  51.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-oxo-6-deoxyfumagillol 在 lithium hexamethyldisilazane 、 N-氟代双苯磺酰胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.67h， 以44.7%的产率得到SH-R01-A-9
  参考文献：
  名称：

  [EN] OXASPIRO [2.5] OCTANE DERIVATIVES AND ANALOGS
  [FR] DÉRIVÉS D'OXASPIRO[2.5]OCTANE ET ANALOGUES

  摘要：

  这项发明提供了氧杂螺[2.5]辛烷衍生物和类似物，其制备方法，中间体，药物组合物以及在治疗各种疾病和状况中的用途，例如超重和肥胖。

  公开号：

  WO2012122264A1
• 作为产物：
  描述：

  烟曲霉素 在 sodium hydroxide 、 4 A molecular sieve 、 pyridinium chlorochromate 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 3.5h， 生成 6-oxo-6-deoxyfumagillol
  参考文献：
  名称：

  RK-805, an endothelial-cell-growth inhibitor produced by Neosartorya sp., and a docking model with methionine aminopeptidase-2

  摘要：

  We found that a fungus Neosartorya sp. produced an angiogenesis inhibitor, RK-805. By spectroscopic analyses and semisynthetic methods from fumagillin, the structure of RK-805 was identified as 6-oxo-6-deoxyfumagillol, which has not been reported as a natural product. RK-805 preferentially inhibited the growth of human umbilical vein endothelial cells (HUVECs) rather than that of human normal fibroblast in cell proliferation assays and blocked endothelial cell migration induced by vascular endothelial growth factor (VEGF). Moreover, RK-805 selectively inhibited methionine aminopeptidase-2 (MetAP2), but not methionine aminopeptidase-1 (MetAP1). The docked structure of RK-805 complexed with human MetAP2 indicated that not only a covalent bond between a nucleophilic imidazole nitrogen atom of His231 and the carbon of the reactive spirocyclic epoxide of RK-805, but also a hydrogen bond between NH (Asn329) and the carbonyl group of RK-805 at C-6 promote close contact in the binding pocket of the enzyme. Taken together, these results suggest that structure activity relationships of RK-805 derivatives at both C-4 and C-6, in comparison with ovalicin and TNP-470, would be useful for development of new angiogenesis inhibitors. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2003.09.104

文献信息

• Chemical Modification of Fumagillin. II. 6-Amino-6-deoxyfumagillol and Its Derivatives.
  作者：Shogo MARUI、Shoji KISIMOTO

  DOI：10.1248/cpb.40.575

  日期：——

  6-Amino-6-deoxyfumagillol (5) was synthesized by reductive amination of 6-oxo-6-deoxyfumagillol (4), which was obtained by oxidation of fumagiollol (2). The reduction proceeded stereoselectively by the equatorial attack of hydride and 5 was found to have the same stereochemistry as that of 2. Several derivatives of 5 were prepared and most of them showed anti-angiogenic activity comparable to that of fumagillol derivatives.

  6-氨基-6-去氧富马吉洛尔（5）是通过对6-氧-6-去氧富马吉洛尔（4）进行还原胺化合成的，后者是通过氧化富马吉洛尔（2）获得的。还原过程通过氢的赤道攻击进行立体选择性反应，发现5的立体化学与2相同。合成了几种5的衍生物，其中大多数显示出与富马吉洛尔衍生物相当的抗血管生成活性。
• New spiroepoxide tetrahydrobenzo-triazoles and -imidazoles and their use as MetAP-II inhibitors
  申请人：Deutsches Krebsforschungszentrum

  公开号：EP2711367A1

  公开（公告）日：2014-03-26

  The present invention relates to new spiroepoxide tetrahydrobenzo-triazole and - imidazole compounds, a method for their production and their use as MetAP-II inhibitors, which are particularly useful as inhibitors of angiogenesis. The compounds are characterized by formula (I) X=CorN R1 = OC(O)R2 where R2 is alkyl, cycloalkyl, aryl, heteroaryl, or cinnamyl or R1 = OC(O)NHR3 where R3 is alkyl, cycloalkyl, aryl, or heteroaryl or R1 = NHC(O)OR4 where R4 is alkyl or R1 = OH, NH2 R5 = alkyl, cycloalkyl, CH2R6 where R6 is aryl or heteroaryl

  本发明涉及新的螺环氧四氢苯并三唑和咪唑化合物，它们的制备方法以及它们作为MetAP-II抑制剂的用途，特别是作为抑制血管生成的抑制剂。这些化合物的特征是公式（I）X=CorNR1=OC（O）R2，其中R2是烷基，环烷基，芳基，杂芳基或肉桂基，或R1=OC（O）NHR3，其中R3是烷基，环烷基，芳基或杂芳基，或R1=NHC（O）OR4，其中R4是烷基，或R1=OH，NH2，R5=烷基，环烷基，CH2，R6是芳基或杂芳基。
• 5-Demethoxyfumagillol, a Potent Angiogenesis Inhibitor Isolated from Aspergillus fumigatus
  作者：Deukjoon Kim、Jaeki Min、Soon Kil Ahn、Hong Woo Lee、Nam Song Choi、Seung Kee Moon

  DOI：10.1248/cpb.52.447

  日期：——

  A novel angiogenesis inhibitor, 5-demethoxyfumagillol (1), was obtained by isolation, purification and saponification of cultured broth of Aspergillus fumigatus. The structure was assigned as (3R,4R,6R)-4-[(2R,3R)-2-methyl-3-(3-methyl-but-2-enyl)-oxiranyl]-1-oxa-spiro[2,5]octan-6-ol (1) by spectroscopic analysis and confirmed by independent synthesis from fumagillol (3). In addition, 6-O-(chloroacetylcarbamoyl)-5-demethoxyfumagillol (7) showed a potential anti-angiogenic activity in CAPE cells in vitro.

  通过分离、纯化和皂化烟曲霉的培养液，获得了一种新型血管生成抑制剂--5-去甲氧基烟曲霉醇（1）。通过光谱分析，其结构被归类为 (3R,4R,6R)-4-[(2R,3R)-2-甲基-3-(3-甲基-丁-2-烯基)-环氧乙烷基]-1-氧杂螺[2,5]辛烷-6-醇 (1)，并通过与烟曲霉醇 (3) 的独立合成得到证实。此外，6-O-（氯乙酰氨基甲酰基）-5-去甲氧基烟酰醇（7）在体外 CAPE 细胞中显示出潜在的抗血管生成活性。
• Oxaspiro[2.5]Octane Derivatives and Analogs
  申请人：Vath James E.

  公开号：US20150045427A1

  公开（公告）日：2015-02-12

  The invention provides oxaspiro[2.5]octane derivatives and analogs, methods for preparation thereof, intermediates thereto, pharmaceutical compositions, and uses thereof in the treatment of various disorders and conditions, such as overweight and obesity.

  本发明提供了氧杂螺[2.5]辛烷衍生物和类似物，其制备方法，中间体，制药组合物以及在治疗各种疾病和病况（例如超重和肥胖）中的应用。
• Oxaspiro[2.5]octane derivatives and analogs
  申请人：Zafgen, Inc.

  公开号：US10259796B2

  公开（公告）日：2019-04-16

  The invention provides oxaspiro[2.5]octane derivatives and analogs, methods for preparation thereof, intermediates thereto, pharmaceutical compositions, and uses thereof in the treatment of various disorders and conditions, such as overweight and obesity.

  本发明提供了噁螺[2.5]辛烷衍生物和类似物、其制备方法、中间体、药物组合物及其在治疗超重和肥胖等各种疾病和病症中的用途。