N-[(7R)-1,2,3,10-四甲氧基-9-氧代-6,7-二氢-5H-苯并[d]庚搭烯-7-基]乙酰胺 | 75520-89-7

• 分子结构分类: 有机化合物 - 碳氢化合物衍生物 - 环庚三烯酮
• 中文名称: N-[(7R)-1,2,3,10-四甲氧基-9-氧代-6,7-二氢-5H-苯并[d]庚搭烯-7-基]乙酰胺
• 英文名称: (+)-(as,7R)-colchicine
• 英文别名: (+)-colchicine；colchicine；(R)-7-Acetylamino-1,2,3,10-tetramethoxy-6,7-dihydro-5H-benzo[a]heptalen-9-on；(+)-Colchicin；(R)-colchicine；N-[(7R)-1,2,3,10-tetramethoxy-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]acetamide
• CAS: 75520-89-7
• 化学式: C₂₂H₂₅NO₆
• 分子量: 399.444
• InChiKey: IAKHMKGGTNLKSZ-MRXNPFEDSA-N

物化性质

• 熔点：
  106-132°C
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  6

ADMET

代谢

(R)-秋水仙碱已知的人类代谢物包括秋水仙碱、3-脱甲基秋水仙碱和2-脱甲基秋水仙碱。

(R)-colchicine has known human metabolites that include Colchiceine, 3-demethylcolchicine, and 2-demethyicolchicine.

来源:NORMAN Suspect List Exchange

反应信息

• 作为产物：
  描述：

  (+/-)-N-(trifluoroacetyl)deacetylcolchiceine 在 碳酸氢钠 、 potassium carbonate 作用下， 以 甲醇 、 乙醚 、 氯仿 、 水 、 丙酮 为溶剂， 反应 5.5h， 生成 N-[(7R)-1,2,3,10-四甲氧基-9-氧代-6,7-二氢-5H-苯并[d]庚搭烯-7-基]乙酰胺
  参考文献：
  名称：

  Facile conversion of natural colchicine into (.+-.)-congeners and (+)-enantiomers including 2-demethyl analogs

  摘要：

  DOI：

  10.1021/jo00363a021

文献信息

• Enantioselective total synthesis of (−)-colchicine, (+)-demecolcinone and metacolchicine: determination of the absolute configurations of the latter two alkaloids
  作者：Bo Chen、Xin Liu、Ya-Jian Hu、Dong-Mei Zhang、Lijuan Deng、Jieyu Lu、Long Min、Wen-Cai Ye、Chuang-Chuang Li

  DOI：10.1039/c7sc01341h

  日期：——

  ee). Moreover, we have also achieved the first syntheses of (+)-demecolcinone and metacolchicine, and determined their absolute configurations. The challenging tricyclic 6-7-7 core of colchicinoids was efficiently introduced using an intramolecular oxidopyrylium-mediated [5 + 2] cycloaddition reaction. Notably, the synthesized colchicinoid 23 exhibited potent inhibitory activity toward the cell growth

  在这里，我们描述了（-）-秋水仙碱的简明，对映选择性和可扩展合成（9.2％的总收率，> 99％ee）。此外，我们还实现了（+）-地美可孕酮和间秋水仙碱的首次合成，并确定了它们的绝对构型。使用分子内氧化吡啶介导的[5 + 2]环加成反应有效地引入了具有挑战性的类秋水仙碱三环6-7-7核心。值得注意的是，合成的类秋水仙碱23对人类癌细胞系的细胞生长具有强大的抑制作用（IC 50 =〜3.0 nM），并且比秋水仙碱对微管组装的抑制作用更大，这使其成为寻找新型抗癌药物的有前途的线索。
• Herstellung des racemischen Colchicins und des unnatürlichen (+)-Colchicins
  作者：H. Corrodi、E. Hardegger

  DOI：10.1002/hlca.19570400123

  日期：——

  Natürliches (−)-Colchicin wurde in das bekannte N-Benzylidendesacetyl-colchicein (III) umgewandelt. III konnte alkalisch racemisiert werden. Aus racemischem III gewonnenes DL-Desacetyl-colchicein wurde mit D-Camphersulfonsäure in die Antipoden (II und IV) zerlegt. Letztere führten nach Acetylierung und Einwirkung von Diazomethan u. a. zum natürlichen (−)-Colchicin und zum unnatürlichen (+)-Colchicin

  Natürliches（−）-Colchicin wurde在das bekannte N-Benzylidendesacetyl-colchicein（III）umgewandelt中。III konntealkalschracemisiertwerden。在Antipoden（II和IV）zerlegt中的Aus racemischem III Gewonnenes DL-Desacetyl-colchicein wurde mitD-Camphersulfonsäure。Letztereführtennach Acetylierung和Einwirkung von Diazomethan ua zumnatürlichen（-）-Colchicin和zumunnatürlichen（+）-Colchicin。DL-秋水仙碱（+）-和（-）-消旋秋水仙碱（Colchicine wie aus
• Biological effects of modified colchicines. Improved preparation of 2-demethylcolchicine, 3-demethylcolchicine, and (+)-colchicine and reassignment of the position of the double bond in dehydro-7-deacetamidocolchicines
  作者：Manfred Roesner、Hans-Georg Capraro、Arthur E. Jacobson、Louise Atwell、Arnold Brossi、Maria A. Iorio、Thomas H. Williams、Robert H. Sik、Colin F. Chignell

  DOI：10.1021/jm00135a005

  日期：1981.3

  A variety of colchicine, demecolcine, and isocolchicine derivatives were examined for their potency in the lymphocytic leukemia P388 screen in mice, for their toxicity in mice, and for their binding to microtubule protein. A qualitatively direct correlation was found between in vivo potency and toxicity; potency appeared to be less well correlated with tubulin binding. The most potent compounds were N-acylated analogues of colchicine and demecolcine. Among the monophenols, only 3-demethylcolchicine showed an appreciable effect in vitro and in vivo and was less toxic than colchicine. Improved methods were found for the preparation of 3- and 2-demethylcolchicine, which involved the use of 85% phosphoric acid and concentrated sulfuric acid, respectively. Decoupling experiments with 1H NMR proved that the double bond of dehydro-7-deacetamidocolchiceine and its derived tropolonic methyl ethers 24 and 25 was in the 5,6 position, rather than the 6,7 position formerly tentatively assigned.
• VARIANTS PREDICTIVE OF RISK OF GOUT
  申请人：Sulem Patrick

  公开号：US20140080727A1

  公开（公告）日：2014-03-20

  Markers on chromosome 19q13, in particular, markers in the ALDH16A1 gene, are associated with risk of gout in humans. Diagnostic applications using the markers, such as determining the susceptibility to Gout, are described.
• BIISOQUINOLINE COMPOUNDS AND METHODS OF TREATMENT
  申请人：UNIVERSITY OF FLORIDA RESEARCH FOUNDATION

  公开号：US20170183349A1

  公开（公告）日：2017-06-29

  The instant invention describes biisoquinoline compounds having therapeutic activity, and methods of treating dis-orders such as cancer, tumors and cell proliferation related disorders, or affect cell differentiation, dedifferentiation or transdifferentiation.

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