(+/-)-(4aR,8aS)-(4aα,8aα)-4,4a,6,7,8,8a,9,10-octahydro-1,4a,8a-trimethylphenanthren-2(3H)-one | 91237-33-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: (+/-)-(4aR,8aS)-(4aα,8aα)-4,4a,6,7,8,8a,9,10-octahydro-1,4a,8a-trimethylphenanthren-2(3H)-one
• 英文别名: (4aR,8aS)-1,4a,8a-trimethyl-4,6,7,8,9,10-hexahydro-3H-phenanthren-2-one
• CAS: 91237-33-1
• 化学式: C₁₇H₂₄O
• 分子量: 244.377
• InChiKey: FAYHTWDDMCBTHR-DLBZAZTESA-N

物化性质

• 沸点：
  362.4±32.0 °C(Predicted)
• 密度：
  1.03±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (+/-)-(4aR,8aS)-(4aα,8aα)-4,4a,6,7,8,8a,9,10-octahydro-1,4a,8a-trimethylphenanthren-2(3H)-one 在 氨 、 lithium 、 碘甲烷 作用下， 以 四氢呋喃 为溶剂， 以44%的产率得到(+/-)-(1α,4aβ,8aβ,10aα)-3,4,4a,6,7,8,8a,9,10,10a-decahydro-1,4a,8a-trimethylphenanthren-2(3H)-one
  参考文献：
  名称：

  Tricyclic-bis-enone derivatives and methods of use thereof

  摘要：

  提供了新型三环双烯酮衍生物（TBEs）以及制备此类TBEs的方法。还提供了用于预防和/或治疗癌症、阿尔茨海默病、帕金森病、多发性硬化症、肌萎缩侧索硬化、类风湿性关节炎、炎症性肠病以及所有其他疾病的方法，这些疾病的发病机制被认为涉及过量产生一氧化氮（NO）或前列腺素或iNOS或COX-2基因或基因产物的过度表达。此外，本发明的TBE化合物的合成方法利用廉价的商业可获得试剂，具有高成本效益且易于扩展。还提供了利用新型中间体的高效合成方法以及这些中间体的合成。此外，本发明还提供了设计新型水溶性TBEs的方法。

  公开号：

  US20030232786A1
• 作为产物：
  描述：

  2-戊炔-1-醇 在 吡啶 、 氢氧化钾 、 N-氯代丁二酰亚胺 、 lithium aluminium tetrahydride 、 三氟化硼乙醚 、 mercury(II) diacetate 、 sodium methylate 、 三溴化磷 、 sodium hydride 、 二甲基亚砜 作用下， 以 甲醇 、 乙醚 、 溶剂黄146 为溶剂， 反应 20.42h， 生成 (+/-)-(4aR,8aS)-(4aα,8aα)-4,4a,6,7,8,8a,9,10-octahydro-1,4a,8a-trimethylphenanthren-2(3H)-one
  参考文献：
  名称：

  A synthetic approach to the quassinoids

  摘要：

  DOI：

  10.1021/jo00192a004

文献信息

• Synthetic bicyclic analogues of quassinoids
  作者：Caroline C. Lang'at、Robert A. Watt、Istvan Toth、J.David Phillipson

  DOI：10.1016/s0040-4020(98)00368-8

  日期：1998.6

  A series of simple bicyclic analogues of quassinoids have been prepared including compounds with ring A typical of bruceolides and dehydrobruceolides. The synthesis of bicyclic compound 5 and tricyclic analogue 6 was accomplished by acid catalysed Robinson Annelation reaction. Hydroxyketone 9a and its 2-substituted analogues were also prepared to study the structure activity relationship.

  已经制备了一系列简单的类quassinoids双环类似物，包括具有典型的苯丁酸内酯和脱氢溴化内酯的环A的化合物。双环化合物5和三环类似物6的合成是通过酸催化的鲁宾逊退火反应完成的。还制备了羟基酮9a及其2-取代的类似物以研究结构活性关系。
• Efficient synthesis of (−)- and (+)-tricyclic compounds with enone functionalities in rings A and C. A novel class of orally active anti-inflammatory and cancer chemopreventive agents
  作者：Tadashi Honda、Frank G. Favaloro, Jr.、Tomasz Janosik、Yukiko Honda、Nanjoo Suh、Michael B. Sporn、Gordon W. Gribble

  DOI：10.1039/b307491a

  日期：——

  desired to synthesize optically active TBE compounds for a comparison of the biological potency of both enantiomers. We now describe the synthesis of both enantiomers of (4a[small beta],8a[small beta],10a[small alpha])-1,2,4a,6,8a,9,10,10a-octahydro-1,1,4a,8a-tetramethyl-2,6-dioxophenanthren e-3-carbonitrile (2) and 3 from commercially available simple compounds. Interestingly, (+)-3 having the same

  根据合成的三萜类化合物2-氰基-3,12-二氧代油酸酯-1,9（11）的结构设计了在环A和环C具有烯酮官能团的新型三环化合物[三环-双-烯酮（TBE）化合物]。 ）-二烯-28-油酸（CDDO）（1），它是预防和/或治疗癌症和炎症性疾病的有前途的候选药物，其发病机理可能涉及一氧化氮（NO）和/或前列腺素的过量生产。一系列外消旋形式的TBE化合物显示出对小鼠巨噬细胞中干扰素-γ（IFN-γ）诱导的NO产生的高抑制活性。这些化合物之一，（+/-）-（4a [小β，8a [小β，10a [小α]）-1,2,4a，6,8a，9,10,10a-八氢-1 ，1,4a，8a-tetramethyl-2,6-dioxophenanthren e-3,7-dicarbonitrile（（+/-）-3），在一项初步研究中，使用硫代乙醇酸酯和IFN-γ诱导的小鼠腹膜炎症，口服活性为15 mg kg（-1）（单次
• Tricyclic Compounds Containing Nonenolizable Cyano Enones. A Novel Class of Highly Potent Anti-Inflammatory and Cytoprotective Agents
  作者：Tadashi Honda、Hidenori Yoshizawa、Chitra Sundararajan、Emilie David、Marc J. Lajoie、Frank G. Favaloro、Tomasz Janosik、Xiaobo Su、Yukiko Honda、Bill D. Roebuck、Gordon W. Gribble

  DOI：10.1021/jm101445p

  日期：2011.3.24

  Forty-four novel tricycles containing nonenolizable cyano enones (TCEs) were designed and synthesized on the basis of a semisynthetic pentacyclic triterpenoid, bardoxolone methyl, which is currently being developed in phase II clinical trials for the treatment of severe chronic kidney disease in diabetic patients. Most of the TCEs having two different kinds of nonenolizable cyano enones in rings A and C are highly potent suppressors of induction of inducible nitric oxide synthase stimulated with interferon-gamma and are highly potent inducers of the cytoprotective enzymes heme oxygenase-1 and NAD(P)H:quinone oxidoreductase-1. Among these compounds, (+/-)-(4bS,8aR,10aS)-10a-ethynyl-4b,8,8-trimethyl-3,7-dioxo-3,4b,7,8,8a,9,10,10a-octahydrophenanthrene-2,6-dicarbonitrile ((+/-)-31) is the most potent in these bioassays in our pool of drug candidates including semisynthetic triterpenoids and synthetic tricycles. These facts strongly suggest that an essential factor for potency is not a triterpenoid skeleton but the cyano enone functionality. Notably, TCE 31 reduces hepatic tumorigenesis induced with aflatoxin in rats. Further preclinical studies and detailed mechanism studies on 31 are in progress.
• Design and Synthesis of Tricyclic Compounds with Enone Functionalities in Rings A and C:  A Novel Class of Highly Active Inhibitors of Nitric Oxide Production in Mouse Macrophages
  作者：Frank G. Favaloro,、Tadashi Honda、Yukiko Honda、Gordon W. Gribble、Nanjoo Suh、Renee Risingsong、Michael B. Sporn

  DOI：10.1021/jm025565f

  日期：2002.10.1

  Novel tricyclic compounds with enone functionalities in rings A and C, which were designed on the basis of the structure of a synthetic triterpenoid, 2-cyano-3,12-dioxo-oleana-1,9(11)-dien-28-oic acid, have been synthesized. Among them, 10 shows high inhibitory activity (IC50 = 1 nM level) against production of nitric oxide induced by interferon-gamma in mouse macrophages and is orally active at 15 mg/kg (once) in a preliminary in vivo study using mouse peritoneal inflammation induced by thioglycollate and interferon-gamma.
• Remote oxidation of perhydrophenanthrenes by template-directed hydrogen atom abstraction.
  作者：Sean Michael Kerwin、Clayton H. Heathcock

  DOI：10.1021/jo00040a050

  日期：1992.7

  The use of Breslow's remote functionalization paradigm for installation of an axial C-7 hydroxy group into a perhydrophenanthrene nucleus, with a view toward synthesis of bruceantin (1), has been investigated. The substrates that were evaluated were 9a-c, 11, 17, 18, and 20. Substrates 9a-c all undergo preferential functionalization at C-12. After oxidative cleavage of the initial photoproduct, ketones 18a-c were obtained in yields of 18-26% (36-41%, based on unrecovered starting material). Unsaturated substrate 11 undergoes remote functionalization exclusively at the secondary allylic position (C-12); enone 20 is obtained in 83% overall yield after oxidative cleavage of the initial photoadduct, 19a,b. Thus, in this system, C-12 appears to be the preferred site of intramolecular functionalization. Attempts to block reaction at this position by the use of saturated ketone 18, the derived ketal 17, or enone 20, were all unsuccessful. In the case of 18 the only photoproduct was the intramolecular pinacol. Enone 20 gave an exceedingly complex mixture, consisting of many products. Ketal 17 afforded the unusual macrocyclic lactone 21 in 33% yield. The main conclusion of this study is that it is difficult to extrapolate from the excellent regioselectivity observed by Breslow in the steroid system to the trans-anti-trans perhydrophenanthrene system, which is only slightly less rigid. A second factor which we believe is important in the system we have studied is the apparently minor perturbation of having an equatorial substituent at C-4. We postulate that this substituent, which was not present in the model steroidal systems investigated previously by Breslow, disfavors functionalization at C-7.