(-)-(4aR,5R)-(4aα,5α)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one | 52842-07-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (-)-(4aR,5R)-(4aα,5α)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one
• 英文别名: (4aR,5R)-(-)-1,4aβ-dimethyl-5β-hydroxy-4,4a,5,6,7,8-hexahydronaphthalen-2(3H)-one；(-)-(4aR,5R)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one；(-)-(4aR,5R)-5-hydroxy-1,4a-dimethyl-4,4a,5,6,7,8-hexahydronaphthalen-2(3H)-one；(4aR,5R)-5-hydroxy-1,4a-dimethyl-3,4,5,6,7,8-hexahydronaphthalen-2-one
• CAS: 52842-07-6
• 化学式: C₁₂H₁₈O₂
• 分子量: 194.274
• InChiKey: AWLPPJIJSFSOPR-VXGBXAGGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (-)-(4aR,5R)-(4aα,5α)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 在 4-甲基苯磺酸吡啶 作用下， 以 丙酮 为溶剂， 反应 5.0h， 生成 (-)-(4aR,8S,8aS,10aS)-(4aα,8α,8aα,10aβ)-3,4,4a,6,7,8,8a,9,10,10a-decahydro-8-hydroxy-1,1,4a,8a-tetramethylphenanthrene-2(1H)-one
  参考文献：
  名称：

  在环A和C中高效合成具有烯酮功能的（-）-和（+）-三环化合物。一类新型的口服活性抗炎和癌症化学预防剂。

  摘要：

  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

  DOI：

  10.1039/b307491a
• 作为产物：
  描述：

  5,8a-二甲基-3,4,8,8a-四氢-1,6-(2H,7H)-萘二酮 在 吡啶 、 sodium tetrahydroborate 、 lipase from wheat germ 作用下， 以 甲醇 、 phosphate buffer 为溶剂， 反应 6.5h， 生成 (-)-(4aR,5R)-(4aα,5α)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one
  参考文献：
  名称：

  Enzymatic resolution of cis- and trans-1,2,3,4,6,7,8,8a-octahydro-8a-methyl-6-oxo-naphthyl acetate derivatives

  摘要：

  Extensive screenings using commercially available enzymes were performed in relation to the asymmetric hydrolysis reactions of the (+/-)-cis-(1, 3 and 5) and (+/-)-trans-1,2,3,4,6,7,8,8a-octahydro-8a-methyl-6-oxo-naphthyl acetates (7, 9 and 11). The combinations of enzymes from plants and cis-equatorial compounds as well as the combinations of lipases from microorganisms and trans-axial-5-methoxycarbonyl acetate showed high enantiomeric ratio in asymmetric hydrolysis. However, the enantiomeric ratio of the combinations of lipases from microorganisms and trans-axial isomers except trans-axial-5-methoxycarbonyl derivative was less satisfactory. High E values (>200) were observed when beta-amylase from wheat and lipase from Candida cylindracea were used for the (+/-)-cis-acetate 1 and the (+/-)-trans-isomer 7, respectively, to obtain the corresponding chiral products with high enantiomeric ratios (>99:1). (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(02)00551-7

文献信息

• Enantiomerically Pure Octahydronaphthalenone and Octahydroindenone: Elaboration of the Substrate Overcame the Specificity of Yeast-Mediated Reduction
  作者：Ken-ichi Fuhshuku、Mina Tomita、Takeshi Sugai

  DOI：10.1002/adsc.200303004

  日期：2003.6

  change into an octahydroindene skeleton retarded the enzymatic reduction and the enantioselectivity fell to E=5–16. Further structural variation into a bicyclo[3.3.0] skeleton led to an exclusive 1,4-conjugate reduction of the α,β-unsaturated carbonyl group, and the above results suggested the participation of plural oxidoreductive enzymes in the whole cell. In turn, among the 2,2-disubstituted cycloalkanediones

  研究了用酵母菌株Torulaspora delbrueckii IFO10921还原双环二酮的底物特异性。尽管这种酵母有效地还原了（S）对映体，具有高对映选择性（E = 126），在八氢萘骨架上引入取代基，以及八氢茚骨架上的结构变化阻碍了酶的还原，对映选择性降至E = 5-16 。进一步的结构变化形成双环[3.3.0]骨架导致α，β-不饱和羰基的排他性1,4-共轭还原，上述结果表明多种氧化还原酶参与了整个细胞。反过来，在2，2-二取代的环烷二酮中，发现了良好的底物，可以通过酵母介导的还原反应得到相应的羟基酮当量。分离出环状半缩醛产物，例如（1 S，6 S）-3-乙基-3-羟基-6-甲基-2-氧杂双环[4.4.0] decan-7-one和（1 S，6 S）-3-羟基-3,6-二甲基-2-氧杂双环[ 4.3.0] nonan-7-one。此外，通过使用风干的，长期可保存的细胞制剂，还原效果很
• Chemical synthesis of tetracyclic terpenes and evaluation of antagonistic activity on endothelin-A receptors and voltage-gated calcium channels
  作者：Jianyu Lu、Angelo Aguilar、Bende Zou、Weier Bao、Serkan Koldas、Aibin Shi、John Desper、Philine Wangemann、Xinmin Simon Xie、Duy H. Hua

  DOI：10.1016/j.bmc.2015.06.055

  日期：2015.9

  A class of tetracyclic terpenes was synthesized and evaluated for antagonistic activity of endothelin-1 (ET-1) induced vasoconstriction and inhibitory activity of voltage-activated Ca2+ channels. Three repeated Robinson annulation reactions were utilized to construct the tetracyclic molecules. A stereoselective reductive Robinson annulation was discovered for the formation of optically pure tricyclic

  合成一类四环萜烯并评估内皮素-1（ET-1）诱导的血管收缩的拮抗活性和电压激活的Ca 2+通道的抑制活性。利用三个重复的鲁滨逊环化反应来构建四环分子。发现了立体选择性还原罗宾逊环空法用于形成光学纯的三环萜烯。发现向四环烯酮（-）- 18的受阻α面立体选择性加成氰化物，随后转化为醛官能受到双环半亚胺（-）- 4的形成的影响。。六个选定的合成四环萜烯在ET-1诱导的沙鼠螺旋mod动脉中的血管收缩中表现出抑制活性，推定的亲和力常数在93至319 nM之间。此外，对一种化合物（-）- 3进行了进一步评估，发现在相似浓度下，其抑制了电压激活的Ca 2+电流，但不影响背根神经节细胞中的Na +或K +电流。这些观察结果暗示了双重作用机制。总之，四环萜烯代表了一类新型的命中分子，用于发现治疗肺动脉高压和血管相关疾病的新药物。
• Synthesis and absolute configuration of brevione B, an allelochemical isolated from Penicillium sp.
  作者：Hirosato Takikawa、Yusuke Imamura、Mitsuru Sasaki

  DOI：10.1016/j.tet.2005.09.129

  日期：2006.1

  Breviones A–E (1–5), allelochemicals isolated from Penicillium brevicompactum Dierckx, are structurally unique diterpenoid derivatives. The first synthesis of both enantiomers of brevione B (2) was accomplished by employing the double SN2′-type tandem reaction as a key step, and the absolute configuration of the naturally occurring 2 was established.

  Breviones A-E（1 - 5）中，从分离的感物质短密青霉Dierckx，在结构上是独特的二萜类化合物的衍生物。brevione B（2）的两个对映异构体的第一次合成是通过使用双S N 2'型串联反应作为关键步骤完成的，并且确定了天然存在的2个对映体的绝对构型。
• 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.
• [EN] PYRIMIDINE TRICYCLIC ENONE DERIVATIVES FOR INHIBITION OF RORγ AND OTHER USES<br/>[FR] DÉRIVÉS ÉNONE DE PYRIMIDINE TRICYCLIQUE POUR L'INHIBITION DE RORγ ET D'AUTRES UTILISATIONS
  申请人：REATA PHARMACEUTICALS INC

  公开号：WO2018111315A8

  公开（公告）日：2019-07-11