4-Hydroxy-1,6-bis-(m-methoxyphenyl)-hexan-3-on | 71505-81-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-Hydroxy-1,6-bis-(m-methoxyphenyl)-hexan-3-on
• 英文别名: 4-Hydroxy-1,6-bis(3-methoxyphenyl)hexan-3-one
• CAS: 71505-81-2
• 化学式: C₂₀H₂₄O₄
• 分子量: 328.408
• InChiKey: JVVFSNSDYQQXJB-UHFFFAOYSA-N

物化性质

• 沸点：
  503.3±50.0 °C(Predicted)
• 密度：
  1.124±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-Hydroxy-1,6-bis-(m-methoxyphenyl)-hexan-3-on 在 PPA 作用下， 反应 0.33h， 以86%的产率得到2,8-dimethoxy-5,6,11,12-tetrahydrochrysene
  参考文献：
  名称：

  The Structure and Function of Estrogens. IX. Synthesis of the trans Isomer of 5,5,10b-Trimethyl-4b,5,6,10b,11,12-hexahydrochrysene-2,8-diol

  摘要：

  在碘化锌存在下，酮甲基三甲基硅缩醛（10）与 1ξ-acetoxy- 6-甲氧基-2-（对甲氧基苯基）-2-甲基-1,2,3,4-四氢萘（9）发生烷基化反应，得到 84%的甲基 (1′RS,2′RS)-2-[6′-甲氧基-2′-（对甲氧基苯基）-2?-甲基-1′,2′,3′,4′-四氢萘-1′-基] 乙酸酯（11a）。 用甲磺酸对衍生酸（11b）进行环化，可得到 89%的 2,8-二甲氧基-10b-甲基-顺式-4b,10b,11,12-四氢千里光-6(5H)-酮（12a），用克莱门森还原可得到 52%的 2,8-二甲氧基-4b-甲基-顺式-4b,5,6,10b,11,12-六氢千里光（12b）。用二氯二氰基苯醌氧化 (12b) 得到 70% 的共轭烯酮 (4)，在 10% 钯/炭上氢化后，得到 5:1 比例的 2,8-二甲氧基-10b-甲基-反式-4b,10b,11,12-四氢千里光-6(5H)-酮 (14) 和顺式异构体 (12a)。反式酮（14）的完全甲基化可得到 49%的 2,8-二甲氧基-5,5,10b-三甲基-反式-4b,10b,11,12-四氢千里光烯-6(5H)-酮（16），经克莱门森还原后再进行 O-去甲基化，可得到 5,5,10b-三甲基-反式-4b,5,6,10b,11,12-六氢千里光烯-2,8-二醇（2）。

  DOI：

  10.1071/ch9880735
• 作为产物：
  描述：

  3-(3-甲氧基苯基)-1-丙醇 在 Cl 、 三乙胺 、 pyridinium chlorochromate 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 4-Hydroxy-1,6-bis-(m-methoxyphenyl)-hexan-3-on
  参考文献：
  名称：

  7α,11β-Disubstituted estrogens: Probes for the shape of the ligand binding pocket in the estrogen receptor

  摘要：

  To investigate whether the estrogen receptor accommodates 7 alpha and 11 beta substituents on estradiol in two subsites or in a single subsite, we have prepared three sets of ligands bearing single (7 alpha or 11 beta) or double (7 alpha and 11 beta) substituents and measured their binding affinity. The different behavior of each set precludes a definitive choice, but supports a two subsite model with some limitations. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)10099-3

文献信息

• The Structure and Function of Estrogens. IX. Synthesis of the trans Isomer of 5,5,10b-Trimethyl-4b,5,6,10b,11,12-hexahydrochrysene-2,8-diol
  作者：DJ Collins、JD Cullen

  DOI：10.1071/ch9880735

  日期：——

  Alkylation of ketene methyl trimethylsilyl acetal (10) with 1ξ-acetoxy- 6-methoxy-2-(p- methoxyphenyl )-2-methyl-1,2,3,4-tetrahydronaphthalene (9) in the presence of zinc iodide gave 84% of methyl (1′RS,2′RS)-2- [6′-methoxy-2′-(p-methoxyphenyl )-2?-methyl-1′,2′,3′,4′- tetrahydronaphthalen-1′-yl] ethanoate (11a). Cyclization of the derived acid (11b) with methanesulfonic acid gave 89% of 2,8-dimethoxy-10b-methyl-cis-4b,10b,11,12-tetrahydrochrysen-6(5H)-one (12a), Clemmensen reduction of which afforded 52% of 2,8-dimethoxy-4b-methyl-cis- 4b,5,6,10b,11,12-hexahydrochrysene (12b). Oxidation of (12b) with dichlorodicyanobenzoquinone gave 70% of the conjugated enone (4), which upon hydrogenation over 10% palladium/charcoal gave a 5:1 ratio of 2,8-dimethoxy-10b-methyl-trans-4b,10b,11,12-tetrahydrochrysen-6(5H)-one (14) and the cis isomer (12a). Exhaustive methylation of the trans ketone (14) yielded 49% of 2,8-dimethoxy-5,5,10b-trimethyl-trans-4b,10b,11,12-tetrahydrochrysen-6(5H)-one (16), which upon Clemmensen reduction followed by O- demethylation afforded 5,5,10b-trimethyl-trans-4b,5,6,10b,11,12-hexahydrochrysene-2,8-diol(2).

  在碘化锌存在下，酮甲基三甲基硅缩醛（10）与 1ξ-acetoxy- 6-甲氧基-2-（对甲氧基苯基）-2-甲基-1,2,3,4-四氢萘（9）发生烷基化反应，得到 84%的甲基 (1′RS,2′RS)-2-[6′-甲氧基-2′-（对甲氧基苯基）-2?-甲基-1′,2′,3′,4′-四氢萘-1′-基] 乙酸酯（11a）。 用甲磺酸对衍生酸（11b）进行环化，可得到 89%的 2,8-二甲氧基-10b-甲基-顺式-4b,10b,11,12-四氢千里光-6(5H)-酮（12a），用克莱门森还原可得到 52%的 2,8-二甲氧基-4b-甲基-顺式-4b,5,6,10b,11,12-六氢千里光（12b）。用二氯二氰基苯醌氧化 (12b) 得到 70% 的共轭烯酮 (4)，在 10% 钯/炭上氢化后，得到 5:1 比例的 2,8-二甲氧基-10b-甲基-反式-4b,10b,11,12-四氢千里光-6(5H)-酮 (14) 和顺式异构体 (12a)。反式酮（14）的完全甲基化可得到 49%的 2,8-二甲氧基-5,5,10b-三甲基-反式-4b,10b,11,12-四氢千里光烯-6(5H)-酮（16），经克莱门森还原后再进行 O-去甲基化，可得到 5,5,10b-三甲基-反式-4b,5,6,10b,11,12-六氢千里光烯-2,8-二醇（2）。
• COLLINS D. J.; MATTHEWS W. A., AUSTRAL. J. CHEM., 1979, 32, NO 5, 1093-1106
  作者：COLLINS D. J.、 MATTHEWS W. A.

  DOI：——

  日期：——
• COLLINS, DAVID J.;CULLEN, JOHN D., AUSTRAL. J. CHEM., 41,(1988) N 5, C. 735-744
  作者：COLLINS, DAVID J.、CULLEN, JOHN D.

  DOI：——

  日期：——
• 5,6,11,12-Tetrahydrochrysenes: synthesis of rigid stilbene systems designed to be fluorescent ligands for the estrogen receptor
  作者：Kwang Jin Hwang、James P. O'Neil、John A. Katzenellenbogen

  DOI：10.1021/jo00030a039

  日期：1992.2

  We have prepared a series of tetrahydrochrysenes as fluorescent ligands for the estrogen receptor. The stilbene chromophore in this tetracyclic system is held rigid and is adorned with an electron-donating hydroxyl group at C-8 that corresponds to the phenolic hydroxyl of estrogens and an electron acceptor at C-2 to give a donor-acceptor fluorophore. Additional substituents at C-5 and C-11 provide additional bulk that improves receptor binding affinity without distorting the planar conjugated system. The tetrahydrochrysene core was prepared by an acyloin condensation of alpha-alkyl m-methoxyhydrocinnamate esters, followed by a double dehydrative cyclization. The cis and trans isomers of the alkyl substituted systems could be separated and their stereochemistry ascertained by X-ray crystallographic analysis; the trans isomer has the higher receptor binding affinity, and the derivative with ethyl substituents at C-5 and C-11 has the best affinity. The donor-acceptor systems were prepared by functional group manipulations on one of the aromatic methoxy groups: conversion to the trifluoromethanesulfonate was followed by a palladium-mediated carbonylation to give the acetyl derivative and methoxycarbonylation to give the ester. The ester was further elaborated to the amide and nitrile. The nitro compound was prepared by nitration of protio system, itself prepared by hydrogenolysis of the trifluoromethanesulfonate. As will be described later, these tetrahydrochrysenes provide a favorable combination of estrogen receptor binding affinity and long wavelength, high quantum yield fluorescence to make them useful as fluorescent ligands for the estrogen receptor.
• 7α,11β-Disubstituted estrogens: Probes for the shape of the ligand binding pocket in the estrogen receptor
  作者：Rosanna Tedesco、John A. Katzenellenbogen、Elio Napolitano

  DOI：10.1016/s0960-894x(97)10099-3

  日期：1997.11

  To investigate whether the estrogen receptor accommodates 7 alpha and 11 beta substituents on estradiol in two subsites or in a single subsite, we have prepared three sets of ligands bearing single (7 alpha or 11 beta) or double (7 alpha and 11 beta) substituents and measured their binding affinity. The different behavior of each set precludes a definitive choice, but supports a two subsite model with some limitations. (C) 1997 Elsevier Science Ltd.