2-tert-butylestrone | 21003-02-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 2-tert-butylestrone
• 英文别名: (8R,9S,13S,14S)-2-tert-butyl-3-hydroxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-one
• CAS: 21003-02-1
• 化学式: C₂₂H₃₀O₂
• 分子量: 326.479
• InChiKey: YZHXGRUFOZKVNS-RYUMIWLPSA-N

物化性质

• 熔点：
  >239oC (dec.)
• 溶解度：
  可溶于氯仿（少许）、乙醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.68
• 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：

  2-tert-butylestrone 在 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 5.5h， 生成 2-tert-butyl-17β-carbamoyloxyestra-1,3,5(10)-trien-3-ol
  参考文献：
  名称：

  3,17-二取代的2-烷基-1,3,5（10）-三烯-3-醇衍生物：合成，体外和体内抗癌活性。

  摘要：

  雌二醇3,17-O，O-双-氨基磺酸盐抑制类固醇硫酸酯酶（STS），碳酸酐酶（CA），并在被C-2取代时抑制癌细胞的增殖和血管生成。探索了C-2取代和17-氨基磺酸雌二醇-3,17-O，O-双-氨基磺酸盐的替代方法，并开发了有效而实用的合成方法。对人类癌细胞系的评估显示，2-甲基衍生物27（DU145 GI（50）= 0.38 microM）是最活跃的新型双氨基磺酸盐，而2-乙基-17-氨基甲酸酯衍生物52（GI（50）= 0.22 microM） ）被证明是其系列中最活跃的（参见2-ethylestradiol-3,17-O，O-bis-sulfamate 4 GI（50）= 0.21 microM）。较大的C-2取代基对活性有害。X射线晶体学研究了2-甲氧基17-氨基甲酸酯50，与母体双氨基磺酸酯3相比，作为STS抑制剂的出奇地弱13倍。使用乳腺癌和前列腺癌异种移植物证实了4作为口服抗

  DOI：

  10.1021/jm070405v
• 作为产物：
  描述：

  雌酚酮 、 叔丁醇 在 盐酸 、 iron(III) chloride 作用下， 以 水 、 氯苯 为溶剂， 以40%的产率得到2-tert-butylestrone
  参考文献：
  名称：

  布朗斯台德/路易斯酸催化芳香族烷基化与未活化的叔醇或二叔丁基过氧化物的协同合成季碳中心

  摘要：

  涉及环境友好、易于获得的质子酸和铁的双布朗斯台德/路易斯酸催化促进使用二叔丁基过氧化物对富电子芳烃进行位点选择性叔丁基化。这一转变激发了协同布朗斯台德/路易斯酸催化芳族烷基化的发展，该烷基化通过使用未活化的叔醇作为烷基化剂，从而产生新的季碳中心，从而填补了弗里德尔-克来福特反应文献中的空白。通过 DFT 计算证实，路易斯酸具有增强布朗斯台德酸酸度的作用。非烯丙基、非苄基和非炔丙基叔醇的使用代表了弗里德尔-克拉夫茨反应性中尚未开发的领域。

  DOI：

  10.1039/d1sc06422c

文献信息

• The adamantyl carbonium ion as a dehydrogenating agent, its reactions with estrone
  作者：W.H.W. Lunn、E. Farkas

  DOI：10.1016/s0040-4020(01)96851-6

  日期：1968.1

  An unusual and useful dehydrogenation of estrone of Δ9(11)-estrone has been observed on its reaction with the adamantyl carbonium ion. With modified conditions both t-butyl and adamantyl carbonium ion sources gave 2-substituted estrone derivatives in this reaction.

  在与金刚烷基碳酸根离子反应时，已观察到Δ9 （11） -雌酮的雌酮异常且有用的脱氢。在改变的条件下，叔丁基和金刚烷基碳离子源均在该反应中得到2-取代的雌酮衍生物。
• Digitization and validation of a chemical synthesis literature database in the ChemPU
  作者：Simon Rohrbach、Mindaugas Šiaučiulis、Greig Chisholm、Petrisor-Alin Pirvan、Michael Saleeb、S. Hessam M. Mehr、Ekaterina Trushina、Artem I. Leonov、Graham Keenan、Aamir Khan、Alexander Hammer、Leroy Cronin

  DOI：10.1126/science.abo0058

  日期：2022.7.8

  Despite huge potential, automation of synthetic chemistry has only made incremental progress over the past few decades. We present an automatically executable chemical reaction database of 100 molecules representative of the range of reactions found in contemporary organic synthesis. These reactions include transition metal–catalyzed coupling reactions, heterocycle formations, functional group interconversions, and multicomponent reactions. The chemical reaction codes or χDLs for the reactions have been stored in a database for version control, validation, collaboration, and data mining. Of these syntheses, more than 50 entries from the database have been downloaded and robotically run in seven modular ChemPU’s with yields and purities comparable to those achieved by an expert chemist. We also demonstrate the automatic purification of a range of compounds using a chromatography module seamlessly coupled to the platform and programmed with the same language.

  尽管潜力巨大，但合成化学的自动化在过去几十年中仅取得了循序渐进的进展。我们介绍了一个可自动执行的化学反应数据库，其中包含 100 个分子，代表了当代有机合成中的各种反应。这些反应包括过渡金属催化的偶联反应、杂环形成、官能团相互转化和多组分反应。这些反应的化学反应代码或 χDLs 已存储在数据库中，用于版本控制、验证、协作和数据挖掘。在这些合成中，我们从数据库中下载了 50 多个条目，并在 7 个模块化 ChemPU 中以机器人方式运行，其产率和纯度可与专家化学家的水平相媲美。我们还演示了使用与平台无缝耦合并使用相同语言编程的色谱模块自动纯化一系列化合物。
• A-ring substituted 17β-arylsulfonamides of 17β-aminoestra-1,3,5(10)-trien-3-ol as highly potent reversible inhibitors of steroid sulfatase
  作者：Yaser A. Mostafa、Braden Kralt、Praveen P.N. Rao、Scott D. Taylor

  DOI：10.1016/j.bmc.2015.07.019

  日期：2015.9

  Steroid sulfatase (STS) catalyzes the hydrolysis of the sulfate ester group in biologically inactive sulfated steroids to give biologically active steroids. Inhibitors of STS are considered to be potential therapeutics for treating hormone-dependent cancers such as ER+ breast cancer. A series of 4-substituted 17 beta-arylsulfonamides of 17 beta-aminoestra-1,3,5(10)-trien-3-ol were prepared and examined as STS inhibitors. The presence of a NO2 or Br at the 2-position of the A-ring resulted in a decrease in potency compared to their A-ring-unsubstituted counterparts. However the presence of a nitro group or fluorine atom at the 4-position of the A-ring resulted in an increase in potency and one of these compounds exhibited a K-i(app) value of 1 nM. Modeling studies provided insight into how these compounds interact with active site residues. The anti-proliferative activity of the 3'-Br, 3'-CF3, 4-NO2-3'-Br and 4-NO2-3'-CF3 derivatives were examined using the NCI 60-cell-line panel and found to have mean graph midpoint values of 1.9-3.4 mu M. (C) 2015 Elsevier Ltd. All rights reserved.
• Regioselective deuterium labeling of estrone and catechol estrogen metabolites
  作者：Douglas E. Stack、Justin Ritonya、Scott Jakopovic、Brittney Maloley-Lewis

  DOI：10.1016/j.steroids.2014.08.018

  日期：2014.12

  Increased exposure to estrogens and estrogen metabolites is linked with increased rates of breast, ovarian and other human cancers. Metabolism of estrogen can led to formation of electrophilic o-quinones capable of binding to DNA In order to gain insight into the mechanism of estrogen-induced DNA damage, estrone and catechol estrogens derived from estrone, have been regioselectively labeled with deuterium at the 1-position. Estrone-1-d, estrone-1,2,4-d(3), 4-hydroxyestrone-1-d and 2-hydroxyestrone-1-d have been synthesized with or without deuteriums at the 16-position. The key labeling step involves deuterated trifluoroacetic acid exchange catalyzed by t-butyl alcohol. This economical, straightforward labeling technique makes available a range of estrone compounds containing deuterium at the 1-position. (C) 2014 Elsevier Inc. All rights reserved.
• Synthesis of 4-Formyl Estrone Using a Positional Protecting Group and Its Conversion to Other C-4-Substituted Estrogens
  作者：Yong Liu、Byoungmoo Kim、Scott D. Taylor

  DOI：10.1021/jo7017075

  日期：2007.11.1

  [GRAPHICS]4-Formyl estrone was synthesized in overall good yield in three steps starting from estrone. This was achieved by conducting an electrophilic aromatic substitution reaction using formaldehyde, triethylamine, and MgCl2 on 2-tert-butyl estrone, which was readily prepared in 96% yield from estrone using tertbutyl alcohol and BF3OEt2. The tert-butyl group acted as a positional protecting group to prevent reaction at the 2-position. The tert-butyl group was readily removed in good yield using AlCl3 in dichloromethane/CH3NO2. To our knowledge, this represents the first use of a positional protecting group for the synthesis of a C-4-modified estrogen. 4-Formyl estrone was used as a common precursor to obtain a variety of other C-4 modified estrogens in very high yields such as 4-methylestrone and 4-hydroxymethylestrone as well as the novel estrogen 4-carboxyestrone. The syntheses of 4-formyl, -methyl-, and -hydroxymethyl estrone represent dramatic improvements over previously reported syntheses of these compounds.