5-Hydroxy-4,6-Di-tert-Butyl-2,2-Dimethyl-2,3-Dihydrobenzofuran | 157360-02-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 香豆素
• 英文名称: 5-Hydroxy-4,6-Di-tert-Butyl-2,2-Dimethyl-2,3-Dihydrobenzofuran
• 英文别名: 4,6-di-t-butyl-5-hydroxy-2,2-dimethyl-2,3-dihydrobenzofuran；4,6-ditert-butyl-2,2-dimethyl-3H-1-benzofuran-5-ol
• CAS: 157360-02-6
• 化学式: C₁₈H₂₈O₂
• 分子量: 276.419
• InChiKey: XZZFNPFTUFXNRE-UHFFFAOYSA-N

物化性质

• 熔点：
  109-110 °C
• 沸点：
  329.5±42.0 °C(Predicted)
• 密度：
  0.987±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-Hydroxy-4,6-Di-tert-Butyl-2,2-Dimethyl-2,3-Dihydrobenzofuran 、 甲烷磺酸 、 碳酸氢钠 在 氯仿 、 Brine 、 magnesium sulfate 、 silica gel 、 正己烷 作用下， 以 氯仿 为溶剂， 反应 4.0h， 以to give 0.09 g of 6-t-butyl-5-hydroxy-2,2-dimethyl-2,3-dihydrobenzofuran as a white solid (yield 41%)的产率得到6-tert-butyl-2,2-dimethyl-2,3-dihydro-benzofuran-5-ol
  参考文献：
  名称：

  2,3-dihydrobenzofuran derivatives

  摘要：

  通式（1）中的2,3-二氢苯并呋喃衍生物：其中R1代表氢原子或酰基；R2、R3和R4代表氢原子、低级烷基或低级烯基；R5和R6代表氢原子或可选取代的烷基，或R5和R6结合形成一个环烷基或饱和含氧或烷基取代的氮原子的杂环基，但R2和R3不能同时代表叔丁基，或其光学异构体或药学上可接受的盐可用作治疗或预防各种肾脏疾病和器官保护剂。

  公开号：

  US06403639B1
• 作为产物：
  描述：

  2,6-二叔丁基-4-甲氧基苯酚 在 盐酸 、 lithium aluminium tetrahydride 、 碘代三甲硅烷 、 硫酸 、 sodium hydride 、 N,N-二甲基苯胺 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 92.75h， 生成 5-Hydroxy-4,6-Di-tert-Butyl-2,2-Dimethyl-2,3-Dihydrobenzofuran
  参考文献：
  名称：

  Design and Synthesis of 4,6-Di-tert-butyl-2,3-dihydro-5-benzofuranols as a Novel Series of Antiatherogenic Antioxidants

  摘要：

  Antioxidants have been considered as potential antiatherogenic agents by inhibiting oxidation of low-density lipoprotein (LDL), albeit vitamin E, a natural antioxidant, has failed to show reduction on atherosclerosis in clinical trials. We have rationally designed and synthesized a novel series of antioxidants, 4,6-di-tert-butyl-2,3-dihydro-5-benzofuranols, to overcome the clinical limitation of vitamin E. In vitro, the compounds showed a potent inhibitory effect on lipid peroxidation detected as 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazo[1,2-a]pyrazin3-one (MCLA)-dependent chemiluminescence in linoleic acid autoxidation. They also inhibited the LDL oxidation induced by Cu2+, and the inhibition is more potent than that of vitamin E and probucol. In vivo, 4,6-di-tert-butyl-2,3-dihydro-2,2-dipentyl-5-benzofuranoI (BO-653, 1f), an optimal compound, showed the highest concentration in plasma and LDL fraction in Watanabe heritable hyperlipidemic rabbits, due to its high affinity to LDL. The isolated LDL samples from the If-treated rabbits showed potent resistibility to LDL oxidation. Compound If has been taken into clinical trials.

  DOI：

  10.1021/jm030062a

文献信息

• 4,6-Di-t-butyl-dihydrobenzofuran-5-ol and its derivatives
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：US05574178A1

  公开（公告）日：1996-11-12

  Compounds represented by the general formula as well as intermediates for the synthesis of thereof: ##STR1## where R.sup.1 is a hydrogen atom or an acyl group; R.sup.2 is a lower alkyl group; R.sup.3 is a hydrogen atom or a lower alkyl group; R.sup.4, R.sup.5 and R.sup.6, which may be the same or different, are a hydrogen atom or an optionally substituted alkyl, alkenyl, alkynyl or aryl group; R.sup.2 and R.sup.4, when taken together, may form a 5-membered ring; R.sup.5 and R.sup.6, when taken together, may form a cycloalkyl group or a heterocyclic group in which at least one methylene on the ring of a cycloalkyl group is substituted by an oxygen atom, a sulfur atom or an alkyl-substituted nitrogen atom, provided that R.sup.6 is not present if the ring formed by R.sup.2 and R.sup.4 taken together is a benzofuran ring. The compounds represented by the general formula (I) have a highly selective anti-oxidative activity and are useful as therapeutics of ischemic diseases such as arteriosclerosis and myocardial infarction.

  通式表示的化合物以及其合成的中间体：##STR1##其中R.sup.1是氢原子或酰基；R.sup.2是较低的烷基；R.sup.3是氢原子或较低的烷基；R.sup.4、R.sup.5和R.sup.6，可以相同也可以不同，是氢原子或可选择取代的烷基、烯基、炔基或芳基；当R.sup.2和R.sup.4一起时，可以形成一个5-成员环；当R.sup.5和R.sup.6一起时，可以形成一个环烷基或一个杂环基，其中环烷基的环上至少有一个甲基被氧原子、硫原子或烷基取代的氮原子取代，前提是如果由R.sup.2和R.sup.4一起形成的环是苯并呋喃环，则R.sup.6不存在。通式（I）表示的化合物具有高度选择性的抗氧化活性，并且可用作治疗缺血性疾病，如动脉粥样硬化和心肌梗死的药物。
• Stability and Reactivity of Aryloxyl Radicals Derived from a Novel Antioxidant BO-653 and Related Compounds. Effects of Substituent and Side Chain in Solution and Membranes
  作者：Akira Watanabe、Noriko Noguchi、Akio Fujisawa、Tatsuhiko Kodama、Kunio Tamura、Osamu Cynshi、Etsuo Niki

  DOI：10.1021/ja9942080

  日期：2000.6.1

  antioxidant, the effects of substituents and side chains on the stability and reactivity of the BO-653 derived radical were studied and compared with the aryloxyl radicals derived from related compounds including α-tocopherol. The rate constants for the reactions of the aryloxyl radicals with themselves, lipid, hydroperoxide, and ascorbate were measured with a stopped-flow electron spin resonance (ESR)

  2,3-Dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butylbenzofuran (BO-653) 是一种新型抗氧化剂，旨在用作抑制体内脂质过氧化的药物。为了了解 BO-653 作为抗氧化剂的作用动力学，我们研究了取代基和侧链对 BO-653 衍生自由基的稳定性和反应性的影响，并与衍生自相关化合物（包括 α-生育酚）的芳氧基自由基进行了比较。芳氧基自由基与自身、脂质、氢过氧化物和抗坏血酸盐反应的速率常数用配备快速混合装置的停流电子自旋共振 (ESR) 光谱仪测量。邻位取代基对双分子衰变反应的速率和与抗坏血酸的反应产生深远的影响，而对与亚油酸甲酯和叔丁基过氧化氢反应的影响要小得多。2-位侧链在有机溶液中没有发挥任何作用，但两个戊基侧链，...
• INTIMAL THICKENING INHIBITOR
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：EP0868913A1

  公开（公告）日：1998-10-07

  An intimal thickening inhibitory agent comprising, as an active ingredient, a compound represented by formula (1): wherein X represents an oxygen atom or a group of formula (2): wherein n represents an integer of from 0 to 2, R1 represents a hydrogen atom or an acyl group; R2 represents a hydrogen atom, a lower alkyl group or a lower alkenyl group; R3 represents a lower alkyl group; and R4, R5, and R6, which may be the same or different, each represent a hydrogen atom or a substituted or unsubstituted alkyl group; or R3 and R4 may be taken together to form a 5-membered ring; or R5 and R6 may be taken together to form a cycloalkyl group; provided that R6 is nil when R3 and R4 are taken together to form benzofuran or benzo[b]thiophene.

  一种内膜增厚抑制剂，其活性成分包括由式（1）代表的化合物： 其中 X 代表氧原子或式（2）的基团： 其中 n 代表 0 至 2 的整数、 R1 代表氢原子或酰基； R2 代表氢原子、低级烷基或低级烯基； R3 代表低级烷基； R4、R5 和 R6 可以相同或不同，各自代表氢原子或取代或未取代的烷基；或 R3 和 R4 组合在一起形成五元环；或 R5 和 R6 组合在一起形成环烷基；但当 R3 和 R4 组合在一起形成苯并呋喃或苯并[b]噻吩时，R6 为零。
• REMEDIES FOR RENAL DISEASES AND ORGAN-PRESERVING AGENTS
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：EP0950405A1

  公开（公告）日：1999-10-20

  Herein disclosed are therapeutic agents for renal diseases and organ preservatives containing a compound represented by the general formula (1): wherein X represents an oxygen atom or a group represented by the general formula (2): where n represents an integer from 0 to 2, R1 represents a hydrogen atom or an acyl group, R2 represents a hydrogen atom, a lower alkyl group or a lower alkenyl group, R3 represents a lower alkyl group, R4, R5 and R6, which may be the same or different, each represents a hydrogen atom or an optionally substituted alkyl group, and R6 further represents a formyl, carboxyl, lower alkoxycarbonyl or optionally substituted carbamoyl group, or R3 and R4 may be taken together to form a five-membered ring, or R5 and R6 may be taken together to form a cycloalkyl group, provided that when the five-membered ring formed by R3 and R4 and the benzene ring form benzofuran or benzo[b]thiophene, R6 is absent.

  这里公开的是含有通式（1）所代表的化合物的肾病治疗剂和器官防腐剂： 其中 X 代表氧原子或通式（2）所代表的基团： 其中 n 代表 0 至 2 的整数，R1 代表氢原子或酰基，R2 代表氢原子、低级烷基或低级烯基，R3 代表低级烷基，R4、R5 和 R6 可以相同或不同，各自代表氢原子或任选取代的烷基，R6 进一步代表甲酰基、羧基、低级烷氧基羰基或低级烷氧基羰基、羧基、低级烷氧基羰基或任选取代的氨基甲酰基，或 R3 和 R4 可结合在一起形成五元环，或 R5 和 R6 可结合在一起形成环烷基，但当 R3 和 R4 形成的五元环与苯环形成苯并呋喃或苯并[b]噻吩时，R6 不存在。
• PREVENTIVES/REMEDIES FOR ARTERIOSCLEROSIS
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：EP0982029A1

  公开（公告）日：2000-03-01

  Herein disclosed are prophylactic/therapeutic agents for atherosclerosis containing a compound of general formula (1): wherein R1 represents a hydrogen atom or an acyl group, R2 represents a lower alkyl group, R3 represents a hydrogen atom or a lower alkyl group, and R4, R5 and R6 represent a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group or an aryl group, or R2 and R4 together with the oxygen atom may form a furan or dihydrofuran ring, or R5 and R6 may combine to form a cycloalkyl group or a heterosubstituted cycloalkyl group in which one or more methylene groups of the cycloalkyl group are replaced by oxygen, sulfur or alkyl-substituted nitrogen atoms, a possible optically active isomer or a pharmaceutically acceptable salt thereof, as an active ingredient.

  本发明公开了含有通式（1）化合物的动脉粥样硬化预防/治疗剂： 其中 R1 代表氢原子或酰基，R2 代表低级烷基，R3 代表氢原子或低级烷基，R4、R5 和 R6 代表氢原子、烷基、烯基、炔基或芳基，或 R2 和 R4 与氧原子一起可形成呋喃或二氢呋喃环、或 R5 和 R6 可结合形成环烷基或杂取代的环烷基，其中环烷基的一个或多个亚甲基被氧、硫或烷基取代的氮原子、可能的光学活性异构体或其药学上可接受的盐取代，作为活性成分。