5-acetoxy-4,6-di-tert-butyl-2-hydroxybenzaldehyde | 157360-29-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚酯
• 英文名称: 5-acetoxy-4,6-di-tert-butyl-2-hydroxybenzaldehyde
• 英文别名: 5-acetoxy-4,6-di-t-butyl-2-hydroxybenzaldehyde；(2,6-ditert-butyl-3-formyl-4-hydroxyphenyl) acetate
• CAS: 157360-29-7
• 化学式: C₁₇H₂₄O₄
• 分子量: 292.375
• InChiKey: ZXLSPBINTBCOEN-UHFFFAOYSA-N

物化性质

• 熔点：
  79 °C
• 沸点：
  390.6±42.0 °C(Predicted)
• 密度：
  1.080±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-acetoxy-4,6-di-tert-butyl-2-hydroxybenzaldehyde 在 lithium aluminium tetrahydride 、 三氟化硼乙醚 、 magnesium 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 9.5h， 生成 4,6-ditert-butylspiro[3H-1-benzofuran-2,4'-oxane]-5-ol
  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
• 作为产物：
  描述：

  2,6-二叔丁基-4-甲氧基苯酚 在 碘代三甲硅烷 、 (CH₂)6N₄ 、 硫酸 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 反应 104.0h， 生成 5-acetoxy-4,6-di-tert-butyl-2-hydroxybenzaldehyde
  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。
• Process for preparation of a benzofuran derivative
  申请人：——

  公开号：US20030204100A1

  公开（公告）日：2003-10-30

  An industrially useful process for producing benzofuran derivatives of formula (1) 1 by formylating a compound of formula (2) 2 (where A 1 is a protective group), followed by reaction with a compound of formula (4) 3 (where X 1 is a halogen atom), then performing a cyclizing reaction and subsequently performing a reaction for hydroxyl group deprotection.

  一种用于生产苯并呋喃衍生物的工业上有用的过程，首先通过对式(2)的化合物进行甲酰化（其中A1是保护基），然后与式(4)的化合物（其中X1是卤素原子）发生反应，随后进行环化反应，最后进行羟基去保护的反应。
• 4,6 Di-t-butyl-5-hydroxy-2,3-dihydrobenzothiophene
  申请人：Chugai Seiyak Kabushiki Kaisha

  公开号：US05789436A1

  公开（公告）日：1998-08-04

  A compound represented by formula (I): ##STR1## wherein R.sub.1 represents a hydrogen atom, a lower alkyl group or an acyl group; R.sub.2 and R.sub.3, which may be the same or different, each represents a hydrogen atom, an optionally substituted alkyl group, or an optionally substituted alkenyl group; R.sub.4 represents a hydrogen atom, an optionally substituted alkyl group, or an optionally substituted alkenyl group, or R.sub.4 forms a double bond between the carbon atom to which R.sub.3 is bonded and the adjacent carbon atom to form a benzothiophene skeleton, or R.sub.3 and R.sub.4 are taken together to form a 5- to 8-membered spiro ring which may contain a hetero atom, e.g., oxygen, sulfur or nitrogen; and n represents an integer of 0 to 2, or a pharmaceutically acceptable salt thereof. The compound of formula (I) exhibits an inhibitory action on the oxidative modification of LDL and is useful as therapeutics of arteriosclerosis.

  化合物的化学式为(I): ##STR1## 其中R.sub.1代表氢原子，低级烷基或酰基；R.sub.2和R.sub.3，可以相同也可以不同，分别代表氢原子、可选取代的烷基或可选取代的烯基；R.sub.4代表氢原子、可选取代的烷基或可选取代的烯基，或R.sub.4与R.sub.3结合形成双键，形成苯并噻吩骨架，或R.sub.3和R.sub.4结合形成5-8成员的螺环，其中可以含有杂原子，例如氧、硫或氮；n代表0到2的整数，或其药学上可接受的盐。化合物(I)表现出对LDL氧化修饰的抑制作用，可用作动脉硬化的治疗药物。
• 4-alkoxy-2, 6-di-t-butylphenol derivatives
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：US05606089A1

  公开（公告）日：1997-02-25

  Compounds represented by the general formula (I), 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（I）所代表的化合物以及其合成中间体： 其中，R.sup.1是氢原子或酰基基团；R.sup.2是较低的烷基基团；R.sup.3是氢原子或较低的烷基基团；R.sup.4，R.sup.5和R.sup.6，可以相同也可以不同，是氢原子或可选取代的烷基，烯基，炔基或芳基基团；当R.sup.2和R.sup.4结合在一起时，可以形成一个5元环；当R.sup.5和R.sup.6结合在一起时，可以形成一个环烷基或杂环基，在环烷基上至少有一个亚甲基被氧原子，硫原子或烷基取代的氮原子所取代，但是当R.sup.2和R.sup.4结合在一起形成苯并呋喃环时，R.sup.6不存在。通式（I）所代表的化合物具有高度选择性的抗氧化活性，可用作缺血性疾病如动脉硬化和心肌梗塞的治疗剂。
• 4,6-DI-t-BUTYL-2,3-DIHYDROBENZOTHIOPHENES WHICH INHIBIT LDL OXIDATION
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：EP0791589A1

  公开（公告）日：1997-08-27

  A compound represented by formula (I): wherein R1 represents a hydrogen atom, a lower alkyl group or an acyl group; R2 and R3, which may be the same or different, each represents a hydrogen atom, an optionally substituted alkyl group, or an optionally substituted alkenyl group; R4 represents a hydrogen atom, an optionally substituted alkyl group, or an optionally substituted alkenyl group, or R4 forms a double bond between the carbon atom to which R3 is bonded and the adjacent carbon atom to form a benzothiophene skeleton, or R3 and R4 are taken together to form a 5- to 8-membered spiro ring which may contain a hetero atom, e.g., oxygen, sulfur or nitrogen; and n represents an integer of 0 to 2, or a pharmaceutically acceptable salt thereof. The compound of formula (I) exhibits an inhibitory action on the oxidative modification of LDL and is useful as therapeutics of arteriosclerosis.

  由式(I)代表的化合物： 其中 R1 代表氢原子、低级烷基或酰基；R2 和 R3 可以相同或不同，各自代表氢原子、任选取代的烷基或任选取代的烯基；R4 代表氢原子、任选取代的烷基或任选取代的烯基，或 R4 在与 R3 键合的碳原子和相邻碳原子之间形成双键以形成苯并噻吩骨架，或 R3 和 R4 合在一起形成 5 至 8 元螺环，该螺环可包含杂原子，例如g.,氧、硫或氮；以及 n 代表 0 至 2 的整数、 或其药学上可接受的盐。式（I）化合物对低密度脂蛋白的氧化修饰具有抑制作用，可作为动脉硬化的治疗药物。