5,6-bis(benzyloxy)-3,4-dihydronaphthalen-1(2H)-one | 59515-93-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 5,6-bis(benzyloxy)-3,4-dihydronaphthalen-1(2H)-one
• 英文别名: 5,6-Dibenzyloxy-3,4-dihydro-1(2H)-naphthalinon；5,6-Dibenzyloxy-3,4-dihydro-1(2H)naphthalenon；1(2H)-Naphthalenone, 3,4-dihydro-5,6-bis(phenylmethoxy)-；5,6-bis(phenylmethoxy)-3,4-dihydro-2H-naphthalen-1-one
• CAS: 59515-93-4
• 化学式: C₂₄H₂₂O₃
• 分子量: 358.437
• InChiKey: MVNZQNDXQPGQOE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5,6-bis(benzyloxy)-3,4-dihydronaphthalen-1(2H)-one 在 甲醇 、 lithium aluminium tetrahydride 、 sodium azide 、 溴 、 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 乙醚 、 水 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.5h， 生成 (1R,2R)-2-(benzyl(methyl)amino)-5,6-bis(benzyloxy)-1,2,3,4-tetrahydronaphthalen-1-ol
  参考文献：
  名称：

  [EN] BETA-2 SELECTIVE ADRENERGIC RECEPTOR AGONISTS
  [FR] AGONISTES DE RÉCEPTEUR ADRÉNERGIQUE BÊTA-2 SÉLECTIF

  摘要：

  公开号：

  WO2019112913A9
• 作为产物：
  描述：

  5,6-二甲氧基-1,2,3,4-四氢1-萘酮 在 aluminum (III) chloride 、 sodium iodide 作用下， 以 丙酮 、 甲苯 为溶剂， 反应 18.25h， 生成 5,6-bis(benzyloxy)-3,4-dihydronaphthalen-1(2H)-one
  参考文献：
  名称：

  [EN] BETA-2 SELECTIVE ADRENERGIC RECEPTOR AGONISTS
  [FR] AGONISTES DE RÉCEPTEUR ADRÉNERGIQUE BÊTA-2 SÉLECTIF

  摘要：

  公开号：

  WO2019112913A9

文献信息

• The syntheses and .BETA.-adrenoceptor activities of N-substituted 2-amino-5,6-dihydroxy-1,2,3,4-tetrahydro-1-naphthalenols.
  作者：KATSUMI ITOH、MICHIO MOTOHASHI、HISASHI KURIKI、HIROSADA SUGIHARA、NOBUHIRO INATOMI、MASAO NISHIKAWA、YOSHIKAZU OKA

  DOI：10.1248/cpb.25.2917

  日期：——

  A series of N-substituted 2-amino-5, 6-dihydroxy-1, 2, 3, 4-tetrahydro-1-naphthalenols (1), which are comformationally rigid derivatives of adrenergic catecholamine, were synthesized via three routes ; namely, the synthetic route in which the final step is 1) the reduction of 1-carbonyl group, 2) N-substitution by reductive alkylation of 2-amino group, or 3) removal of protecting groups of the catechol moiety. Several pairs of 1, 2-cis and trans isomers of 1 were prepared by stereoselective reactions or by separation of each stereoisomer with column chromatography or fractional crystallization. Thus, transamino alcohol (9-trans) was afforded by reduction of 2-amino-5, 6-dibenzyloxy-3, 4-dihydro-1 (2H)-naphthalenone (13) with sodium borohydride, while the cis isomer (9-cis) was obtained from 7, 8-dibenzyloxy-1, 2-dihydronaphthalene (19) via an aziridine intermediate. Several of 1 exhibited excellent β2-adrenoceptor activity superior to l-isoproterenol, the trans derivative being more potent than the cis isomer.

  通过三种路线合成了一系列N-取代的2-氨基-5,6-二羟基-1,2,3,4-四氢-1-萘酚(1)，它们是肾上腺素儿茶酚胺的构象刚性衍生物；即，最终步骤为1)1-羰基的还原，2)2-氨基的还原烷基化进行N-取代，或3)除去儿茶酚部分的保护基团的合成路线。通过立体选择性反应或通过柱色谱或分级结晶分离每种立体异构体来制备1的几对1、2-顺式和反式异构体。因此，通过用硼氢化钠还原2-氨基-5,6-二苄氧基-3,4-二氢-1(2H)-萘酮(13)得到反式氨基醇(9-反式)，而顺式异构体(9- cis)是通过氮丙啶中间体从7,8-二苄氧基-1,2-二氢萘(19)获得的。 1 种中的几种表现出优于 l-异丙肾上腺素的优异 β2-肾上腺素受体活性，反式衍生物比顺式异构体更有效。
• Syntheses of 1,2-N-alkylimino-1,2,3,4-tetrahydronaphthalene derivatives and preparation of ring closed analog of salbutamol as a new .BETA.-adrenoceptor agent.
  作者：HIROSADA SUGIHARA、KIYOSHI UKAWA、AKIO MIYAKE、KATSUMI ITOH、YASUSHI SANNO

  DOI：10.1248/cpb.26.394

  日期：——

  A method for preparing 5-substituted 2-tertiary-alkylamino-6-hydroxy-1, 2, 3, 4-tetrahydro-1-naphthalenols was described. The method involves the preparation of 1-alkylamino-2-hydroxy-1, 2, 3, 4-tetrahydronaphthalenes from 2-bromo-1-hydroxy derivatives via 1, 2-epoxides followed by the transposition of 1-alkylamino and 2-hydroxy groups via the ring closure to 1, 2-aziridines. Formation of the epoxides and aziridines and the reaction of epoxides with amines were examined in detail. The ring-opening reaction of epoxides was regioselective and the attacking position of a nucleophile was not affected by the electronic effects of substituents on the benzene ring. Cyclization into aziridine rings was best accomplished by the Wenker method using a sulfur trioxide-triethylamine adduct as the sulfating agent. Using our process, trans-2-tert-butylamino-6-hydroxy-5-hydroxymethyl-1, 2, 3, 4-tetrahydro-1-naphthalenol (70) was synthesized as conformationally fixed analog of salbutamol.

  描述了一种制备5-取代2-叔烷基氨基-6-羟基-1,2,3,4-四氢-1-萘酚的方法。该方法包括由2-溴-1-羟基衍生物通过1, 2-环氧化物制备1-烷基氨基-2-羟基-1,2,3,4-四氢萘，然后将1-烷基氨基和2-羟基转位基团通过闭环形成1, 2-氮丙啶。详细研究了环氧化物和氮丙啶的形成以及环氧化物与胺的反应。环氧化物的开环反应具有区域选择性，亲核试剂的攻击位置不受苯环上取代基的电子效应影响。环化成氮丙啶环最好通过 Wenker 方法使用三氧化硫-三乙胺加合物作为硫酸化剂来完成。使用我们的方法，合成了反式-2-叔丁基氨基-6-羟基-5-羟甲基-1,2,3,4-四氢-1-萘酚 (70)，作为沙丁胺醇的构象固定类似物。
• OKA JOSHIKAZU; MOTOHASHI MICHIO; SUGIHARA HIROSADA; MIYASHITA OSAMU; ITOH+, CHEM. AND PHARM. BULL., 1977, 25, NO 4, 632-639
  作者：OKA JOSHIKAZU、 MOTOHASHI MICHIO、 SUGIHARA HIROSADA、 MIYASHITA OSAMU、 ITOH+

  DOI：——

  日期：——
• SUGIHARA HIROSADA; UKAWA KIYOSHI; MIYAKE AKIO; ITOH KATSUMI; SANNO ZASUSH+, CHEM. AND PHARM. BULL., 1978, 26, NO 2, 394-404
  作者：SUGIHARA HIROSADA、 UKAWA KIYOSHI、 MIYAKE AKIO、 ITOH KATSUMI、 SANNO ZASUSH+

  DOI：——

  日期：——
• BETA-2 SELECTIVE ADRENERGIC RECEPTOR AGONISTS
  申请人：The Board of Trustees of the Leland Stanford Junior University

  公开号：US20200360304A1

  公开（公告）日：2020-11-19

  Aspects of the present disclosure include conformationally restricted analogs of catecholamine type compounds (e.g., isoprenaline, adrenaline, noradrenaline) which activate β2AR with high selectivity over β1AR. The subject beta-2 selective adrenergic receptor agonist compounds may serve as bronchiodilators and find use in the treatment of a variety of bronchoconstrictive diseases and conditions. Also provided are compositions and methods for treating preterm labor. A method of treating acute asthma including administration of a subject compound to a subject in need thereof is provided. The subject method can provide for reduced undesirable side effects associated with non-selective β-adrenergic receptor agonism, such as inotropic and chronotropic effects that leads to elevated blood pressure. The compounds can also be used to prevent or treat heart failure. Kits and compositions for practicing the subject methods are also provided.