(+/-)-1,2,3,4-tetrahydro-1-(4'-hydroxy-3'-methoxybenzyl)-6-methoxyisoquinolin-7-ol | 55102-37-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: (+/-)-1,2,3,4-tetrahydro-1-(4'-hydroxy-3'-methoxybenzyl)-6-methoxyisoquinolin-7-ol
• 英文别名: 1-(3'-methoxy-4'-hydroxybenzyl)-6-methoxy-7-hydroxy-1,2,3,4-tetrahydroisoquinoline；6-methoxy-1-vanillyl-1,2,3,4-tetrahydro-isoquinolin-7-ol；nororientaline；1-(4-hydroxy-3-methoxy-benzyl)-6-methoxy-1,2,3,4-tetrahydro-isoquinolin-7-ol；6-Methoxy-1-vanillyl-1,2,3,4-tetrahydro-isochinolin-7-ol；1-<3-Methoxy-4-hydroxybenzyl>-6-methoxy-1,2,3,4-tetrahydro-7-isochinolinol；1-[(4-hydroxy-3-methoxyphenyl)methyl]-6-methoxy-1,2,3,4-tetrahydroisoquinolin-7-ol
• CAS: 55102-37-9
• 化学式: C₁₈H₂₁NO₄
• 分子量: 315.369
• InChiKey: WQTCGADWPORGNB-UHFFFAOYSA-N

物化性质

• 熔点：
  183-185 °C
• 沸点：
  517.8±50.0 °C(Predicted)
• 密度：
  1.234±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  71
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (+/-)-1,2,3,4-tetrahydro-1-(4'-hydroxy-3'-methoxybenzyl)-6-methoxyisoquinolin-7-ol 在 钯 作用下， 170.0~175.0 ℃ 、1.6 kPa 条件下， 生成 cristadine
  参考文献：
  名称：

  Die Synthese von 1-Benzylisochinolinen mit Guajacyl-Gruppierung

  摘要：

  DOI：

  10.1007/bf00913844
• 作为产物：
  描述：

  3,4-dihydro-1-(4'-hydroxy-3'-methoxybenzyl)-6-methoxyisoquinolin-7-ol 在 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 17.0h， 以32 g的产率得到(+/-)-1,2,3,4-tetrahydro-1-(4'-hydroxy-3'-methoxybenzyl)-6-methoxyisoquinolin-7-ol
  参考文献：
  名称：

  [EN] TETRAHYDROPROTOBERBINE COMPOUNDS AND USES THEREOF IN THE TREATMENT OF NEUROLOGICAL, PSYCHIATRIC AND NEURODEGENERATIVE DISEASES
  [FR] COMPOSÉS TÉTRAHYDROPROTOBERBINES ET LEURS UTILISATIONS DANS LE TRAITEMENT DE MALADIES NEUROLOGIQUES, PSYCHIATRIQUES ET NEURODÉGÉNÉRATIVES

  摘要：

  提供了Tetrahydroprotoberbine (THPB)化合物及其在治疗神经系统、精神疾病和神经退行性疾病中的用途。这些化合物包括d-govadine、l-govadine和racemic govadine，以及通式(I)的d-THPBs。还提供了制备通式(I)化合物和d-、l-govadine的对映选择性过程。(I)

  公开号：

  WO2013020229A1

文献信息

• Mammalian alkaloids: Synthesis andO-methylation of (S)- and (R)-3?-hydroxycoclaurine and theirN-methylated analogues withS-adenosyl-L-[methyl-14C]methionine in presence of mammalian catecholO-methyltransferase
  作者：Xiao-Shu He、Dragana Tadi?、Malgorzata Brzostowska、Arnold Brossi、Maureen Bell、Cyrus Creveling

  DOI：10.1002/hlca.19910740704

  日期：1991.10.30

  3′-hydroxycoclaurines 3a and 3b and of the N-methylated analogs 5a,b with S-adenosyl-L-[methyl-14C]methionine in presence of mammalian COMT was investigated in vitro. The N-unsubstituted (1S)- and (1R )-isomers 3a and 3b, respectively, afforded almost equal amounts of the corresponding N-norreticuline 4 and N-nororientaline 19, besides two unknown by-products (see Fig. and Table 1). The N-methylated (1S)-isoquinoline

  Ó光学活性3'- hydroxycoclaurines的-Methylation图3a和3b中和的Ñ甲基化的类似物5a，5b中与小号-adenosyl -1- [甲基- 14 C]在哺乳动物的存在甲硫氨酸COMT研究了体外。的Ñ -未被取代的（1小号） -和（1 - [R ）-异构体3A和3B，分别得到相应几乎等量Ñ -norreticuline 4和Ñ -nororientaline 19，除了两种未知的副产物（参见图和表1）。所述Ñ甲基化的（1个小号） -异喹啉5a中，在另一方面，在很大程度上得到（小号）-orientaline（（小号） - 19），而几乎等量混合物（[R）-reticuline（图6b）和（- [R ）从（1R）-对映异构体5b获得-原喹啉（（R）-19）。异喹啉3a，b和5a，b通过Bischler-Napieralski环化制备O-苄基保护的异喹啉10（方案1）
• Anti-HIV benzylisoquinoline alkaloids and flavonoids from the leaves of Nelumbo nucifera, and structure–activity correlations with related alkaloids
  作者：Yoshiki Kashiwada、Akihiro Aoshima、Yasumasa Ikeshiro、Yuh-Pan Chen、Hiroshi Furukawa、Masataka Itoigawa、Toshihiro Fujioka、Kunihide Mihashi、L. Mark Cosentino、Susan L. Morris-Natschke、Kuo-Hsiung Lee

  DOI：10.1016/j.bmc.2004.10.020

  日期：2005.1

  (+)-1(R)-Coclaurine (1) and (-)-1(S)-norcoclaurine (3), together with quercetin 3-O-beta-D-glucuronide (4), were isolated from the leaves of Nelumbo nucifera (Nymphaccae), and identified as anti-HIV principles. Compounds 1 and 3 demonstrated potent anti-HIV activity with EC50 values of 0.8 and <0.8 mug/mL, respectively, and therapeutic index (TI) values of >125 and >25, respectively. Compound 4 was less potent (EC50 2 mug/mL). In a structure-activity relationship study, other benzylisoquinoline, aporphine, and bisbenzylisoquinoline alkaloids, including liensinine (14), negferine (15), and isoliensinine (16), which were previously isolated from the leaves and embryo of Nelumbo nucifera, were evaluated for anti-HIV activity. Compounds 14-16 showed potent anti-HIV activities with EC50 values of <0.8 mug/mL and TI values of >9.9, >8.6, and >6.5, respectively. Nuciferine (12), an aporphine alkaloid, had an EC50 value of 0.8 mug/mL and TI of 36. In addition, synthetic coclaurine analogs were also evaluated. Compounds 1, 3, 12, and 14-16 can serve as new leads for further development of anti-AIDS agents. (C) 2004 Elsevier Ltd. All rights reserved.

  (+)-1(R)-可可碱(1)和(-)-1(S)-去甲可可碱(3)，以及山奈酚-3-O-β-D-葡萄糖醛酸苷(4)，从睡莲(Nelumbo nucifera)叶中分离并鉴定为抗HIV活性成分。化合物1和3表现出强效的抗HIV活性，其EC50值分别为0.8 μg/mL和<0.8 μg/mL，治疗指数(TI)值分别为>125和>25。化合物4的活性较弱，EC50值为2 μg/mL。在结构-活性关系研究中，还评估了其他苄基异喹啉、阿朴啡烷和双苄基异喹啉生物碱，包括 lienisine(14)、negferine(15)和isoliensinine(16)，这些化合物先前从睡莲叶和胚中分离，进一步证实了它们的抗HIV活性。化合物14-16表现出强效抗HIV活性，其EC50值均<0.8 μg/mL，TI值分别为>9.9、>8.6和>6.5。阿朴啡烷生物碱nuciferine(12)的EC50值为0.8 μg/mL，TI值为36。此外，合成的可可碱类似物也进行了评估。化合物1、3、12和14-16可作为开发新型抗AIDS药物的新先导化合物。©2004 Elsevier Ltd. 所有权利保留。
• Three New O-Methyltransferases Are Sufficient for All O-Methylation Reactions of Ipecac Alkaloid Biosynthesis in Root Culture of Psychotria ipecacuanha
  作者：Taiji Nomura、Toni M. Kutchan

  DOI：10.1074/jbc.m109.086157

  日期：2010.3

  ipecacuanha produces ipecac alkaloids, a series of monoterpenoid-isoquinoline alkaloids such as emetine and cephaeline, whose biosynthesis derives from condensation of dopamine and secologanin. Here, we identified three cDNAs, IpeOMT1-IpeOMT3, encoding ipecac alkaloid O-methyltransferases (OMTs) from P. ipecacuanha. They were coordinately transcribed with the recently identified ipecac alkaloid beta-glucosidase

  药用植物Psychotria ipecacuanha 产生吐根生物碱，这是一系列单萜-异喹啉生物碱，如依米丁和头孢碱，其生物合成来源于多巴胺和secologanin 的缩合。在这里，我们鉴定了三个 cDNA，即 IpeOMT1-IpeOMT3，它们编码来自吐根假单胞菌的吐根生物碱 O-甲基转移酶 (OMT)。它们与最近发现的吐根生物碱 β-葡萄糖苷酶 Ipeglu1 协同转录。它们的氨基酸序列彼此密切相关，而不是与参与苄基异喹啉生物碱生物合成的 OMT 相关，而不是与类黄酮 OMT 相关。重组 IpeOMT 酶的表征与 IpeGlu1 的酶学特性的整合表明，通过 IpeOMT1 的 6-O-甲基化，emetine 生物合成从 N-脱乙酰异胡椒苷分枝出来，IpeOMT2 的贡献较小，然后是 IpeGlu1 的去糖基化。苷元异喹啉骨架的 7-羟基在形成与第二个多巴胺分子缩合的原甲基化之前被 IpeOMT3
• ITO K.; TANAKA H., CHEM. AND PHARM. BULL. <CPBT-AL>, 1977, 25, NO 7, 1732-1739
  作者：ITO K.、 TANAKA H.

  DOI：——

  日期：——
• TETRAHYDROPROTOBERBINE COMPOUNDS AND USES THEREOF IN THE TREATMENT OF NEUROLOGICAL, PSYCHIATRIC AND NEURODEGENERATIVE DISEASES
  申请人：MILLER James Jackson

  公开号：US20150306092A1

  公开（公告）日：2015-10-29

  Tetrahydroprotoberbine (THPB) compounds and their use in the treatment of neurological, psychiatric and neurodegenerative diseases is provided. The compounds include d-govadine, l-govadine and racemic govadine, as well as d-THPBs of general formula (I). Enantioselective processes for preparing compounds of formula (I), and d- and l-govadine are also provided.(I)