(4R,4aR,7S,7aR,12bS)-3-methyl-2,3,4,4a,7,7a-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7,9-diol | 6912-73-8

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 英文名称: (4R,4aR,7S,7aR,12bS)-3-methyl-2,3,4,4a,7,7a-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7,9-diol
• 英文别名: morphine；7,8-Didehydro-4,5alpha-epoxy-17-methyl-3,6-morphinandiol；(4R,4aR,7aR,12bS)-3-methyl-2,4,4a,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7,9-diol
• CAS: 6912-73-8
• 化学式: C₁₇H₁₉NO₃
• 分子量: 285.343
• InChiKey: BQJCRHHNABKAKU-QWPSNIKLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  21
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  52.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  在 sodium tetrahydroborate 、 双[Α,Α-双(三氟甲基)苯甲醇合]二苯硫 、 三溴化硼 、 苯硫酚 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 1.35h， 生成 (4R,4aR,7S,7aR,12bS)-3-methyl-2,3,4,4a,7,7a-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7,9-diol
  参考文献：
  名称：

  （-）-吗啡的全合成

  摘要：

  （-）-吗啡的不对称全合成已由市售的7-甲氧基-2-四氢萘酮以18个步骤完成。我们的合成方法具有以下特点：从易于制备的手性中间体进行简单转化，通过酸介导的环化作用构建E环，以及单线态氧介导的C环操纵。最后阶段的转化涉及通过原位产生的仲胺的1，6-加成来构建吗啡喃骨架。

  DOI：

  10.1002/chem.201701438

文献信息

• PREPARATION AND UTILITY OF OPIOID ANALGESICS
  申请人：GANT Thomas G.

  公开号：US20080045558A1

  公开（公告）日：2008-02-21

  The present disclosure is directed to modulators of opiate- and/or NMDA receptors and pharmaceutically acceptable salts and prodrugs thereof, the chemical synthesis thereof, and the use of such compounds for the treatment and/or management of pain, anxiety, neurodegeneration, drug dependence, coughing, muscular tension, and/or glaucoma and any other condition in which it is beneficial to modulate an opiate- and/or NMDA receptor.

  本公开涉及阿片和/或NMDA受体的调节剂及其药用盐和前药，其化学合成，以及利用这些化合物治疗和/或管理疼痛、焦虑、神经退行性疾病、药物依赖、咳嗽、肌肉紧张、和/或青光眼以及任何其他有益于调节阿片和/或NMDA受体的情况。
• Conversion of codeine to morphine in isolated capsules of Papaver somniferum
  作者：An-Fei Hsu、Ray H. Liu、Edwin G. Piotrowski

  DOI：10.1016/s0031-9422(00)80750-5

  日期：——

  codeine to morphine was studied in isolated capsules of Papaver somniferum . Cofactors such as nicotinamide adenine dinucleotide, adenosine 5′-triphosphate, S -acetyl coenzyme A and pyridoxal phosphate were not required in the conversion of codeine to morphine. Reducing agents such as dithiothreitol, glutathione and β-mercaptoethanol strongly promoted codeine and morphine degradation, while morphine formation

  摘要 研究了罂粟分离胶囊中可待因向吗啡的生物转化。可待因转化为吗啡不需要烟酰胺腺嘌呤二核苷酸、5'-三磷酸腺苷、S-乙酰辅酶 A 和磷酸吡哆醛等辅助因子。二硫苏糖醇、谷胱甘肽和β-巯基乙醇等还原剂强烈促进可待因和吗啡的降解，而吗啡的形成保持在恒定水平。过氧化氢（浓度 > 0.25 mM）通过非酶促氧化导致可待因和吗啡转化为 N-氧化物。P. somniferum 的分离胶囊提供了一种研究可待因生物转化为吗啡的方法。
• Substituted benzoate ester prodrug derivatives of 3-hydroxymorphinans, intermediates thereto, and processes
  申请人：E.I. DU PONT DE NEMOURS AND COMPANY

  公开号：EP0170090A1

  公开（公告）日：1986-02-05

  Substituted benzoate ester prodrug derivatives of 3-hydroxymorphinans are useful as analgesics or narcotic antagonists and provide enhanced bioavailability of 3-hydroxymorphinans from orally adminstered doses. Relationship to Other Applications This application is a continuation-in-part of copending application Serial No. 627,923, filed July 5, 1984.

  3-hydroxymorphinans 的取代苯甲酸酯原药衍生物可用作镇痛剂或麻醉拮抗剂，并通过口服剂量提高 3-hydroxymorphinans 的生物利用率。 与其他申请的关系 本申请是 1984 年 7 月 5 日提交的序列号为 627,923 的共同申请的部分延续。
• Engineered benzylisoquinoline alkaloid epimerases and methods of producing benzylisoquinoline alkaloids
  申请人：Antheia, Inc.

  公开号：US10544420B2

  公开（公告）日：2020-01-28

  The present disclosure provides systems and methods for increasing production of an alkaloid product through the epimerization of a (S)-1-benzylisoquinoline alkaloid to a (R)-1-benyzlisoquinoline alkaloid via an engineered epimerase in an engineered host cell. A (S)-1-benzylisoquinoline alkaloid is contacted with said engineered epimerase. Contacting said (S)-1-benzylisoquinoline alkaloid with said engineered epimerase converts said (S)-1-benzylisoquinoline alkaloid to said (R)-1-benzylisoquinoline alkaloid.

  本公开提供了通过工程宿主细胞中的工程表聚酶将(S)-1-苄基异喹啉生物碱表聚为(R)-1-苄基异喹啉生物碱来提高生物碱产品产量的系统和方法。将(S)-1-苄基异喹啉生物碱与所述工程表聚酶接触。将所述(S)-1-苄基异喹啉生物碱与所述工程表聚酶接触，将所述(S)-1-苄基异喹啉生物碱转化为所述(R)-1-苄基异喹啉生物碱。
• Abuse-proofed dosage form
  申请人：Bartholomaus Johannes

  公开号：US20050186139A1

  公开（公告）日：2005-08-25

  A solid pharmaceutical dosage form that is safeguarded against abuse, comprising at least one active substance that is susceptible to abuse and at least one emetic that is spatially separate from the at least one active substance. The active substance or substances are present in the form of at least one sub-unit (a), and the at least one emetic is present in the form of at least one sub-unit (b), and the emetic from sub-unit (b) is not activated in the body if the dosage form has been correctly administered as prescribed.

  一种可防止滥用的固体药物剂型，包括至少一种易被滥用的活性物质和至少一种与至少一种活性物质在空间上分离的催吐剂。 活性物质以至少一种亚单位（a）的形式存在，至少一种催吐剂以至少一种亚单位（b）的形式存在，如果按照处方正确服用该剂型，亚单位（b）的催吐剂不会在体内被激活。