4a,5,9,10,11,12-hexahydro-3-methoxy-11-methyl-6H-benzofuro[3a,3,2-ef ][2]benzazepin-6-ol

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 石蒜科生物碱
• 英文名称: 4a,5,9,10,11,12-hexahydro-3-methoxy-11-methyl-6H-benzofuro[3a,3,2-ef ][2]benzazepin-6-ol
• 英文别名: rac-6-methoxy-10-methyl-galantham-1-en-3ξ-ol；(1S,12S)-9-methoxy-4-methyl-11-oxa-4-azatetracyclo[8.6.1.01,12.06,17]heptadeca-6(17),7,9,15-tetraen-14-ol
• 化学式: C₁₇H₂₁NO₃
• 分子量: 287.359
• InChiKey: ASUTZQLVASHGKV-HJOYEKEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  41.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4a,5,9,10,11,12-hexahydro-3-methoxy-11-methyl-6H-benzofuro[3a,3,2-ef ][2]benzazepin-6-ol 在 manganese(IV) oxide 、 氢溴酸 、 L-Selectride 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 水 、 丙酮 为溶剂， 反应 29.0h， 生成 氢溴酸加兰他敏
  参考文献：
  名称：

  Commercial Scale Process of Galanthamine Hydrobromide Involving Luche Reduction: Galanthamine Process Involving Regioselective 1,2-Reduction of α,β-Unsaturated Ketone

  摘要：

  Effect of lanthanide chloride in the Luche regioselective 1,2-reduction of 1-bromo-11-formyl-nornarwedine (5) was studied. Thus, 1-bromo-11-formyl-nornarwedine (5) is reduced with sodium borohydride in the presence of lanthanide chloride to yield 1-bromo-11-formyl-galanthamine isomers (6), which is a key intermediate for the commercial production of highly pure galanthamine hydrobromide (1), a modern drug against Alzheimer's disease.

  DOI：

  10.1021/op300337y
• 作为产物：
  描述：

  1-bromo-4a,5,9,10-tetrahydro-3-methoxy-6-hydroxy-6H-benzofuro[3a,3,2-ef ][2]benzazepin-11(12H)carboxaldehyde 在 lithium aluminium tetrahydride 、 氧气 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以165 g的产率得到4a,5,9,10,11,12-hexahydro-3-methoxy-11-methyl-6H-benzofuro[3a,3,2-ef ][2]benzazepin-6-ol
  参考文献：
  名称：

  Commercial Scale Process of Galanthamine Hydrobromide Involving Luche Reduction: Galanthamine Process Involving Regioselective 1,2-Reduction of α,β-Unsaturated Ketone

  摘要：

  Effect of lanthanide chloride in the Luche regioselective 1,2-reduction of 1-bromo-11-formyl-nornarwedine (5) was studied. Thus, 1-bromo-11-formyl-nornarwedine (5) is reduced with sodium borohydride in the presence of lanthanide chloride to yield 1-bromo-11-formyl-galanthamine isomers (6), which is a key intermediate for the commercial production of highly pure galanthamine hydrobromide (1), a modern drug against Alzheimer's disease.

  DOI：

  10.1021/op300337y

文献信息

• The total synthesis of (±)-lycoramine. Part I
  作者：Naohiko Hazama、Hiroshi Irie、Tamio Mizutani、Tetsuro Shingu、Masao Takada、Shojiro Uyeo、Akira Yoshitake

  DOI：10.1039/j39680002947

  日期：——

  A stepwise synthesis of (±)-lycoramine, an alkaloid of the Amaryllidaceae, has been achieved by initial construction of rings A and B followed by formation of ring C, and finally establishment of ring D. The Dieckmann cyclisation of dimethyl γ-cyano-γ-(3-ethoxy-2-methoxyphenyl)pimelate (VIII), obtained from 3-ethoxy-2-hydroxybenzaldehyde (III) in five steps, gave methyl 5-cyano-5-(3-ethoxy-2-metho

  通过逐步构建环A和B，然后形成环C，最后建立环D，可以实现逐步合成（±）-lycoramine（一种金缕梅科生物碱）。由5-乙氧基-2-羟基苯甲醛（III）分五个步骤制得的γ-氰基-γ-（3-乙氧基-2-甲氧基苯基）二甲基二甲酸酯（VIII）的Dieckmann环化反应得到甲基5-氰基-5-（将3-乙氧基-2-甲氧基苯基）-2-氧代环己烷甲酸酯（IX）转化为4-乙酰氧基-7'-乙氧基-1'，2'-二氢-8'-甲氧基螺[环己烷-1,1'-萘] -4′（3′高）（XXII）通过一系列反应进行，包括Wittig和Friedel-Crafts。在该化合物上进行的施密特反应产生两个异构的内酰胺（VⅤ）和（XXⅥ），后者经N-甲基化，脱乙酰基化并氧化，得到7-乙氧基-2,3,4,5-四氢-6-甲氧基-2-甲基-1 H-螺环[2-苯并ze庚因-5,1'-环乙已烷] -1,4'-二酮（XXX）也可以来自天
• CONSTRUCTS AND METHODS FOR BIOSYNTHESIS OF GALANTHAMINE
  申请人：Donald Danforth Plant Science Center

  公开号：US20190300892A1

  公开（公告）日：2019-10-03

  The present disclosure relates generally to the identification of biosynthetic pathway genes. In particular, it relates to the identification of enzymes within the Amaryllidaceae alkaloid biosynthetic pathway as well as to engineering transgenic organisms for the production of galanthamine and/or hemanthamine and/or lycorine.
• Commercial Scale Process of Galanthamine Hydrobromide Involving Luche Reduction: Galanthamine Process Involving Regioselective 1,2-Reduction of α,β-Unsaturated Ketone
  作者：Ganala Naga Trinadhachari、Anand Gopalkrishna Kamat、Koilpillai Joseph Prabahar、Vijay Kumar Handa、Kukunuri Naga Venkata Satya Srinu、Korupolu Raghu Babu、Paul Douglas Sanasi

  DOI：10.1021/op300337y

  日期：2013.3.15

  Effect of lanthanide chloride in the Luche regioselective 1,2-reduction of 1-bromo-11-formyl-nornarwedine (5) was studied. Thus, 1-bromo-11-formyl-nornarwedine (5) is reduced with sodium borohydride in the presence of lanthanide chloride to yield 1-bromo-11-formyl-galanthamine isomers (6), which is a key intermediate for the commercial production of highly pure galanthamine hydrobromide (1), a modern drug against Alzheimer's disease.