(3R^*,11bR^*)-3-ethyl-1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-2H-benzoquinolizin-2-one | 51300-04-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: (3R^*,11bR^*)-3-ethyl-1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-2H-benzoquinolizin-2-one
• 英文别名: 11-trans-3-ethyl-9,10-dimethoxy-3,4,6,7-tetrahydro-1H-pyrido[2,1-a]isoquinolin-2(11bH)-one；3-ethyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-benzoquinolizin-2-one；(+/-)-3c-ethyl-9,10-dimethoxy-(11br)-1,3,4,6,7,11b-hexahydro-pyrido[2,1-a]isoquinolin-2-one；(+/-)-3c-Aethyl-9,10-dimethoxy-(11br)-1,3,4,6,7,11b-hexahydro-pyrido[2,1-a]isochinolin-2-on；rac-2-Oxo-9,10-dimethoxy-3cis-ethyl-1,2,3,4,6,7-hexahydro-(11brefH)-benzochinolizin；Einecs 257-119-8；(3S,11bS)-3-ethyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydrobenzo[a]quinolizin-2-one
• CAS: 51300-04-0
• 化学式: C₁₇H₂₃NO₃
• 分子量: 289.375
• InChiKey: BOBCQOOZINHVMK-FZMZJTMJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  4

上下游信息

反应信息

• 作为反应物：
  描述：

  (3R^*,11bR^*)-3-ethyl-1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-2H-benzoquinolizin-2-one 在 盐酸 作用下， 以 水 、 甲苯 为溶剂， 反应 25.5h， 生成
  参考文献：
  名称：

  脱氢艾美汀在疟疾中重新定位的潜在优势优化。

  摘要：

  药物重新定位为从头设计药物提供了一种有效的替代方法，可以解决对新型抗疟疾治疗方法的紧迫需求。抗厌氧化合物依替丁二盐酸盐已被确认为恶性疟原虫多重耐药菌株K1的有效体外抑制剂（50％抑制浓度[IC50]，47 nM±2.1 nM [平均值±标准偏差]）。据报道，二氢盐酸艾美汀的合成类似物脱氢艾美汀比艾美汀具有更小的心脏毒性作用。根据PDB代码3J7A（恶性疟原虫80S核糖体与依替丁复合），在冷冻电子显微镜（cryo-EM）结构上公开的依替丁结合位点上模拟了两种脱氢曲美汀的非对映异构体的结构，发现（- ）-R，S-脱氢乙美汀比（-）-S更模仿乙美汀的结合姿势，S-脱氢异美汀。还发现（-）-R，S-脱氢异美汀（IC50 71.03±6.1 nM）与（-）-S，S-脱氢异美汀（IC50，2.07± 0.26μM），由于C-1'处构型的变化而失去了效力。除了对恶性疟原虫的无性红细胞生成阶段有影响外，该

  DOI：

  10.1128/aac.01444-19
• 作为产物：
  描述：

  1-chloro-2-(methoxymethoxy)pent-2-ene 在 camphor-10-sulfonic acid 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 生成 (3R^*,11bR^*)-3-ethyl-1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-2H-benzoquinolizin-2-one
  参考文献：
  名称：

  Asymmetric synthesis of benzoquinolizidines: a formal synthesis of (-)-emetine

  摘要：

  Chiral formamidines affixed to tetrahydroisoquinoline derivatives affords the appropriate precursor 9 to various benzo[a]quinolizidines 2 and 3 and dibenzo[a,g]quinolizidines 4 in modest to high optical purity. Both 3 and 4 have been utilized in total syntheses of natural emetine 1, thus the route herein constitutes a formal total synthesis of 1. Furthermore, Mannich cyclizations of 1-alkylisoquinolines 18a-c proceeded with or without loss of absolute stereochemistry at the C-1 position. Explanation for this behavior is based upon whether a [3,3] rearrangement or a Mannich reaction takes place. The former results in virtually complete racemization of 18, whereas the latter totally conserves the chirality in 18. Finally, 1-alkynylisoquinolines of high optical purity were transformed, via the Overman protocol, to alkylidine benzo[a]quinolizidines 24 in good yield and to our knowledge, high enantiomeric excess.

  DOI：

  10.1021/jo00024a032

文献信息

• Redox-Annulation of Cyclic Amines and β-Ketoaldehydes
  作者：Weijie Chen、Daniel Seidel

  DOI：10.1021/acs.orglett.6b00151

  日期：2016.3.4

  Benzo[a]quinolizine-2-one derivatives are readily assembled from 1,2,3,4-tetrahydroisoquinoline and β-ketoaldehydes by means of a new intramolecular redox-Mannich process. These reactions are promoted by simple acetic acid and are thought to involve azomethine ylides as reactive intermediates.

  通过新的分子内氧化还原-曼尼希方法，可以容易地将1,2,3,4-四氢异喹啉和β-酮醛组装成苯并[ a ]喹啉嗪-2-酮衍生物。这些反应通过简单的乙酸促进，并被认为涉及偶氮甲亚胺作为反应性中间体。
• Syntheseversuche in der Emetin-Reihe. 4. Mitteilung. Racemisches 2-Dehydro-emetin
  作者：A. Brossi、M. Baumann、L. H. Chopard-dit-Jean、J. Würsch、F. Schneider、O. Schnider

  DOI：10.1002/hlca.19590420319

  日期：——

  Rac. 2-dehydro-emetine (XV) and rac. 2-dehydro-isoemetine (XVI) have been synthesized in five steps and in good yield from 2-oxo-3-ethyl-9,10-dimethoxy-l, 2,3, 4,6,7-hexahydro-11bH-benzo [a]chinolizine (VII). Homologues and analogues of XV and XVI with other substituents have been obtained in the same way.

  Rac。2-脱氢-依替丁（XV）和rac。由2-氧代-3-乙基-9,10-二甲氧基-1,2,3,4,6,7-六氢-11bH-苯并五步合成2-脱氢异异丁胺（XVI），收率高[a]喹诺酮（VII）。XV和XVI与其他替代物的同系物和类似物已经以相同的方式获得。
• New synthesis of benzo [a]quinolizidin-2-ones via protected 2-aryl-4-piperidones
  作者：Maria Rubiralta、Anna Diez、Antonia Balet、Joan Bosch

  DOI：10.1016/s0040-4020(01)86842-3

  日期：1987.1

  A new synthesis of 9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-benzo aquinolizin-2-one ( and its 3-ethyl derivative via the corresponding 2-(3,4-dimethoxyphenyl)-4-piperidone ethylene acetals is reported. Alkylation of 2-arylpipendires with 2-bromoethanol followed by oxidation of the resulting amino alcohols with oxalyl chloride and dimethyl sulfoxide afforded the aldehydes , which were cyclized with

  -9,10-二甲氧基1,3,4,6,7,11b六氢-2H-苯并一种新的合成一个喹嗪-2-酮（和它的3 -乙基衍生物通过相应的2-（3,4-报道了二甲氧基苯基）-4-哌啶酮乙缩醛，用2-溴乙醇将2-芳基哌啶烷基化，然后用草酰氯和二甲基亚砜氧化生成的氨基醇，得到醛，将其用盐酸环化，得到7-羟基苯并[ α]喹。的减少与trinethylsilane并导致随后的苯并酸水解一个quinolizidin -2-酮。
• Synthesis and antihypertensive activity of a series of spiro[1,3,4,6,7,11b-hexahydro-2H-benzo[a]quinolizine-2,5'-oxazolidin-2'-one]s
  作者：Joan M. Caroon、Robin D. Clark、Arthur F. Kluge、Chi Ho Lee、Arthur M. Strosberg

  DOI：10.1021/jm00364a013

  日期：1983.10

  The 2R*,11bS* and 2S*,11bS* diastereoisomers of the spiro[1,3,4,6,7,11b-hexahydro-2H-benzo[a]quinolizine-2, 5'-oxazolidin-2'-one] system were prepared by stereoselective methods. Evaluation of these compounds for antihypertensive activity by oral administration to the spontaneously hypertensive rat showed the 2S*,11bS* series was the more potent. Within that series it was found that small alkyl substituents at positions 3 and 4' enhanced antihypertensive activity and that methoxyl substitution at positions 9 and 10 was optimal. (2S,3S,11bS)-Spiro-[2-ethyl-9,10-dimethoxy-1,3,4,6,7, 11b-hexahydro-2H-benzo[a]quinolizine-2,5'-oxazolidin-2'-one] [(-)-9e] was one of the most efficacious compounds of this series, while its antipode, (+)-9e, was inactive. Selected compounds in this series were shown to be alpha-adrenoceptor antagonists.
• US2877226
  申请人：——

  公开号：——

  公开（公告）日：——