四氢鸭脚木碱 | 6474-90-4

• 物质功能分类: 天然产物 - 生物碱
• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 育亨宾生物碱
• 中文名称: 四氢鸭脚木碱
• 中文别名: 鸭脚木碱
• 英文名称: (+/-)-tetrahydroalstonine
• 英文别名: tetrahydroalstonine；rac-19α-methyl-(20α)-18-oxa-yohimb-16-ene-16-carboxylic acid methyl ester；rac-(19S)-17,19-epoxy-(20αH)-coryn-16-ene-16-carboxylic acid methyl ester；d,l-Tetrahydro-Alstonin；DL-Tetrahydroalstonin；methyl (1S,15S,16S,20S)-16-methyl-17-oxa-3,13-diazapentacyclo[11.8.0.02,10.04,9.015,20]henicosa-2(10),4,6,8,18-pentaene-19-carboxylate
• CAS: 6474-90-4
• 化学式: C₂₁H₂₄N₂O₃
• 分子量: 352.433
• InChiKey: GRTOGORTSDXSFK-DLLGKBFGSA-N

物化性质

• 熔点：
  227°C
• 沸点：
  524.0±50.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)
• 溶解度：
  溶于氯仿、二氯甲烷、乙酸乙酯、DMSO、丙酮等。
• LogP：
  2.880 (est)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  54.6
• 氢给体数：
  1
• 氢受体数：
  4

制备方法与用途

四氢鸭脚木碱是一种有机物，具有持久的降血糖作用。它是由从Rhazya stricta果实中分离出的一种吲哚生物碱Tetrahydroalstonine，且是一种选择性的α2-肾上腺素受体拮抗剂。

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	rac-19β-methyl-(15β)-18-oxa-yohimb-16-ene-16-carboxylic acid methyl ester	483-03-4	C21H24N2O3	352.433
  ——	16-decarbomethoxy-21-oxotetrahydroalstonine	——	C19H20N2O2	308.38
  缝籽木蓁	(+)-geissoschizine	439-66-7	C21H24N2O3	352.433
  ——	(+/-)-cathenamine	63661-74-5	C21H22N2O3	350.417
  ——	cathenamine	74924-23-5	C21H22N2O3	350.417
  异胡豆苷	strictosidine	20824-29-7	C27H34N2O9	530.575
  ——	1-(4-oxo-2-buten-4-yl)-2-crotonyl-1,2,3,4-tetrahydro-β-carboline	116005-83-5	C19H20N2O2	308.38
  ——	2,3-secoakuammigine	51020-37-2	C21H26N2O3	354.449
  鸭脚木碱,鸡骨常山碱	alstonine	642-18-2	C21H20N2O3	348.401

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  萝巴新	racemic ajmalicine	483-04-5	C21H24N2O3	352.433
  ——	(+)-tetrahydroalstonine	132016-16-1	C21H24N2O3	352.433
  阿枯米精	akuammigine	642-17-1	C21H24N2O3	352.433
  ——	19α-methyl-(20α)-18-oxa-yohimb-16-ene-16-carboxylic acid	72880-91-2	C20H22N2O3	338.406
  ——	10-hydroxytetrahydroalstonine	86940-56-9	C21H24N2O4	368.433
  ——	Na-Boc-tetrahydroalstonine	163083-69-0	C26H32N2O5	452.55
  ——	(+/-)-cathenamine	63661-74-5	C21H22N2O3	350.417
  ——	methyl (1S,4aS,5aS,14aS)-4a,5,5a,6,11,12,14,14a-octahydro-1-methyl-11-oxo-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-4-carboxylate	314295-63-1	C21H22N2O4	366.417
  ——	methyl (1S,4aS,5aS,14aS)-11-ethoxy-4a,5,5a,12,14,14a-hexahydro-1-methyl-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-4-carboxylate	314249-42-8	C23H26N2O4	394.47
  ——	(1S,4aS,5aS,14aS)-11-ethoxy-4a,5,5a,12,14,14a-hexahydro-4-methoxymethyl-1-methyl-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline	314249-44-0	C23H28N2O3	380.487

反应信息

• 作为反应物：
  描述：

  四氢鸭脚木碱 在 sodium tetrahydroborate 、 EDTA-Na₂ 、 mercury(II) diacetate 作用下， 以 甲醇 、 水 为溶剂， 反应 8.33h， 生成 萝巴新
  参考文献：
  名称：

  杂育育亨宾天然产物的对映选择性合成：通过合作催化的统一方法。

  摘要：

  阿尔斯汀和蛇纹石是含有三个连续立体中心的五环吲哚并喹喔啉生物碱（称为“无水安定碱”）。每种药物都具有有趣的生物活性，其中的植物性药物治疗精神病和其他神经系统疾病，其中的主要成分是醛固酮。这项工作描述了这些天然产物的对映选择性全合成，其中关键的步骤是氢键结合/烯胺催化的迈克尔加成反应。

  DOI：

  10.1002/anie.201502011
• 作为产物：
  描述：

  Methyl (19beta)-17-hydroxy-19-methyl-18-oxayohimban-16-carboxylate 在 PPA 作用下， 以 乙二醇二甲醚 为溶剂， 反应 1.0h， 生成 四氢鸭脚木碱
  参考文献：
  名称：

  General methods of synthesis of indole alkaloids. 14. Short routes of construction of yohimboid and ajmalicinoid alkaloid systems and their carbon-13 nuclear magnetic resonance spectral analysis

  摘要：

  DOI：

  10.1021/ja00428a044

文献信息

• Novel N-acylated heterocycles
  申请人：Recordati S.A.

  公开号：US20030162777A1

  公开（公告）日：2003-08-28

  Described are compositions comprising a muscarinic receptor antagonist and an N-acylated heterocycle derivative having affinity for serotonergic receptors, and enantiomers, diastereoisomers, N-oxides, polymorphs, solvates and pharmaceutically acceptable salts thereof. The combination of a muscarinic receptor antagonist and an N-acylated heterocycle, or an enantiomer, diastereoisomer, N-oxide, polymorph, solvate or pharmaceutically acceptable salt thereof, is useful in the treatment of patients with neuromuscular dysfunction of the lower urinary tract and diseases related to 5-HT 1A receptors.

  描述了包含一种肌氨酸受体拮抗剂和一种对5-HT 1A 受体具有亲和力的N-酰化杂环衍生物的组合物，以及它们的对映体、二对映体、N-氧化物、多型体、溶剂合物和药用可接受盐。肌氨酸受体拮抗剂和N-酰化杂环，或其对映体、二对映体、N-氧化物、多型体、溶剂合物或药用可接受盐的组合，在治疗患有下尿路神经肌肉功能障碍和与5-HT 1A 受体相关疾病的患者中是有用的。
• Nitrosated and nitrosylated diuretic compounds, compositions and methods of use
  申请人：Garvey S. David

  公开号：US20050059655A1

  公开（公告）日：2005-03-17

  The invention describes novel nitrosated and/or nitrosylated diuretic compounds or pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated and/or nitrosylated diuretic compound, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides novel compositions and kits comprising at least one diuretic compound of the invention, that is optionally nitrosated and/or nitrosylated, and, optionally, at least one nitric oxide donor compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating conditions resulting from excessive water and/or electrolyte retention; (b) treating cardiovascular diseases; (c) treating renovascular diseases; (d) treating diabetes; (e) treating diseases resulting from oxidative stress; (f) treating endothelial dysfunctions; (g) treating diseases caused by endothelial dysfunctions; (h) treating cirrhosis; (j) treating pre-eclampsia; (k) treating osteoporosis; and (l) treating nephropathy.

  该发明描述了新颖的亚硝基化和/或亚硝酰化利尿化合物或其药用盐，以及包含至少一种亚硝基化和/或亚硝酰化利尿化合物的新型组合物，以及可选地至少一种一氧化氮供体和/或至少一种治疗剂。该发明还提供了包含该发明中至少一种利尿化合物的新型组合物和试剂盒，该利尿化合物可选择地亚硝基化和/或亚硝酰化，并且可选地至少一种一氧化氮供体化合物和/或至少一种治疗剂。该发明还提供了用于(a)治疗由于过多水分和/或电解贮留引起的疾病；(b)治疗心血管疾病；(c)治疗肾血管疾病；(d)治疗糖尿病；(e)治疗由氧化应激引起的疾病；(f)治疗内皮功能障碍；(g)治疗由内皮功能障碍引起的疾病；(h)治疗肝硬化；(j)治疗子痫前期；(k)治疗骨质疏松症；和(l)治疗肾病的方法。
• Nitric oxide enhancing diuretic compounds, compositions and methods of use
  申请人：Garvey S. David

  公开号：US20060189603A1

  公开（公告）日：2006-08-24

  The invention describes novel compositions and kits comprising at least one nitric oxide enhancing diuretic compound, or pharmaceutically acceptable salts thereof, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating conditions resulting from excessive water and/or electrolyte retention; (b) treating cardiovascular diseases; (c) treating renovascular diseases; (d) treating diabetes; (e) treating diseases resulting from oxidative stress; (f) treating endothelial dysfunctions; (g) treating diseases caused by endothelial dysfunctions; (h) treating cirrhosis; (j) treating pre-eclampsia; (k) treating osteoporosis; (l) treating nephropathy; (m) treating peripheral vascular diseases; (n) treating portal hypertension; (o) treating central nervous system disorders; (p) treating metabolic syndrome; (q) treating sexual dysfunctions; and (r) hyperlipidemia. The nitric oxide enhancing diuretic compounds comprise at least one nitric oxide enhancing group linked to the diuretic compound through one or more sites such as carbon, oxygen and/or nitrogen via a bond or moiety that cannot be hydrolyzed.

  该发明描述了包含至少一种增强一氧化氮利尿化合物或其药用盐的新型组合物和试剂盒，以及可选地，至少一种增强一氧化氮化合物和/或至少一种治疗剂的试剂盒。该发明还提供了以下方法：(a)治疗由过多水分和/或电解贮留引起的症状；(b)治疗心血管疾病；(c)治疗肾血管疾病；(d)治疗糖尿病；(e)治疗由氧化应激引起的疾病；(f)治疗内皮功能障碍；(g)治疗由内皮功能障碍引起的疾病；(h)治疗肝硬化；(j)治疗子痫前期；(k)治疗骨质疏松症；(l)治疗肾病；(m)治疗外周血管疾病；(n)治疗门静脉高压；(o)治疗中枢神经系统疾病；(p)治疗代谢综合征；(q)治疗性功能障碍；以及(r)高脂血症。增强一氧化氮利尿化合物包括至少一种增强一氧化氮基团，通过碳、氧和/或氮等一个或多个位点与利尿化合物连接，连接通过不能水解的键或基团。
• [EN] NITRIC OXIDE RELEASING AMINO ACID ESTER COMPOUND, COMPOSITION AND METHOD OF USE<br/>[FR] COMPOSÉ D'ESTER D'ACIDE AMINÉ LIBÉRANT UN OXYDE NITRIQUE, COMPOSITION ET  PROCÉDÉ D'UTILISATION
  申请人：ORAL DELIVERY TECHNOLOGY LTD

  公开号：WO2010034118A1

  公开（公告）日：2010-04-01

  There is provided amino acid ester compounds comprising at least one nitric oxide releasing group, pharmaceutically acceptable salts thereof and compositions thereof. These compounds involve an amino acid side-chain or an amino acid derivative thereof and a nitric oxide releasing group as depicted in the following structures: wherein R1 is either an ethyl or an amino acid side-chain group or an amino acid derivative thereof and R2 is an amino acid side-chain group or an amino acid derivative thereof and n is an integer from 1 to 10.

  提供的氨基酸酯化合物包括至少一个释放一氧化氮基团的化合物，其药学上可接受的盐和组合物。这些化合物涉及氨基酸侧链或其衍生物以及释放一氧化氮基团，如下面的结构所示：其中R1是乙基或氨基酸侧链基团或其衍生物，R2是氨基酸侧链基团或其衍生物，n是从1到10的整数。
• Nitrosated and nitrosylated alpha-adrenergic receptor antagonists, compositions and methods of use
  申请人：——

  公开号：US20020143007A1

  公开（公告）日：2002-10-03

  The present invention describes novel nitrosated and/or nitrosylated &agr;-adrenergic receptor antagonists, and novel compositions containing at least one nitrosated and/or nitrosylated &agr;-adrenergic receptor antagonist, and, optionally, one or more compounds that donate, transfer or release nitric oxide, elevate endogenous levels of endothelium-derived relaxing factor, stimulate endogenous synthesis of nitric oxide or are a substrate for nitric oxide synthase, and/or one or more vasoactive agents. The present invention also provides novel compositions containing at least one &agr;-adrenergic receptor antagonist, and one or more compounds that donate, transfer or release nitric oxide, elevate endogenous levels of endothelium-derived relaxing factor, stimulate endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or one or more vasoactive agents. The present invention also provides methods for treating or preventing sexual dysfunctions in males and females, for enhancing sexual responses in males and females, and for treating or preventing benign prostatic hyperplasia, hypertension, congestive heart failure, variant (Printzmetal) angina, glaucoma, neurodegenerative disorders, vasospastic diseases, cognitive disorders, urge incontinence, or overactive bladder, and for reversing the state of anesthesia.

  本发明描述了新型硝化和/或硝基化α-肾上腺素受体拮抗剂，以及包含至少一种硝化和/或硝基化α-肾上腺素受体拮抗剂的新型组合物，以及可选地包含一种或多种捐赠、转移或释放一氧化氮、提高内源性内皮衍生松弛因子水平、刺激内源性一氧化氮合成或是一氧化氮合成酶底物的化合物，和/或一种或多种血管活性药物。本发明还提供了包含至少一种α-肾上腺素受体拮抗剂和一种或多种捐赠、转移或释放一氧化氮、提高内源性内皮衍生松弛因子水平、刺激内源性一氧化氮合成或是一氧化氮合成酶底物，和/或一种或多种血管活性药物的新型组合物。本发明还提供了用于治疗或预防男性和女性的性功能障碍、增强男性和女性的性反应，以及治疗或预防良性前列腺增生、高血压、充血性心力衰竭、变异性（Printzmetal）心绞痛、青光眼、神经退行性疾病、血管痉挛性疾病、认知障碍、急迫性尿失禁或过度活跃膀胱，以及逆转麻醉状态的方法。