19-表阿马碱 | 25532-45-0

• 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: 19-表阿马碱
• 英文名称: 19-Epiajmalicine
• 英文别名: 19-Epiajmalicin；methyl (1S,15R,16R,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: 25532-45-0
• 化学式: C₂₁H₂₄N₂O₃
• 分子量: 352.433
• InChiKey: GRTOGORTSDXSFK-XIEZEKGWSA-N

物化性质

• 熔点：
  216 °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。

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

反应信息

• 作为反应物：
  描述：

  19-表阿马碱 在 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 反应 2.0h， 以42%的产率得到16,17-didehydro-16-(hydroxymethyl)-19-methyloxayohimban
  参考文献：
  名称：

  Development of a pharmacophore for inhibition of human liver cytochrome P-450 2D6: molecular modeling and inhibition studies

  摘要：

  To gain insight into the specificity of cytochrome P-450 2D6 toward inhibitors, a preliminary pharmacophore model was built up using strong competitive inhibitors. Ajmalicine (1), the strongest inhibitor known (K(i) = 3 nM) was selected as template because of its rigid structure. The preliminary pharmacophore model was validated by performing inhibition studies with derivatives of ajmalicine (1) and quinidine (9). Bufuralol (18) was chosen as substrate and the metabolite 1'-hydroxybufuralol (19) was separated by high performance liquid chromatography. All incubations were carried out using human liver microsomes after demonstration that the K(i) values obtained with microsomes were in accordance with those obtained with a reconstituted monooxygenase system containing purified cytochrome P-450 2D6. Large differences of K(i) values ranging between 0.005 and 100 muM were observed. Low-energy conformers of tested compounds were fit within the preliminary pharmacophore model. The analysis of steric and electronic properties of these compounds led to the definition of a final pharmacophore model. Characteristic properties are a positive charge on a nitrogen atom and a flat hydrophobic region, the plane of which is almost perpendicular to the N-H axis and maximally extends up to a distance of 7.5 angstrom from the nitrogen atom. Compounds with high inhibitory potency had additional functional groups with negative molecular electrostatic potential and hydrogen bond acceptor properties on the opposite side at respective distances of 4.8-5.5 angstrom and 6.6-7.5 angstrom from the nitrogen atom. The superposition of strong and weak inhibitors led to the definition of an excluded volume map. Compounds that required additional space were not inhibitors. This is apparently the first pharmacophore model for inhibitors of a cytochrome P-450 enzyme and offers the opportunity to classify compounds according to their potency of inhibition. Adverse drug interactions which occur when both substrates and inhibitors of cytochrome P-450 2D6 are applied may be predicted.

  DOI：

  10.1021/jm00061a004
• 作为产物：
  描述：

  萝巴新 生成 19-表阿马碱
  参考文献：
  名称：

  Palmisano, Giovanni; Danieli, Bruno; Lesma, Giordano, Journal of the Chemical Society. Perkin transactions I, 1985, p. 923 - 926

  摘要：

  DOI：

文献信息

• Total synthesis of racemic ajmalicine and 19-epi-ajmalicine
  作者：J�rg Gutzwiller、Giacomo Pizzolato、Milan R. Uskokovi?

  DOI：10.1002/hlca.19810640544

  日期：1981.7.22

  rac.-Ajmalicine (31) and 19-epi-ajmalicine (30) have been synthesized by a convergent route from the preformed D, E-ring moieties 25 and 27 and tryptophyl bromide. Two syntheses of the trans-1-benzoyl-3-vinyl-4-piperidineacetic acid (13), used in the preparation of 25 and 27, are also described.

  外消旋。-阿马里新（31）和19-外延-ajmalicine（30）已经被会聚路径从预成型d合成，E形环部分25和27和色氨酰溴。还描述了在制备25和27中使用的反式-1-苯甲酰基-3-乙烯基-4-哌啶乙酸的两种合成（13）。
• Stereocontrolled synthesis of 19-epiajmalicine from loganin aglucone
  作者：Enrico G. Baggiolini、Giacomo Pizzolato、Milan R. Uskoković

  DOI：10.1016/s0040-4020(01)85952-4

  日期：1988.1

  The rare naturally occurring heteroyohimbine alkaloid 19-epiajmalicine (1) was prepared from loganin aglucone 6 via a sequence which involves as the central step the conversion of the δ-lactone 7, easily derived from 6, to the 6-epielenolic acid acetal 8. After transformation of the latter to the aldehyde ester 12, reductive condensation with tryptamine to give the lactam 13 and Bischler-Napieralski

  稀有的天然异育亨宾生物碱19-epiajmalicine（1）是由loganin aglycone 6通过一个顺序进行的，该顺序涉及将δ-内酯7（很容易衍生自6）衍生为6-表烯酸乙缩醛8作为核心步骤。后者转化为醛酯12后，与色胺进行还原性缩合反应，生成内酰胺13，Bischler-Napieralski反应导致形成所需的生物碱1。
• Mechanism of the biosynthetic conversion of geissoschizine to 19-epi-ajmalicine in
  作者：J. Stöckigt、G. Höfle、A. Pfitzner

  DOI：10.1016/s0040-4039(00)93646-3

  日期：1980.1

  Geissoschizine (8) is enzymatically converted to 19-epi-ajmalicine (7) first by oxidation to the 4,21-dehydro-intermediate (4) of the heteroyohimbine pathway followed by cyclisation and stereospecific reduction.

  首先通过氧化为异育亨宾途径的4,21-脱氢中间体（4），然后环化和立体定向还原，将Geissoschizine（8）酶法转化为19-表艾玛利辛（7）。
• Biomimetic conversion of vincoside into heteroyohimbine alkaloids
  作者：Richard T. Brown、C. Lyn Chapple

  DOI：10.1039/c39740000740

  日期：——

  The indole alkaloids 19-epiajmalicine (11), 3-iso-19-epiajmalicine(10), and their oxindole derivatives, formosanine (13) and isoformosanine (14) have been synthesised from a vincoside derivative in a biogenetically patterned reaction sequence.

  吲哚生物碱19-表艾玛西林（11），3-iso-19-表艾玛西林（10）以及它们的羟吲哚衍生物，甲酸鸟嘌呤（13）和异甲鸟嘌呤（14）已从一种长春菊苷衍生物以生物遗传学模式化的反应顺序合成。
• A 400 mhz 1H NMR study of the eight basic heteroyohimbine alkaloids
  作者：Mauri Lounasmaa、Siew-Kwong Kan

  DOI：10.1016/s0040-4020(01)83129-x

  日期：1980.1

  A 400 MHz 1H NMR study of the eight basic heteroyohimbine alkaloids has permitted the chemical shifts of all the protons to be established and most of the main coupling constants to be determined. A conformational study of the heteroyohimbine structures is presented.

  对八种基本异育亨宾生物碱进行的400 MHz 1 H NMR研究允许确定所有质子的化学位移，并确定大多数主要偶合常数。提出了异育亨宾结构的构象研究。