raumacline | 132923-02-5

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 大灵碱生物碱
• 英文名称: raumacline
• 英文别名: (1S,12S,13S,14R,17S,18S)-17-ethyl-3-methyl-15-oxa-3,20-diazapentacyclo[10.7.1.02,10.04,9.013,18]icosa-2(10),4,6,8-tetraen-14-ol
• CAS: 132923-02-5
• 化学式: C₂₀H₂₆N₂O₂
• 分子量: 326.439
• InChiKey: HJYHBSXUKUQLLJ-SPDOYUGHSA-N

物化性质

• 沸点：
  536.9±50.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  46.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  聚合甲醛 、 raumacline 在 溶剂黄146 sodium cyanoborohydride 作用下， 生成 (-)-N_b-methylraumacline
  参考文献：
  名称：

  在植物细胞培养物阿义马林的生物转化萝芙木serpentina藤：新的吲哚生物碱raumacline和Ñ （b）中-methylraumacline。

  摘要：

  从Rauwolfia serpentina Benth的植物细胞培养物中分离出两种新颖的吲哚生物碱，raumacline（2）和N （b） -methylraumacline（3）。后与进给实验萝芙木生物碱阿义马林（1）。新光谱生物碱的结构通过光谱学方法和阿玛琳的化学合成得以阐明（1）。

  DOI：

  10.1016/s0040-4039(00)97149-1
• 作为产物：
  描述：

  ajmaline 在 sodium tetrahydroborate 、 phosphate buffer 、 2-羟基丙烷-1,2,3-三羧酸根 、 维生素 B2 作用下， 以 甲醇 为溶剂， 反应 37.0h， 生成 raumacline
  参考文献：
  名称：

  从阿玛琳“一锅法”合成雷莫茶碱

  摘要：

  对于Rauwolfia serpentina细胞培养物中ajmaline（1）的生物转化产物生物碱raumacline（2），使用NaBH 4 /核黄素/光介导的1到2的NaBH 4 /核黄素转化，开发了一种有效的“一锅法”合成方法。总产率为86％。

  DOI：

  10.1002/hlca.19930760713

文献信息

• General approach for the synthesis of ajmaline-related alkaloids. Enantiospecific total synthesis of (-)-suaveoline, (-)-raumacline, and (-)-Nb-methylraumacline
  作者：Xiaoyong Fu、James M. Cook

  DOI：10.1021/jo00055a019

  日期：1993.1

  (-)-Raumacline (3) and (-)-Nb-methylraumacline (4), isolated from plant cell cultures of Rauwolfia serpentina Benth., have been synthesized from D-(+)-tryptophan in enantiospecific fashion. In addition, (-)-suaveoline (1) has also been prepared via this strategy. The synthesis of these indole alkaloids employed a stereospecific Pictet-Spengler/Dieckmann protocol to prepare the key intermediate, (-)-N(b)-benzyltetracyclic ketone 12. This ketone 12 was converted into the C-15 functionalized system 16 via an anionic oxy-Cope rearrangement; 16 had also been obtained by 1,4-addition of a Grignard reagent to the alpha,beta-unsaturated aldehyde (-)-8 generated from (-)-12. Conversion of 16 into either (-)-N(b)-benzylsuaveoline (23) or (-)-N(b)-benzylraumacline (28), respectively, is described. Catalytic debenzylation of the hydrochloride salts of 23 and 28 in ethanol provided the corresponding alkaloids (-)-1 and (-)-3 in excellent yield. In contrast to the published reports, the optical rotation of (-)-suaveoline (>98% ee) was found to be [alpha]25D = -9.3-degrees (c = 0.30, CHCl3) rather than 0-degrees as previously reported. Treatment of 23 or 28 (individually) with excess Pd/C and hydrogen in methanol yielded (-)-N(b)-methylsuaveoline and (-)-N(b)-methylraumacline in excellent yield, respectively.

  本研究成功地通过不对称方式利用D-(+)-色氨酸合成了从Rauwolfia serpentina Benth.植物细胞培养物中分离出的(-)-Raumacline(3)和(-)-Nb-甲基raumacline(4)。此外，(-)-Suaveoline(1)也通过该方法成功制备。在吲哚类生物碱的合成过程中，采用了一种立体特异的Pictet-Spengler/Dieckmann协议来制备关键中间体(-)-N(b)-苄基四环酮(12)。随后，通过阴离子氧-Cope重排，将酮12转化为C-15功能化系统16；另外，通过将Grignard试剂与从(-)-12生成的α,β-不饱和醛(-)-8进行1,4-加成，也获得了16。将16分别转化为(-)-N(b)-苄基suaveoline(23)或(-)-N(b)-苄基raumacline(28)的过程得到了详细描述。通过在乙醇中使用乙醇的催化脱苄基反应，分别以优异的产率得到了相应的生物碱(-)-1和(-)-3。与已发布的报告不同，(-)-Suaveoline的光学旋转被发现为[α]D25 = -9.3度（c = 0.30，CHCl3），而不是先前报告的0度。将23或28分别与过量的Pd/C和氢气在甲醇中处理，分别以优异的产率得到了(-)-N(b)-甲基suaveoline和(-)-N(b)-甲基raumacline。
• Total synthesis of (−)-raumacline
  作者：Patrick D. Bailey、Paul D. Clingan、Timothy J. Mills、Richard A. Price、Robin G. Pritchard

  DOI：10.1039/b310274b

  日期：——

  The total synthesis of (−)-raumacline from L-tryptophan was achieved, featuring a cis-specific Pictet–Spengler reaction, a stereoselective Dieckmann cyclization, and an epimerization step that allowed complete stereocontrol of five chiral centres.

  成功实现了从L-色氨酸合成(−)-raumacline的全合成，过程包括一种顺式特异性Pictet–Spengler反应、立体选择性的Dieckmann环化以及一个表异构化步骤，允许对五个手性中心进行完全立体控制。
• Enzymatic biosynthesis of raumacline
  作者：Peter Obitz、Susanne Endreß、Joachim Stöckigt

  DOI：10.1016/0031-9422(95)00503-y

  日期：1995.11

  The indole alkaloid, raumacline, is biosynthesized from ajmaline, when the latter was fed to cell suspensions of Rauwolfia serpentina. Formation in catalysed by two enzymes, a cell wall-bound peroxidase following by a NADPH(2)-dependent reductase. The first enzyme cleaves ajmaline oxidatively leading to a C-21 epimeric mixture of 21-hydroxyraumacline, a novel alkaloid, which, in turn, is reduced under formation of raumacline. The peroxidase reaction is not specific for Rauwolfia cells whereas the reductase is present exclusively in Rauwolfia cell suspensions. The reductase has been purified to homogeneity. The enzyme is highly substrate specific, only accepting 21-hydroxyraumacline and perakine, the latter leading to raucaffrinoline by reduction.
• Debenzylation using catalytic hydrogenolysis in trifluoroethanol, and the total synthesis of (−)-raumacline
  作者：Patrick D. Bailey、Mark A. Beard、Hoa P.T. Dang、Theresa R. Phillips、Richard A. Price、James H. Whittaker

  DOI：10.1016/j.tetlet.2008.01.104

  日期：2008.3

  N-Debenzylations using catalytic hydrogenolysis often fail to take place unless alcoholic solvents are used, but this can lead to N-alkylation as a side reaction; using trifluoroethanol as the solvent overcomes this problem, and leads to highly reliable hydrogenolyses for a wide range of substrates, including the final deprotection step in our total synthesis of (-)-raumacline. (c) 2008 Elsevier Ltd. All rights reserved.
• Enantiospecific total synthesis of the ajmaline related alkaloids (-)-suaveoline, (-)-raumacline, and (-)-Nb-methylraumacline
  作者：Xiaoyong Fu、James M. Cook

  DOI：10.1021/ja00043a043

  日期：1992.8