16-decarbomethoxy-21-oxotetrahydroalstonine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 16-decarbomethoxy-21-oxotetrahydroalstonine
• 英文别名: (1S,15R,16S,20R)-16-methyl-17-oxa-3,13-diazapentacyclo[11.8.0.02,10.04,9.015,20]henicosa-2(10),4,6,8,18-pentaen-14-one
• 化学式: C₁₉H₂₀N₂O₂
• 分子量: 308.38
• InChiKey: XKLKKLXCSJGJFO-SYWGBEHUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  23
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  45.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  16-decarbomethoxy-21-oxotetrahydroalstonine 在 2,6-二叔丁基-4-甲基吡啶 、 aluminium hydride 、 sodium cyanoborohydride 、 溶剂黄146 、 三乙胺 作用下， 反应 69.0h， 生成 四氢鸭脚木碱
  参考文献：
  名称：

  异育亨宾和珊瑚虫类吲哚生物碱合成的简明策略。(.+-.)-四氢石蜡碱、(.+-.)-cathenamine 和 (.+-.)-geissoschizine 的全合成

  摘要：

  Synthese des composes du titre via la [butene-2'oyl-2 foryl-3' allyl-1 tetrahydro-1,2,3,4] β-carboline

  DOI：

  10.1021/ja00225a068
• 作为产物：
  描述：

  色胺 在 三氯氧磷 作用下， 以 二氯甲烷 、 均三甲苯 为溶剂， 反应 58.5h， 生成 16-decarbomethoxy-21-oxotetrahydroalstonine
  参考文献：
  名称：

  异育亨宾和珊瑚虫类吲哚生物碱合成的简明策略。(.+-.)-四氢石蜡碱、(.+-.)-cathenamine 和 (.+-.)-geissoschizine 的全合成

  摘要：

  Synthese des composes du titre via la [butene-2'oyl-2 foryl-3' allyl-1 tetrahydro-1,2,3,4] β-carboline

  DOI：

  10.1021/ja00225a068

文献信息

• Biogenetically Inspired Approach to the <i>Strychnos </i>Alkaloids. Concise Syntheses of (±)-Akuammicine and (±)-Strychnine
  作者：Masayuki Ito、Cameron W. Clark、Michael Mortimore、Jane Betty Goh、Stephen F. Martin

  DOI：10.1021/ja010935v

  日期：2001.8.1

  A linear synthesis of the indole alkaloid (+/-)-akuammicine (2) was completed by a novel sequence of reactions requiring only 10 steps from commercially available starting materials. The approach features a tandem vinylogous Mannich addition and an intramolecular hetero Diels-Alder reaction to rapidly assemble the pentacyclic heteroyohimboid derivative 8 from the readily available hydrocarboline 6

  吲哚生物碱 (+/-)-akuammicine (2) 的线性合成是通过新的反应序列完成的，仅需 10 个步骤即可从市售起始材料中提取。该方法具有串联的乙烯基曼尼希加成和分子内杂 Diels-Alder 反应，以从容易获得的烃 6 中快速组装五环杂异菱形衍生物 8。 8 的 E 环的氧化得到内酯 9，该内酯 9 被转化为去甲酰基洋地黄皂苷 (11) . 随后将 11 细化为 2 是通过仿生模式转换实现的，该转换涉及顺序氧化和碱基诱导的骨骼重组。然后将这些策略的变体应用于 C(18) 羟基化草胺衍生物 36 的合成。
• A Biomimetic Approach to the <i>Strychnos </i>Alkaloids. A Novel, Concise Synthesis of (±)-Akuammicine and a Route to (±)-Strychnine
  作者：Stephen F. Martin、Cameron W. Clark、Masayuki Ito、Michael Mortimore

  DOI：10.1021/ja962577f

  日期：1996.1.1
• Unified strategy for synthesis of indole and 2-oxindole alkaloids
  作者：Stephen F. Martin、James E. Hunter、Brigitte Benage、Leo S. Geraci、Michael Mortimore

  DOI：10.1021/ja00016a036

  日期：1991.7

  A concise and general entry to representative indole alkaloids of the yohimboid, heteroyohimboid, corynantheoid, and 2-oxindole classes has been developed exploiting a strategy that features intramolecular Diels-Alder reactions for the facile construction of the D/E ring subunits of the target alkaloids. The efficacy of the approach is first illustrated by a two-step total synthesis of the yohimboid alkaloid oxogambirtannine (2) from 22. Thus, the Diels-Alder substrate 25, which was prepared by nucleophilic addition of vinyl ketene acetal 24 to the intermediate N-acyliminium salt formed in situ upon reaction of 22 with 23, was heated in the presence of benzoquinone to give a mixture of diastereoisomeric cycloadducts 26 and 27; these adducts underwent spontaneous oxidation to furnish 2. In another application of the strategy, the [4 + 2] heterocyclization of 34a, which was formed upon nucleophilic addition of 1-[(trimethylsilyl)oxy]butadiene to the N-acyliminium salt generated in situ upon treatment of 22 with crotonyl chloride, afforded a mixture (ca. 9:1) of cycloadducts 35a and 36a. The major adduct 35a was converted to 42a using a general procedure for effecting beta-carbomethoxylation of enol ethers to give vinylogous carbonates. Subsequent reduction of 42a to the heteroyohimboid alkaloids (+/-)-tetrahydroalstonine (3) and (+/-)-cathenamine (4) was achieved by selective delivery of 2 or 1 equiv of hydride, respectively. When 42a was treated with sodium amide, stereoselective beta-elimination ensued to give 49, which was converted by chemoselective hydride reduction into the corynantheoid alkaloid (+/-)-geissoschizine (5). Facile access to alkaloids of the 2-oxindole family was realized by using a new protocol for achieving stereoselective, oxidative rearrangements of beta-carboline N(b) lactams into 3,3-disubstituted 2-oxindoles. Thus, exposure of 42a to tert-butyl hypochlorite followed by acid and silver ion induced rearrangement of the intermediate 3-chloroindolenine gave 50, with only traces of the C(7) epimer being detected. Hydride reduction of 50 gave (+/-)-isopteropodine (6), acid-catalyzed isomerization of which furnished an equilibrium mixture (1:3) of 6 and (+/-)-pteropodine (51). The stereochemical course of the intramolecular hetero-Diels-Alder reaction of 34a to give 35a and 36a as the only isolable cycloadducts was examined by computational analysis. The geometry of the six-atom transition state was established by semiempirical methods by using the standard closed-shell, restricted Hartree-Fock (RHF) version of the AM1 method. With use of this constrained geometry for the six-membered pericyclic array, the overall conformational energies for the four possible transition states 52-55 were minimized by MM2 calculations (MacroModel). The calculated relative energies of these transition states were in the order 52 < 53 < 54 < 55. Since the cyclization of 34a produced only 35a and 36a in an approximately 9:1 ratio via the respective transition states 52 and 53, these calculations correlated qualitatively with the experimental results.
• Applications of Vinylogous Mannich Reactions. Asymmetric Synthesis of the Heteroyohimboid Alkaloids (-)-Ajmalicine, (+)-19-epi-Ajmalicine, and (-)-Tetrahydroalstonine
  作者：Stephen F. Martin、Cameron W. Clark、Jeffrey W. Corbett

  DOI：10.1021/jo00115a044

  日期：1995.5

  The vinylogous Mannich additions of 1-[(trialkylsilyl)oxy]butadienes to the acyl iminium salt derived from 7 proceeded with a modest degree of stereoselectivity to give a mixture (1.8:1) of 8 and 9. The triene 8 underwent an intramolecular hetero Diels-Alder reaction to give the pentacyclic intermediate 10. Decarboxylation of 10 according to the Barton protocol led to 13, which was then elaborated to (-)-tetrahydroalstonine (1) by a straightforward sequence of reactions. This asymmetric synthesis of 1 required only 10 steps from readily available L-tryptophan. On the other hand, the related vinylogous Mannich addition of a vinyl ketene acetals to 16 were highly stereoselective giving the corresponding trans-substituted hydrocarboline as the only detectable product. Subsequent reaction of this adduct with methyl vinyl ketone followed by cyclization of the intermediate 18 gave the key tetracyclic intermediate 19. Removal of the carboxyl group from the C(5) position of 19 following the Barton procedure gave the ketone 20, which was converted into (-)-ajmalicine (2) in three steps by a known procedure. Alternatively, hydride reduction of the tetracyclic amine 19 gave the alcohol 22, which was subjected to a modified Mitsunobu reaction; selective hydrolysis of the intermediate triester led to the lactone 24. Radical decarboxylation via the Barton procedure gave an intermediate lactone that was converted into (+)-19-epi-ajmalicine (3) in two steps. Removal of the carboxyl presented pathways to both (-)-ajmalicine (2) and (+)-19-epi-ajmalicine (3). Thus, the asymmetric syntheses of 2 and 3 were completed by concise sequences of reactions requiring only 11 and 13 steps, respectively, from D-tryptophan.
• MARTIN, STEPHEN F.;BENAGE, BRIGITTE;HUNTER, JAMES E., J. AMER. CHEM. SOC., 110,(1988) N 17, C. 5925-5927
  作者：MARTIN, STEPHEN F.、BENAGE, BRIGITTE、HUNTER, JAMES E.

  DOI：——

  日期：——