(+/-)-3-iso-19-epiajmalicine | 24196-06-3

• 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
• 英文名称: (+/-)-3-iso-19-epiajmalicine
• 英文别名: 19-epi-3-isoajmalicine；methyl (1S,15S,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-pentaene-19-carboxylate
• CAS: 24196-06-3
• 化学式: C₂₁H₂₄N₂O₃
• 分子量: 352.433
• InChiKey: GRTOGORTSDXSFK-BVNXPQQUSA-N

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

• 作为产物：
  描述：

  4,9-二氢-3H-吡啶并(3,4-B)吲哚 在 2,6-二叔丁基-4-甲基吡啶 、 aluminium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 均三甲苯 为溶剂， 反应 116.6h， 生成 (+/-)-3-iso-19-epiajmalicine
  参考文献：
  名称：

  Unified strategy for synthesis of indole and 2-oxindole alkaloids

  摘要：

  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.

  DOI：

  10.1021/ja00016a036

文献信息

• Jokela, Reija; Taipale, Tuula; Ala-Kaila, Kari, Heterocycles, 1986, vol. 24, # 8, p. 2265 - 2271
  作者：Jokela, Reija、Taipale, Tuula、Ala-Kaila, Kari、Lounasmaa, Mauri

  DOI：——

  日期：——
• Stereoselective total synthesis of (±)-3-iso-19-epiajmalicine
  作者：Mauri Lounasmaa、Reija Jokela

  DOI：10.1016/s0040-4039(00)84444-5

  日期：1986.1
• US9138433B2
  申请人：——

  公开号：US9138433B2

  公开（公告）日：2015-09-22