methyl 3-benzyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole-5-carboxylate | 66859-30-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - Pyrroloazepines
• 英文名称: methyl 3-benzyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole-5-carboxylate
• 英文别名: Azepino[4,5-B]indole-5-carboxylic acid,1,2,3,4,5,6-hexahydro-3-(phenylmethyl)-,methyl ester；methyl 3-benzyl-2,4,5,6-tetrahydro-1H-azepino[4,5-b]indole-5-carboxylate
• CAS: 66859-30-1
• 化学式: C₂₁H₂₂N₂O₂
• 分子量: 334.418
• InChiKey: BLROAGZNDOJDHY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  45.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 3-benzyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole-5-carboxylate 在 palladium on activated charcoal 盐酸 、 sodium tetrahydroborate 、 氢气 、 溶剂黄146 作用下， 以 甲苯 、 乙腈 为溶剂， 25.0~130.0 ℃ 、101.33 kPa 条件下， 反应 51.0h， 生成 15-nor-18-methoxycoronaridine
  参考文献：
  名称：

  Synthesis and Biological Evaluation of 18-Methoxycoronaridine Congeners. Potential Antiaddiction Agents

  摘要：

  Variation of the methoxycarbonyl and C-18 substituents of the antiaddictive compound 18-methoxycoronaridine, and contraction of its isoquinuclidine ring segment, provided 15 congeners for SAR evaluation at opioid and alpha3beta4 nicotinic acetylcholine receptors. The opioid activities were relatively low, and the alpha3beta4 nicotinic acetylcholine receptor activities were found to correlate with in vivo antiaddictive activities.

  DOI：

  10.1021/jm020562o
• 作为产物：
  描述：

  N_b,N_b-dibenzyl-2-(cyanomethyl)tryptamine 在 palladium on activated charcoal 盐酸 、 sodium tetrahydroborate 、 氢气 、 sodium hydride 、 溶剂黄146 作用下， 以 溶剂黄146 、 苯 为溶剂， 反应 8.0h， 生成 methyl 3-benzyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole-5-carboxylate
  参考文献：
  名称：

  Synthesis of vinca alkaloids and related compounds. 63. A new synthetic pathway for preparing alkaloids and related compounds with the aspidosperma skeleton. Total syntheses of (.+-.)-vincadifformine, (.+-.)-tabersonine, and (.+-.)-oxotabersonine

  摘要：

  Compound 3, which has an indole skeleton containing a masked acryl ester function, was synthesized from the hydrochloride of 2-(ethoxycarbonyl)tryptamine (2). The cycloaddition of 3 with methyl 4-formylhexanoate (21) or with 5-(benzoyloxy)-2-ethylpentanal (33) yielded the starting materials for target compounds (+/-)-vincadifformine (4), (+/-)-3-oxotabersonine (42), and (+/-)-tabersonine (43). The synthesis of vincadifformine (4) was achieved in two different ways: via 3-oxovincadifformine (7) and via tetracyclic benzoate esters 37 and 38. The double bond required in tabersonine (43) and 3-oxotabersonine (42) was introduced by treatment of 3-thioxovincadifformine (39) with p-toluenesulfinyl chloride.

  DOI：

  10.1021/jo00058a025

文献信息

• Syntheses and biological evaluation of vinblastine congeners
  作者：Martin E. Kuehne、William G. Bornmann、Istvan Markó、Yong Qin、Karen L. LeBoulluec、Deborah A. Frasier、Feng Xu、Tshilundu Mulamba、Carol L. Ensinger、Linda S. Borman、Anne E. Huot、Christopher Exon、Fred T. Bizzarro、Julia B. Cheung、Susan L. Bane

  DOI：10.1039/b209990j

  日期：——

  Sixty-two congeners of vinblastine (VLB), primarily with modifications of the piperidine ring in the carbomethoxycleavamine moiety of the binary alkaloid, were synthesized and evaluated for cytotoxicity against murine L1210 leukemia and RCC-2 rat colon cancer cells, and for their ability to inhibit polymerization of microtubular protein at <10−6 M, and for induction of spiralization of microtubular protein, and for microtubular disassembly at 10−4 M concentrations. An ID50 range of >107 M concentrations was found for L1210 inhibition by these compounds, with the most active 1000× as potent as vinblastine.

  合成了长春碱（VLB）的62个类似物，主要是通过改变二元生物碱中碳甲氧基克拉维胺部分的哌啶环来修改结构，并评估了它们对小鼠L1210白血病和大鼠RCC-2结肠癌细胞的细胞毒性，以及它们在<10^-6 M浓度下抑制微管蛋白聚合、诱导微管蛋白螺旋化和在10^-4 M浓度下解聚微管的能力。这些化合物对L1210的抑制作用表现出>10^7 M的ID50范围，其中最活跃的化合物比长春碱的效力高出1000倍。
• The acyclic dienamine–indoloacrylate addition route to catharanthine
  作者：Nan Huang、Tao Jiang、Tiansheng Wang、Mustapha Soukri、Rakesh Ganorkar、Bruce Deker、Jean-Michel Léger、Jose Madalengoitia、Martin E. Kuehne

  DOI：10.1016/j.tet.2008.07.044

  日期：2008.10

  Condensation of methyl 3-benzyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole-5-carboxylate (3) with methyl Z-4-formylhex-3-enoate (6) gave cis-fused dimethyl 5-benzyl-4-ethyl-2,4a,5,6,7,12-hexahydro-1H-benzo[2,3]azepino[4,5-b]indole-2,12b-dicarboxylate and its trans-fused diastereomer. Selective reduction of the less hindered ester group with sodium borohydride to an alcohol ester, tosylation, debenzylation

  3-苄基1,2,3,4,5,6-六氢氮杂环庚烷[4,5- b ]吲哚-5-羧酸甲酯（3）与Z -4-甲酰基己基-3-烯酸酯甲基（6）的缩合反应顺式稠合的二甲基5-苄基-4-乙基-2,4a，5,6,7,12-六氢-1 H-苯并[2,3] azepino [4,5 - b ]吲哚-2,12b-二羧酸酯及其反式非对映异构体。用硼氢化钠将较少受阻的酯基选择性还原为醇酯，进行甲苯磺酸化，脱苄基化和环化反应，得到外消旋的catharanthine（1）。
• Synthesis of vinca alkaloids and related compounds. Part 101: A new convergent synthetic pathway to build up the aspidospermane skeleton. Simple synthesis of 3-oxovincadifformine and 3-oxominovincine. Attempts to produce 15β-hydroxyvincadifformine
  作者：János Éles、György Kalaus、István Greiner、Mária Kajtár-Peredy、Pál Szabó、Lajos Szabó、Csaba Szántay

  DOI：10.1016/s0040-4020(02)01179-1

  日期：2002.10

  A molecule with an indole skeleton, containing a latent acrylic ester function—acting as a diene—was produced from Nb-trityl-2-(hydroxy-methyl)-tryptamine and reacted with esters containing an aldehyde or aldehyde-equivalent structural unit, yielding 3-oxo-16,17-dihydro-Δ20-secodin-17-ol type intermediates from which dehydration, followed by [4+2]cycloaddition, furnished 3-oxovincadifformine and 3-oxominovincine

  由N b-三苯甲基-2-（羟基-甲基）-色胺产生具有吲哚骨架的分子，该分子具有潜在的丙烯酸酯功能（起二烯作用），并与含有醛或醛当量结构单元的酯反应，得到3-氧代-16,17-二氢- Δ 20 -secodin -17-醇型中间体从脱水，接着[4 + 2]环加成，陈设3- oxovincadifformine和3- oxominovincine。我们还希望将该方法用于生产15β-羟基长春新碱，但是，观察到具有吲哚骨架的二聚产物的出现，而不是预期的环加成。
• A novel intramolecular Diels–Alder cyclization involving indoloazepines
  作者：Lianyou Zheng、Tiansheng Wang、Zhonglin Wei、Jinbao Xiang、Xu Bai

  DOI：10.1016/j.tetlet.2005.03.122

  日期：2005.5

  Abstract The reaction of indoloazepines 1 and α,β-unsaturated aldehydes in reflux toluene led to tetracyclic compounds 2 . The key to this reaction was an intramolecular Diels–Alder cycloaddition by the indoloacrylate (dienophile)–dienamine (diene) intermediates generated in situ.

  摘要 吲哚并氮杂 1 与 α,β-不饱和醛在回流甲苯中反应生成四环化合物 2 。该反应的关键是通过原位产生的吲哚丙烯酸酯（亲二烯体）-二烯胺（二烯）中间体进行分子内 Diels-Alder 环加成反应。
• Synthesis of vinblastine and vincristine type compounds
  申请人：University of Vermont & State Agricultural College

  公开号：US04841045A1

  公开（公告）日：1989-06-20

  A new process for the stereospecific synthesis of alkaloids of the vinblastine and vincristine type including the synthesis of vinblastine and vincristine as well novel alkaloids which are active as anti-tumor agents.

  一种新的立体特异性合成长春瑰菜碱和长春花碱类生物碱的方法，包括长春瑰菜碱和长春花碱的合成，以及新型生物碱的合成，这些生物碱作为抗肿瘤药物具有活性。