2',5-二氯-2'-脱氧胞苷 | 436-41-9

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 麦角林及其衍生物
• 中文名称: 2',5-二氯-2'-脱氧胞苷
• 英文名称: (+)-Costaclavine
• 英文别名: Costaclavin；(6aR,9R,10aS)-7,9-dimethyl-6,6a,8,9,10,10a-hexahydro-4H-indolo[4,3-fg]quinoline
• CAS: 436-41-9
• 化学式: C₁₆H₂₀N₂
• 分子量: 240.348
• InChiKey: VLMZMRDOMOGGFA-RIEGTJTDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  19
• 氢给体数：
  1
• 氢受体数：
  1

ADMET

毒理性

• 毒性总结

麦角生物碱倾向于作为一个整体发挥作用，在肾上腺素能、多巴胺能和血清素能受体上产生复杂且多变的部分激动或拮抗作用。与这些效果相关的变量受到药剂、剂量、物种、组织、生理和内分泌状态以及实验条件的影响。特别是，麦角生物碱已被证明对5-HT1和5-HT2血清素受体、D1和D2多巴胺受体以及α-肾上腺素受体具有显著的亲和力。这可能导致多种不同的效果，包括血管收缩、惊厥和幻觉。

Ergoline alkaloids tend to act as a group, producing complex and variable effects of partial agonism or antagonism at adrenergic, dopaminergic, and serotonergic receptors. Variables relating to these effects are influenced by the agent, dosage, species, tissue, physiological, and endocrinological state, and experimental conditions. In particular, ergoline alkaloids have been shown to have the significant affinity towards the 5-HT1 and 5-HT2 serotonin receptors, D1 and D2 dopamine receptors, and alpha-adrenergic receptors. This can result in a number of different effects, including vasoconstriction, convulsions, and hallucinations. (A2914, A2915, A2916)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类无致癌性（未列入国际癌症研究机构IARC清单）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

摄入麦角生物碱已知会导致麦角中毒。麦角中毒有两种形式，坏疽型和抽搐型，这很可能取决于存在的麦角生物碱的不同种类和数量。

Ingestion of ergoline alkaloids is known to cause the disease ergotism. Ergotism occurs in two forms, gangrenous and convulsive, likely depending on the different kinds and amounts of ergoline alkaloids present. (A2913)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

口服、皮肤、吸入和 parenteral（被污染的药物）。 (A3101)

Oral, dermal, inhalation, and parenteral (contaminated drugs). (A3101)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

痉挛性麦角中毒可以引起痛苦的抽搐和痉挛、腹泻、感觉异常、瘙痒、头痛、恶心和呕吐。通常胃肠道效应先于中枢神经系统效应。除了抽搐，还可能伴有幻觉和精神效应，包括躁狂或精神分裂症。坏疽性麦角中毒由于在血液循环较差的远端结构中引起的血管收缩，如手指和脚趾，从而导致干性坏疽。症状包括脱皮、周围脉搏微弱、周围感觉丧失、水肿，最终导致受影响组织的死亡和脱落。

Convulsive ergotism can cause painful seizures and spasms, diarrhea, paresthesias, itching, headaches, nausea and vomiting. Usually the gastrointestinal effects precede the central nervous system effects. As well as seizures there can be hallucinations and mental effects including mania or psychosis. Gangrenous ergotism causes dry gangrene as a result of vasoconstriction induced in the more poorly vascularized distal structures, such as the fingers and toes. Symptoms include desquamation, weak periphery pulse, loss of peripheral sensation, edema and ultimately the death and loss of affected tissues. (L1920)

来源:Toxin and Toxin Target Database (T3DB)

反应信息

• 作为反应物：
  描述：

  2',5-二氯-2'-脱氧胞苷 、 溴化氰 生成 (6aR,9R,10aS)-9-methyl-6,6a,8,9,10,10a-hexahydro-4H-indolo[4,3-fg]quinoline-7-carbonitrile
  参考文献：
  名称：

  KREPELKA, J.;SEMONSKY, M.;REZABEK, K.;SEDA, M.

  摘要：

  DOI：
• 作为产物：
  描述：

  野麥鹼 在 sodium 、 正丁醇 作用下， 生成 2',5-二氯-2'-脱氧胞苷
  参考文献：
  名称：

  Yamatodani; Abe, Journal of the Agricultural Chemical Society of Japan, 1956, vol. 20, p. 95

  摘要：

  DOI：

文献信息

• Total Syntheses of Festuclavine, Pyroclavine, Costaclavine, <i>epi</i>-Costaclavine, Pibocin A, 9-Deacetoxyfumigaclavine C, Fumigaclavine G, and Dihydrosetoclavine
  作者：Haichao Liu、Xiwu Zhang、Dong Shan、Mallesham Pitchakuntla、Yongfan Ma、Yanxing Jia

  DOI：10.1021/acs.orglett.7b01504

  日期：2017.6.16

  total synthesis of eight ergot alkaloids is reported. The approach allows the first total syntheses of pyroclavine, pibocin A, 9-deacetoxyfumigaclavine C, and fumigaclavine G and also enables the efficient synthesis of festuclavine, costaclavine, epi-costaclavine, and dihydrosetoclavine. The main feature of the synthesis is the use of an unprecedented Pd-catalyzed intramolecular Larock indole annulation/Tsuji–Trost

  报道了八种麦角生物碱的不同总合成的新方法。该方法允许pyroclavine的第一全合成，pibocin A，9-deacetoxyfumigaclavine C，和fumigaclavine G和也使羊茅，costaclavine，可以有效地合成外延-costaclavine，和dihydrosetoclavine。合成的主要特征是使用前所未有的Pd催化的分子内Larock吲哚环化/ Tsuji-Trost烯丙基化级联反应一步一步组装四环核。
• Total syntheses of clavine alkaloids by an intramolecular nitrone-olefin cycloaddition reaction
  作者：W. Oppolzer、J.I. Grayson、H. Wegmann、M. Urrea

  DOI：10.1016/s0040-4020(01)88608-7

  日期：——

  costaclavine (6), via the same isoxazolidine 18 are described. The key step 16→18 (Scheme 4) involves a transient nitrone 17 which undergoes a kinetically controlled, regio- and stereoselective intramolecular cycloaddition to a 1,2-disubstituted olefinic bond.

  外消旋麦角生物碱Chaclaclavine I（1）和6,7-secoagroclavine（4）是由吲哚-4-羧醛（7）立体选择性合成的，总收率分别为14％和13％。描述了通过相同的异恶唑烷18进一步合成异十二烷I（2），pa烯（5）和肋cost（6）的方法。关键步骤16 → 18（方案4）涉及一个瞬态硝酮17，该硝酮经历了一个动力学控制的，区域和立体选择性的分子内环内加成至1,2-二取代的烯烃键的过程。
• Using the Pummerer Cyclization−Deprotonation−Cycloaddition Cascade of Imidosulfoxides for Alkaloid Synthesis
  作者：Albert Padwa、Todd M. Heidelbaugh、Jeffrey T. Kuethe

  DOI：10.1021/jo9915729

  日期：2000.4.1

  opening and formation of a 5-acetoxy-substituted 2(1H)-pyridone. This six-ring heterocyclic system constitutes a valuable building block for the synthesis of a variety of pyridine, quinolizidine, and clavine alkaloids. The cyclization-deprotonation-cycloaddition cascade has been successfully applied to the synthesis of the naturally occurring alkaloids onychnine, dielsiquinone, (+/-)-lupinine, (+/-)-anagyrine

  带有束缚的链烯基的亚氨基亚砜的Pummerer反应已用于几种生物碱的合成。通过将适当的酰胺与（乙基亚硫基）乙酰氯加热，然后将高碘酸钠氧化，可以轻松获得级联序列所需的亚氨基亚砜。通过用乙酸酐和对甲苯磺酸处理亚氨基亚砜而获得的最初形成的硫鎓离子与相邻的亚氨基基团反应，随后生成的氧鎓离子经历去质子化反应，生成异丁香酮偶极。该中离子甜菜碱中间体经过相邻的pi键易发生分子内偶极环加成反应。将所得的环加合物暴露于另外的乙酸酐中导致开环并形成5-乙酰氧基取代的2（1H）-吡啶酮。这种六环杂环系统构成了合成各种吡啶，喹喔啉和锁骨生物碱的有价值的组成部分。环化-去质子化-环加成级联反应已成功地应用于天然存在的生物碱on药碱，地西醌，（+/-）-羽扇豆碱，（+/-）-anagyrine，（+/-）-pumiliotoxin C和（ +/-）-肋骨
• Total Synthesis of Optically Active Costaclavine. Synthetic Studies of Indoles and Related Compounds. Part 48.
  作者：Kumi OSANAI、Yuusaku YOKOYAMA、Kazuhiro KONDO、Yasuoki MURAKAMI

  DOI：10.1248/cpb.47.1587

  日期：——

  The first total synthesis of optically active costaclavine (18), an ergot alkaloid, was accomplished starting from methyl [4R-(Z)]-[4-[[(1, 1-dimethylethoxy)carbonyl]methylamino]-3, 4-dihydro-1-[(4-methylphenyl)sulfonyl]-benz[cd]indol-5(1H)-ylidene]acetate (8), which was prepared by intramolecular cyclization of 1, 1-dimethylethyl[1R-(E)]-[1-[[4-bromo-1-[(4-methylphenyl)-sulfonyl]-1H-indol-3-yl]methyl]-4-carbomethoxy-2-propenyl]methylcarbamate (7) according to the method we developed earlier during the course of the total synthesis of chanoclavine-I (9).

  首次全合成光学活性的麦角生物碱哥斯达拉素 (18)，以甲基 [4R-(Z)]-[4-[[(1, 1-二甲基乙氧基)羰基]甲基氨基]-3, 4- 为原料完成。二氢-1-[(4-甲基苯基)磺酰基]-苯并[cd]吲哚-5(1H)-亚基]乙酸酯(8)，由1, 1-二甲基乙基[1R-(E)]分子内环化制备-[1-[[4-溴-1-[(4-甲基苯基)-磺酰基]-1H-吲哚-3-基]甲基]-4-甲甲氧基-2-丙烯基]甲基氨基甲酸酯(7)根据我们的方法在 chanoclavine-I 的全合成过程中较早发展起来 (9)。
• Ninomiya, Ichiya; Kiguchi, Toshiko; Naito, Takeaki, Journal of the Chemical Society. Perkin transactions I, 1980, p. 208 - 211
  作者：Ninomiya, Ichiya、Kiguchi, Toshiko、Naito, Takeaki

  DOI：——

  日期：——