(+/-)-nantenine | 42971-15-3

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 阿朴菲
• 英文名称: (+/-)-nantenine
• 英文别名: Nantenin；O-Methyl-domesticin；18,19-dimethoxy-13-methyl-5,7-dioxa-13-azapentacyclo[10.7.1.02,10.04,8.016,20]icosa-1(20),2,4(8),9,16,18-hexaene
• CAS: 42971-15-3
• 化学式: C₂₀H₂₁NO₄
• 分子量: 339.391
• InChiKey: WSVWKHTVFGTTKJ-UHFFFAOYSA-N

物化性质

• 熔点：
  139-140 °C(Solv: ethanol (64-17-5))
• 沸点：
  487.5±45.0 °C(Predicted)
• 密度：
  1.266±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  40.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (+/-)-nantenine 在 二对甲苯酰基-L-酒石酸 、 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 以30%的产率得到O-甲基南天竹碱
  参考文献：
  名称：

  Synthetic studies and pharmacological evaluations on the MDMA (‘Ecstasy’) antagonist nantenine

  摘要：

  The naturally occurring aporphine alkaloid nantenine, has been shown to antagonize behavioral and physiological effects of MDMA in mice. We have synthesized (+/-)-nantenine via an oxidative cyclization reaction with PIFA and evaluated its binding profile against a panel of CNS targets. To begin to understand the importance of the chiral center of nantenine with regards to its capacity to antagonize the effects of MDMA in vivo, (R)- and (S)-nantenine were prepared and evaluated in a food-reinforced operant task in rats. Pretreatment with either nantenine enantiomer (0.3 mg/kg ip) completely blocked the behavioral suppression induced upon administration of 3.0 mg/kg MDMA. (+/-)-Nantenine displayed high affinity and selectivity for the alpha(1A) adrenergic receptor among several other receptors suggesting that this alpha(1) subtype may be significantly involved in the anti-MDMA effects of the enantiomers. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2009.11.053
• 作为产物：
  描述：

  6,7-dimethoxy-1-(3',4'-methylenedioxybenzyl)-2-methyl-1,2,3,4-tetrahydroisoquinoline 在 三氟化硼乙醚 、 [双(三氟乙酰氧基)碘]苯 作用下， 以76%的产率得到(+/-)-nantenine
  参考文献：
  名称：

  流动条件控制的网状生物碱发散氧化环化为阿吗啡和吗啡二酮天然产物

  摘要：

  我们描述了一种使用高价碘化合物将网状生物碱仿生氧化环化为阿吗啡和吗啡二烯酮天然产物的发散连续流动方法。

  DOI：

  10.1002/ejoc.202200301

文献信息

• A new synthesis of the aporphine alkaloids (.+-.)-glaucine and(.+-.)-nantenine.
  作者：Yutaka OZAKI、Sang-Won KIM

  DOI：10.1248/cpb.39.1349

  日期：——

  (±)-Glaucine and (±)-nantenine were newly synthesized by aromatization of cyclohexenone derivatives which were prepared by [3C+3C] condensation of two units, 1, 1-bis(ethylthio)-2-propanone and the Mannich base.

  (±)-Glaucine 和 (±)-nantenine 是通过对环己酮衍生物进行芳香化而新合成的，环己酮衍生物是由 1, 1-双（乙硫基）-2-丙酮和曼尼希碱两个单元通过[3C+3C]缩合而制备的。
• A New Synthesis of the Aporphine Alkaloids (.+-.)-Glaucine and (.+-.)-Nantenine. Application of (3C+3C) Annelation to the D-Ring Formation.
  作者：Yutaka OZAKI、Ayako KUBO、Sang-Won KIM

  DOI：10.1248/cpb.41.481

  日期：——

  A [3C + 3C] annelation using 1, 1-bis(ethulthio)-2-propanone was applied to a new synthesis of the aporphine alkaloids. Condensation of the ketone with the Mannich base gave two isomeric cyclohexenones, which were converted into the aporphine framework by aromatization. (±)-Glaucine and (±)-nantenine were prepared by employing this new aromatic synthesis.

  使用 1, 1-双（乙硫基）-2-丙酮进行的[3C + 3C]环化反应被应用于一种新的卟吩生物碱的合成。酮与曼尼希碱缩合后得到两个异构环己烯酮，通过芳香化作用将其转化为卟吩框架。通过这种新的芳香合成法，制备出了 (±)-Glaucine 和 (±)-nantenine 。
• Application of the Hypervalent Iodine Reagent to the Synthesis of Some Pentasubstituted Aporphine Alkaloids
  作者：Somsak Ruchirawat、Ratchanok Pingaew

  DOI：10.1055/s-2007-985596

  日期：2007.9

  unifying mechanism of the reaction illustrating the requirement of the P- P coupling via the six-membered transition state as the -initial step. The finding was applied to the synthesis of some pentasubstituted aporphine alkaloids.

  通过高价碘试剂研究了各种 N-取代的 1-苄基四氢异喹啉与相应的阿朴啡的氧化联芳基偶联。该研究阐明了反应的统一机制，说明了通过六元过渡态作为初始步骤的 P-P 偶联的要求。这一发现被应用于一些五取代的阿朴啡生物碱的合成。
• Studies on tetrahydroisoquinolines. IX. The synthesis of (.+-.)-domesticine and a related (.+-.)-homoaporphine via p-quinol acetates.
  作者：OSAMU HOSHINO、HIROSHI HARA、NOBUAKI SERIZAWA、BUNSUKE UMEZAWA

  DOI：10.1248/cpb.23.2048

  日期：——

  Acid (conc. H2SO4-Ac2O) treatment of the p-quinol acetate derived from (±)-1, 2, 3, 4-tetrahydro-7-hydroxy-6-methoxy-2-methyl-1-(3', 4'-methylenedioxy-benzyl or -phenethyl)-isoquinoline (VIII or IX) gave the corresponding 1-monoacetoxy-and 1, 4-diacetoxy-aporphine (XIX, XXa, and XXb) or-homoaporphine (XXIII and XXIV), respectively. Hydrolysis of XIX afforded (±)-domesticine (VI).

  酸（conc.H2SO4-Ac2O）处理由(±)-1，2，3，4-四氢-7-羟基-6-甲氧基-2-甲基-1-(3'，4'-亚甲二氧基-苄基或-苯乙基)-异喹啉（VIII 或 IX）衍生的对喹啉乙酸酯，分别得到相应的 1-单乙酰氧基和 1，4-二乙酰氧基-卟吩（XIX，XXa 和 XXb）或高卟吩（XXIII 和 XXIV）。XIX 的水解产物是 (±)- Domesticine (VI)。
• A novel synthesis of aporphine alkaloids via o-quinol acetates.
  作者：OSAMU HOSHINO、MINORU OHTANI、BUNSUKE UMEZAWA

  DOI：10.1248/cpb.26.3920

  日期：——

  Lead tetraacetate oxidation of 1-(3', 4'-dimethoxy- or 3', 4'-methylenedioxy-benzyl)-6-hydroxy-7-methoxy-2-methyl-1, 2, 3, 4-tetrahydroisoquinoline (1a or 1b) in CH2Cl2 was found to give quantitatively a diastereomeric mixture (1 : 1) of an o-quinol acetate (2a or 2b), treatment of which with Ac2O-conc. H2SO4 at room temperature led to (±)-O-acetyl-predicentrine (5a) or -isodomesticine (5b). Furthermore, hydrolysis of 5a or 5b with 1.7% KOH-MeOH afforded (±)-predicentrine (6a) or (±)-isodomesticine (6b).

  在 CH2Cl2 中，1-(3', 4'-dimethoxy- or 3', 4'-methylenedioxy-benzyl)-6-hydroxy-7-methoxy-2-methyl-1, 2, 3, 4-tetrahydroisoquinoline (1a or 1b) 的四乙酸铅氧化被发现定量地得到邻喹醇乙酸酯（2a 或 2b）的非对映体混合物（1 : 1）。H2SO4 在室温下处理，可得到(±)-O-乙酰基-redicentrine (5a) 或-isodomesticine (5b)。此外，用 1.7% KOH-MeOH 水解 5a 或 5b，可得到 (±)-predicentrine (6a) 或 (±)-isodomesticine (6b)。

表征谱图