(-)-epineoclausenamide | 126720-48-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (-)-epineoclausenamide
• 英文别名: (3S,4R,5S,6S)-epi-neoclausenamide；(-)-neoclausenamide；(-)-Epi-Neoclausenamide；(3S,4R,5S)-3-hydroxy-5-[(S)-hydroxy(phenyl)methyl]-1-methyl-4-phenylpyrrolidin-2-one
• CAS: 126720-48-7
• 化学式: C₁₈H₁₉NO₃
• 分子量: 297.354
• InChiKey: WGYGSZOQGYRGIP-QZWWFDLISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  60.8
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3,4-二氢-2H-吡喃 、 (-)-epineoclausenamide 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Synthesis and activity in enhancing long-term potentiation (LTP) of clausenamide stereoisomers

  摘要：

  Clausenamide, isolated from aqueous extract of dry leaves of Clausena lansium, a Chinese folk medicine, was found to have potent activity in enhancing LTP and show nootropic activity in animal tests. In order to discovery more potent stereoisomers and to analyze the relationship of structure-activity, the synthesis of 16 (8 pairs) optically pure stereoisomers of clausenamide with four chiral centers was achieved. The results of LTP assay showed that the nootropic activity of the stereoisomers of clausenamide is closely related to the configuration of stereoisomers. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.03.018
• 作为产物：
  描述：

  (2RS,3SR)-2,3-epoxy-3-phenyl-propionic acid 在 四甲基氢氧化铵 、 aluminum isopropoxide 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 、 水 、 异丙醇 为溶剂， 反应 53.0h， 生成 (-)-epineoclausenamide
  参考文献：
  名称：

  旋光表烯克劳森胺的制备及其外消旋体的对映体分离

  摘要：

  我们利用手性试剂，如R - α-甲基苄胺和S -α-甲基苄胺，合成了旋光表皮环烯酰胺，用于拆分中间体（反式-3-苯基-环氧乙烷甲酸12)，然后是酰胺交换、环化和还原，这与之前报道的方法不同。Meerwein-Ponndorf-Verley 还原用于不对称还原新克劳塞米酮。阐明了该方法的合理还原机制。此后，研究了高效液相色谱 (HPLC) 对表新克劳森酰胺对映体的拆分。HPLC 也用于确定这些异构体的光学纯度。比较了用于分离对映异构体的两种手性固定相 (CSP)。在 298.15 K 下测试了不同的流动相组成。结果表明，当流动相由n-己烷和异丙醇（IPA）（75/25，v/v），外消旋物在Chiralcel OJ-H柱上分离，流速1.0 mL/min，波长210 nm，温度25° C。合成的 (-)-epineoclausenamide 和 (+)-epineoclausenamide 的对映体比

  DOI：

  10.1002/chir.23341

文献信息

• Highly efficient and concise synthesis of both antipodes of SB204900, clausenamide, neoclausenamide, homoclausenamide and ζ-clausenamide. Implication of biosynthetic pathways of clausena alkaloids
  作者：Luo Yang、De-Xian Wang、Qi-Yu Zheng、Jie Pan、Zhi-Tang Huang、Mei-Xiang Wang

  DOI：10.1039/b901965k

  日期：——

  The synthesis of both antipodes of N-methyl-N-[(Z)-styryl]-3-phenyloxirane-2-carboxamide (SB204900), clausenamide, neoclausenamide, homoclausenamide and ζ-clausenamide have been accomplished using (2S,3R)- and (2R,3S)-3-phenyloxirane-2-carboxamides as the starting materials, and SB204900 was found to be a common precursor to other N-heterocyclic clausena alkaloids. Mediated by Brønsted acids under different conditions, for example, SB204900 underwent efficient and diverse alkene-epoxide cyclization, enamide-epoxide cyclization and arene-epoxide cyclization reactions to produce the five-membered N-heterocyclic neoclausenamide, its 6-epimer, the six-membered N-heterocyclic homoclausenamide and the eight-membered N-heterocyclic ζ-clausenamide, respectively, in good to excellent yields. Regiospecific oxidation of neoclausenamide and its 6-epimer afforded neoclausenamidone. Enolization of neoclausenamidone in the presence of LiOH and the subsequent protonation under kinetic conditions at −78 °C led to the epimerization of neoclausenamidone into clausenamidone. Reduction of clausenamidone using NaBH4 furnished clausenamide in high yield.

  以(2S. 3R)-和(2R,3S)-3-苯基环氧乙烷-2-甲酰胺为起始原料，合成了 N-甲基-N-[(Z)-苯乙烯基]-3-苯基环氧乙烷-2-甲酰胺 (SB204900)、克劳森酰胺、新克劳森酰胺、同克劳森酰胺和 δ-克劳森酰胺的两个对位物、发现 SB204900 是其他 N-杂环克劳塞纳生物碱的常见前体。例如，在不同条件下由布氏酸介导，SB204900发生了高效、多样的烯-环氧化物环化反应、烯酰胺-环氧化物环化反应和炔-环氧化物环化反应，分别生成了五元N-杂环新氯森酰胺、其6-表聚体、六元N-杂环同氯森酰胺和八元N-杂环δ-氯森酰胺，收率从良好到极佳。新氯森酰胺及其 6-epimer 的 Regiospecific 氧化反应生成了新氯森酰胺酮。新氯硒脒酮在 LiOH 存在下发生烯醇化反应，随后在 °78 °C的动力学条件下发生质子化反应，从而使新氯硒脒酮发生表聚反应，生成克劳硒脒酮。用 NaBH4 还原克劳烯酰胺酮，可以得到高产率的克劳烯酰胺。
• The preparation of optically active epineoclausenamide and enantiomeric separation of its racemate
  作者：Yixiao Yan、Senmei Zhu、Xuna Luo、Yu Rao、Jinlong Su、Guantao He、Hansen Lin

  DOI：10.1002/chir.23341

  日期：2021.10

  of 210 nm and a temperature of 25°C. The enantiomeric ratio (e.r.) values of both the synthetic (−)-epineoclausenamide and (+)-epineoclausenamide were 1.3(+):98.7(−) and 99.3(+):0.7(−), respectively. In this study, a new synthetic route was designed with a yield of 12.3–14.1%, and a quick (8 min) effective separation method was obtained. This provides basis for pharmacological research and quality control

  我们利用手性试剂，如R - α-甲基苄胺和S -α-甲基苄胺，合成了旋光表皮环烯酰胺，用于拆分中间体（反式-3-苯基-环氧乙烷甲酸12)，然后是酰胺交换、环化和还原，这与之前报道的方法不同。Meerwein-Ponndorf-Verley 还原用于不对称还原新克劳塞米酮。阐明了该方法的合理还原机制。此后，研究了高效液相色谱 (HPLC) 对表新克劳森酰胺对映体的拆分。HPLC 也用于确定这些异构体的光学纯度。比较了用于分离对映异构体的两种手性固定相 (CSP)。在 298.15 K 下测试了不同的流动相组成。结果表明，当流动相由n-己烷和异丙醇（IPA）（75/25，v/v），外消旋物在Chiralcel OJ-H柱上分离，流速1.0 mL/min，波长210 nm，温度25° C。合成的 (-)-epineoclausenamide 和 (+)-epineoclausenamide 的对映体比
• Synthesis and activity in enhancing long-term potentiation (LTP) of clausenamide stereoisomers
  作者：Zhiqiang Feng、Xingzhou Li、Guojun Zheng、Liang Huang

  DOI：10.1016/j.bmcl.2009.03.018

  日期：2009.4

  Clausenamide, isolated from aqueous extract of dry leaves of Clausena lansium, a Chinese folk medicine, was found to have potent activity in enhancing LTP and show nootropic activity in animal tests. In order to discovery more potent stereoisomers and to analyze the relationship of structure-activity, the synthesis of 16 (8 pairs) optically pure stereoisomers of clausenamide with four chiral centers was achieved. The results of LTP assay showed that the nootropic activity of the stereoisomers of clausenamide is closely related to the configuration of stereoisomers. (C) 2009 Elsevier Ltd. All rights reserved.