(-)-palmyrolide A | 1252654-90-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: (-)-palmyrolide A
• 英文别名: (3R,13R,15R,E)-15-(tert-butyl)-3,8,13-trimethyl-1-oxa-8-azacyclopentadec-6-ene-2,9-dione；Palmyrolide A；(3R,6E,13R,15R)-15-tert-butyl-3,8,13-trimethyl-1-oxa-8-azacyclopentadec-6-ene-2,9-dione
• CAS: 1252654-90-2
• 化学式: C₂₀H₃₅NO₃
• 分子量: 337.503
• InChiKey: WRIPSIKIDAUKBP-CJRSWYJFSA-N

物化性质

• 沸点：
  494.5±44.0 °C(predicted)
• 密度：
  0.935±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (-)-palmyrolide A 在 盐酸 、 sodium tetrahydroborate 、 水 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 1.0h， 生成 (R)-(3R,5R)-2,2,5-trimethyl-9-(methylamino)-9-oxononan-3-yl 6-hydroxy-2-methylhexanoate
  参考文献：
  名称：

  Detailed Analysis of (−)-Palmyrolide A and Some Synthetic Derivatives as Voltage-Gated Sodium Channel Antagonists

  摘要：

  A small library of synthetic (-)-palmyrolide A diastereomers, analogues, and acyclic precursors have been examined with respect to their interaction with voltage-gated sodium channels (VGSCs). Toward this goal, the ability of (-)-palmyrolide A and analogues to antagonize veratridine-stimulated Na(+) influx in primary cultures of mouse cerebrocortical neurons was assessed. We found that synthetic (-)-palmyrolide A and its enantiomer functioned as VGSC antagonists to block veratridine-induced sodium influx. A detailed NMR and computational analysis of four diastereomers revealed that none had the same combination of shape and electrostatic potential as exhibited by natural (-)-palmyrolide A. These data indicate that the relative configuration about the tert-butyl and methyl substituents appears to be a prerequisite for biological function. Additional testing revealed that the enamide double bond was not necessary for blocking veratridine-induced sodium influx, whereas the acyclic analogues and other macrolide diastereomers tested were inactive as inhibitors of VGSCs, suggesting that the intact macrolide was required.

  DOI：

  10.1021/np500644k
• 作为产物：
  描述：

  6-(苄氧基)-1-己醇 在 sodium chlorite 、 sodium dihydrogenphosphate 、 2-甲基-2-丁烯 、 草酰氯 、 2,4,6-三氯苯甲酰氯 、 palladium on carbon 、 氢气 、 双氧水 、 sodium hexamethyldisilazane 、 三甲基乙酰氯 、 1-羟基苯并三唑 、 二甲基亚砜 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 叔丁醇 、 苯 为溶剂， -78.0~20.0 ℃ 、101.33 kPa 条件下， 反应 109.58h， 生成 (-)-palmyrolide A
  参考文献：
  名称：

  棕榈酰化物A及其5,7- Epi异构体的全合成

  摘要：

  通过采用针对所提出的结构及其5,7- epi异构体开发的合成策略，描述了具有15个成员的神经活性大环内酯类化合物pallyrolide A的立体选择性全合成。设计该策略的方式是，可以从一次操作中获得建立棕榈酰A的绝对构型所需的一组立体异构体。外-亚甲基-γ-丁内酯的非对映选择性加氢成α-甲基-γ-丁内酯，山口酯化和分子内脱水环化形成反式-烯酰胺是合成的关键步骤。

  DOI：

  10.1016/j.tet.2013.01.048

文献信息

• Expedient Synthesis of Large-Ring<i>trans</i>-Enamide Macrolides by CuI-Mediated Intramolecular Coupling of Vinyl Iodide with Amide: Total Synthesis of Palmyrolide A
  作者：Jhillu Singh Yadav、Borra Suresh、Pabbaraja Srihari

  DOI：10.1002/ejoc.201600325

  日期：2016.5

  An efficient and improved procedure for copper-catalyzed coupling of vinyl iodide with amide in an intramolecular fashion is described. The protocol utilizes a combination of copper iodide, CsF and (±)-1,2-diaminocyclohexane as ligand. The vinyl iodide couples efficiently with the amide to generate an enamide macrolide without any alteration in the double -bond geometry. The developed method was applied

  描述了一种以分子内方式将乙烯基碘与酰胺进行铜催化偶联的有效且改进的方法。该协议使用碘化铜、CsF 和 (±)-1,2-二氨基环己烷作为配体的组合。乙烯基碘与酰胺有效偶联以生成烯酰胺大环内酯，而双键几何结构没有任何改变。所开发的方法已应用于几种大环烯酰胺大环内酯的合成，以及天然产物棕榈内酯A和同系sanctolide A的全合成。
• Evolution of a Protecting-Group-Free Total Synthesis: Studies en Route to the Neuroactive Marine Macrolide (−)-Palmyrolide A
  作者：Rodolfo Tello-Aburto、Tara D. Newar、William A. Maio

  DOI：10.1021/jo301121f

  日期：2012.7.20

  neuroactive marine macrolide (−)-palmyrolide A is described. Our first-generation approach aimed to unlock the unknown C(5)–C(7) stereochemical relationship via the synthesis of four diastereomers of palmyrolide A aldehyde, a known degradation product. When these efforts provided inconclusive results, recourse to synthesizing all possible stereocombinations of the 15-membered macrolide was undertaken.

  描述了我们对神经活性海洋大环内酯（-）-palmyrolide A的第一个全合成的合成工作的完整说明。我们的第一代方法旨在通过合成已知的降解产物Palmyrolide A醛的四种非对映异构体来解锁未知的C（5）-C（7）立体化学关系。当这些努力提供不确定的结果时，便采取了合成15元大环内酯类化合物所有可能的立体组合的方法。这些研究对于确认绝对立体化学至关重要，可以产生第一个（+）- ent- palmyrolide A的全合成。在这项工作之后，还报道了第一个无保护基的天然（-）-palmyrolide A的全合成。 。
• Stereoselective total synthesis of palmyrolide A via intramolecular trans N-methyl enamide formation
  作者：Suresh Borra、Sravanth Kumar Amrutapu、Srihari Pabbaraja、Yadav Jhillu Singh

  DOI：10.1016/j.tetlet.2016.08.054

  日期：2016.10

  The stereoselective total synthesis of palmyrolide A was accomplished through macrocyclization reaction involving trans enamide formation by coupling of vinyl iodide with secondary amide in an intramolecular fashion. The two coupling partners, vinyl iodide 4 and secondary amide 3 were synthesized from the same intermediate alcohol 5. Yamaguchi esterification and CBS-reduction are the other key steps

  棕榈酰A的立体选择性全合成是通过大环化反应完成的，该反应涉及通过将碘化乙烯与仲酰胺以分子内方式偶联而形成反式酰胺。由相同的中间体醇5合成两个碘化乙烯基偶合物4和仲酰胺3。山口酯化和CBS还原是合成中的其他关键步骤。
• Modular Total Synthesis of (–)‐Palmyrolide A and (+)‐( <scp> 5 <i>S</i> </scp> , <scp> 7 <i>S</i> </scp> )‐Palmyrolide A via <scp>Ring‐Closing</scp> Metathesis and Alkene Isomerization†
  作者：Yecai Lai、Wei‐Min Dai

  DOI：10.1002/cjoc.202000458

  日期：2021.1

  has been established for total synthesis of the naturally occurring (–)‐palmyrolide A and (+)‐5,7‐epi‐palmyrolide A. By using the racemic tert‐butyl carbinol‐containing alkyl iodide, the two diastereoisomeric macrolides could be obtained from the same sequence of reactions, demonstrating the flexibility of the multimodule assembly strategy for diverted total synthesis.

  已经建立了一种五模块组装方法，用于完全合成天然存在的（–）‐ palmyrolide A和（+）‐ 5,7 ‐ epi‐ palmyrolideA。通过使用外消旋叔丁基甲醇含有的烷基碘，这两种非对映异构体大环内酯类化合物可从相同的反应序列中获得，证明了多模块组装策略用于转移总合成的灵活性。
• Total synthesis of palmyrolide A and its 5,7-epi isomers
  作者：Gangarajula Sudhakar、Karla Janardhan Reddy、Jagadeesh Babu Nanubolu

  DOI：10.1016/j.tet.2013.01.048

  日期：2013.3

  Stereoselective total synthesis of palmyrolide A, a 15-membered neuroactive macrolide, was described by adopting a synthetic strategy developed for the proposed structures, and its 5,7-epi isomers. The strategy was designed in such a way that the set of stereoisomers, which were needed for establishing the absolute configuration of palmyrolide A, could be obtained from one time operation. The diastereoselective

  通过采用针对所提出的结构及其5,7- epi异构体开发的合成策略，描述了具有15个成员的神经活性大环内酯类化合物pallyrolide A的立体选择性全合成。设计该策略的方式是，可以从一次操作中获得建立棕榈酰A的绝对构型所需的一组立体异构体。外-亚甲基-γ-丁内酯的非对映选择性加氢成α-甲基-γ-丁内酯，山口酯化和分子内脱水环化形成反式-烯酰胺是合成的关键步骤。