(R)-(3R,5R)-2,2,5-trimethyl-9-(methylamino)-9-oxononan-3-yl 2-methyl-6-oxohexanoate | 1252654-91-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (R)-(3R,5R)-2,2,5-trimethyl-9-(methylamino)-9-oxononan-3-yl 2-methyl-6-oxohexanoate
• 英文别名: palmyrolide aldehyde；[(3R,5R)-2,2,5-trimethyl-9-(methylamino)-9-oxononan-3-yl] (2R)-2-methyl-6-oxohexanoate
• CAS: 1252654-91-3
• 化学式: C₂₀H₃₇NO₄
• 分子量: 355.518
• InChiKey: QPGZDFUKWMYADC-BRWVUGGUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  25
• 可旋转键数：
  14
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  72.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-(3R,5R)-2,2,5-trimethyl-9-(methylamino)-9-oxononan-3-yl 2-methyl-6-oxohexanoate 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以0.006 g的产率得到(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 、 dimethyl sulfide borane 、 2,4,6-三氯苯甲酰氯 、 palladium on carbon 、 氢气 、 双氧水 、 silver(I) acetate 、 sodium hexamethyldisilazane 、 氯甲酸乙酯 、 三甲基乙酰氯 、 二异丁基氢化铝 、 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 、 lithium hydroxide 、 (S)-CBS 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 水 、 甲苯 、 叔丁醇 为溶剂， -78.0~20.0 ℃ 、101.33 kPa 条件下， 反应 57.5h， 生成 (R)-(3R,5R)-2,2,5-trimethyl-9-(methylamino)-9-oxononan-3-yl 2-methyl-6-oxohexanoate
  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

• 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。
• Detailed Analysis of (−)-Palmyrolide A and Some Synthetic Derivatives as Voltage-Gated Sodium Channel Antagonists
  作者：Suneet Mehrotra、Brendan M. Duggan、Rodolfo Tello-Aburto、Tara D. Newar、William H. Gerwick、Thomas F. Murray、William A. Maio

  DOI：10.1021/np500644k

  日期：2014.11.26

  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.