3-carboxy-(2R)-[[hydroxy[(tetradecyl)oxy]phosphinyl]-oxy]-N,N,N-trimethyl-1-propanaminium hydroxide

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 3-carboxy-(2R)-[[hydroxy[(tetradecyl)oxy]phosphinyl]-oxy]-N,N,N-trimethyl-1-propanaminium hydroxide
• 英文别名: (3R)-3-[hydroxy(tetradecoxy)phosphoryl]oxy-4-(trimethylazaniumyl)butanoate
• 化学式: C₂₁H₄₄NO₆P
• 分子量: 437.557
• InChiKey: HSNUXANXVHLGQT-HXUWFJFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  29
• 可旋转键数：
  20
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  95.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  十四醇 在 2,4,6-三甲基吡啶 、 sodium periodate 、 三氯化磷 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 生成 3-carboxy-(2R)-[[hydroxy[(tetradecyl)oxy]phosphinyl]-oxy]-N,N,N-trimethyl-1-propanaminium hydroxide
  参考文献：
  名称：

  Practical Synthesis of 3-Carboxy-(2R)- [[hydroxy[(tetradecyl)oxy]phosphinyl]oxy]-N,N,N-trimethyl-1-propanaminium Hydroxide Inner Salt (CPI975):  A Carnitine Palmitoyltransferase I Inhibitor

  摘要：

  An efficient, safe, and cost-effective synthesis of 3-carboxy-(2R)[[hydroxy[(tetradecyl)oxy]phosphinyl]oxy]-N,N,N-trimethyl-1-propanaminium hydroxide inner salt (1, CPI975), a carnitine palmitoyltransferase I inhibitor, is described. The reaction of 1-tetradecanol (2) with stoichiometric amounts Of PCl3 in THF at -15 to -20 degreesC furnished 1-tetradecyl phosphorochloridate (3). Treatment of 3 directly with L-carnitine (7) in THF in the presence of 2,4,6.collidine afforded 8, which was oxidized with bromine to afford a crude aqueous solution of 1. Desalting was done using a cheap, stable, and recyclable resin Amberlite XAD-4. The drug substance was purified by recrystallization from a mixture of ethanol and THE The yield of 1 was 65 % with 99.7% purity. Alternatively, instead of desalting with Amberlite XAD-4 resin, 1 can be isolated by an extraction with 1-decanol, followed by precipitation with acetone and recrystallization from ethanol and THF mixture.

  DOI：

  10.1021/op020215o

文献信息

• Antidiabetic agents: a new class of reversible carnitine palmitoyltransferase I inhibitors
  作者：Robert C. Anderson、Michael Balestra、Philip A. Bell、Rhonda O. Deems、William S. Fillers、James E. Foley、James D Fraser、William R. Mann、Markus Rudin、Edwin B. Villhauer

  DOI：10.1021/jm00018a003

  日期：1995.9
• Practical Synthesis of 3-Carboxy-(2<i>R</i>)- [[hydroxy[(tetradecyl)oxy]phosphinyl]oxy]-<i>N</i>,<i>N</i>,<i>N</i>-trimethyl-1-propanaminium Hydroxide Inner Salt (CPI975):  A Carnitine Palmitoyltransferase I Inhibitor
  作者：Mahavir Prashad、John C. Amedio、Lech Ciszewski、George Lee、Carmine Villa、Kau-Ming Chen、Kapa Prasad、Oljan Repič

  DOI：10.1021/op020215o

  日期：2002.11.1

  An efficient, safe, and cost-effective synthesis of 3-carboxy-(2R)[[hydroxy[(tetradecyl)oxy]phosphinyl]oxy]-N,N,N-trimethyl-1-propanaminium hydroxide inner salt (1, CPI975), a carnitine palmitoyltransferase I inhibitor, is described. The reaction of 1-tetradecanol (2) with stoichiometric amounts Of PCl3 in THF at -15 to -20 degreesC furnished 1-tetradecyl phosphorochloridate (3). Treatment of 3 directly with L-carnitine (7) in THF in the presence of 2,4,6.collidine afforded 8, which was oxidized with bromine to afford a crude aqueous solution of 1. Desalting was done using a cheap, stable, and recyclable resin Amberlite XAD-4. The drug substance was purified by recrystallization from a mixture of ethanol and THE The yield of 1 was 65 % with 99.7% purity. Alternatively, instead of desalting with Amberlite XAD-4 resin, 1 can be isolated by an extraction with 1-decanol, followed by precipitation with acetone and recrystallization from ethanol and THF mixture.