sodium (R)-norcarnitine | 109174-89-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物
• 英文名称: sodium (R)-norcarnitine
• 英文别名: sodium (R)-norcarnithine；sodium;(3R)-4-(dimethylamino)-3-hydroxybutanoate
• CAS: 109174-89-2
• 化学式: C₆H₁₂NO₃*Na
• 分子量: 169.156
• InChiKey: UJMHELCWVDGOLE-NUBCRITNSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -4.95
• 重原子数：
  11.0
• 可旋转键数：
  4.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  63.6
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  sodium (R)-norcarnitine 在 氢溴酸 作用下， 以 异丙醇 为溶剂， 反应 192.0h， 生成 hemipropanoylcarnitinium
  参考文献：
  名称：

  Syntheses, structures, and enzymatic evaluations of hemiacylcarnitiniums, a new class of carnitine acyltransferase inhibitors

  摘要：

  The syntheses of (2S,6R)-6-(carboxymethyl)-2-hydroxy-2,4,4-trimethylmorpholinium chloride (hemiacetylcarnitinium, HAC), (2S,6R)-6-(carboxymethyl)-2-ethyl-2-hydroxy-4,4-dimethylmorpholinium bromide (hemipropanoylcarnitinium, HPrC), and (2S,6R)-6-(carboxymethyl)-2-hydroxy-4,4-dimethyl-2-phenylmorpholinium chloride monohydrate (hemibenzoylcarnitinium, HBC) are described. The crystal structure of HAC is reported and compared with crystal structures of HPrC, HBC, carnitine.HCl, acetylcarnitine.HCl, and acetylcarnitine.HCl.H2O. HAC, HPrC, and HBC inhibit carnitine acetyltransferase (CAT) activity from multiple biological sources. The best inhibitor, HAC, has K(i) of 69 +/- 5-mu-M with rat liver peroxisomal CAT. HAC binds more strongly than the natural substrate (and isomer), acetylcarnitine. HAC also strongly inhibits, K(i) = 92 +/- 14-mu-M, CAT from rat heart mitochondria. HPrC inhibits pigeon breast CAT with a K(i) of 200 +/- 30-mu-M. HBC inhibits pigeon breast CAT, rat heart mitochondrial CAT, rat liver mitochondrial CAT, and rat liver peroxisomal carnitine octanoyltransferase (COT), with values of K(i) of 3500 +/- 500, 2400 +/- 70,1670 +/- 70, and 1100 +/- 100-mu-M, respectively. Racemic 6-(carboxymethyl)-2-hydroxy-2-pentadecyl-4,4-dimethylmorpholinium bromide (hemipalmitoylcarnitinium, HPC) strongly inhibits (K(i) = 2 +/- 0.3-mu-M) beef liver mitochondrial CPT(i). In summary, hemiacylcarnitiniums show promise as a general class of carnitine acyltransferase inhibitors.

  DOI：

  10.1021/jo00038a035

文献信息

• (+)-Hemipalmitoylcarnitinium strongly inhibits carnitine palmitoyltransferase-I in intact mitochondria
  作者：Richard D. Gandour、On Tai Leung、Anthony T. Greway、Rona R. Ramsay、Noirin Nic A Bhaird、Frank R. Fronczek、Bret M. Bellard、G. Kumaravel

  DOI：10.1021/jm00054a007

  日期：1993.1

  The reaction of the methyl ester of (R)-norcarnitine with 1-bromo-2-heptadecanone produces (+)-6-[(methoxycarbonyl)methyl]-2-pentadecyl-4,4-dimethylmorpholinium bromide, 3, which hydrolyzes to (+)-6-(carboxylatomethyl)-2-pentadecyl-4,4-dimethylmorpholinium (hemipalmitoylcarnitinium, HPC) upon treatment with aqueous sodium hydroxide. Single-crystal X-ray analyses have confirmed the structures of (+)-HPC and 3. (+)-HPC inhibits carnitine palmitoyltransferase (CPT-I) activity for the forward reaction (palmitoyl-CoA + carnitine -->) in intact mitochondria from rat heart and rat liver. (+)-HPC competitively (versus carnitine) inhibits CPT-I activity in both rat heart and liver mitochondria with K(i) = 2.8 +/- 0.5 and 4.2 +/- 0.7 muM, respectively. As one of the strongest specific inhibitors of CPT-I, HPC is a potential therapeutic agent in myocardial ischemia and Type II diabetes.