Octanoic acid [(1S,2S)-1-hydroxymethyl-2-(2-tridecyl-cycloprop-1-enyl)-2-trimethylsilanyloxy-ethyl]-amide | 649767-79-3

• 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: Octanoic acid [(1S,2S)-1-hydroxymethyl-2-(2-tridecyl-cycloprop-1-enyl)-2-trimethylsilanyloxy-ethyl]-amide
• 英文别名: N-[(1S,2S)-3-hydroxy-1-(2-tridecylcyclopropen-1-yl)-1-trimethylsilyloxypropan-2-yl]octanamide
• CAS: 649767-79-3
• 化学式: C₃₀H₅₉NO₃Si
• 分子量: 509.889
• InChiKey: KEMWMEQFAAUDFO-JDXGNMNLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.45
• 重原子数：
  35
• 可旋转键数：
  24
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Octanoic acid [(1S,2S)-1-hydroxymethyl-2-(2-tridecyl-cycloprop-1-enyl)-2-trimethylsilanyloxy-ethyl]-amide 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以31%的产率得到N-[(1S,2S)-2-hydroxy-1-(hydroxymethyl)-2-(2-tridecylcycloprop-1-enyl)ethyl]octanamide
  参考文献：
  名称：

  Synthesis of Cyclopropene Analogues of Ceramide and Their Effect on Dihydroceramide Desaturase

  摘要：

  The synthesis of several analogues of the N-[(1R,2S)-2-hydroxy-1-hydroxymethyl-2-(2-tridecyl-1-cyclopropenyl)ethyl]octanamide (GT11), the first reported inhibitor of dihydroceramide desaturase, as well as their effects on this enzyme, are described. Modifications of the parent structure include variations on the cyclopropene ring, the N-acyl chain length, the configuration of the stereocenters, and the hydroxyl group at C1. The key intermediates for the synthesis are the products resulting from the addition of suitable organolithium. compounds to either Garner's aldehyde or its enantiomer. The final products are obtained by TMSTf-induced cleavage of the protecting groups and N-acylation, both under specific conditions. An alternative method for N-Boc deprotection is also reported that allows us to obtain the cyclopropene analogue of sphingosine 12a, which can be transformed into GT11 upon acylation. The procedure consists of the conversion of the Garner aldehyde addition products into the bicyclic dihydrooxazolo[3,4,0]oxazol-3-ones 19 by transesterification in basic medium of the tert-butyl group with the hydroxyl function at C3. Mild cleavage of the N,O-isopropylidene cyclic acetal present in 19 affords the oxazolidin-2-one 20, which gives 12a upon saponification. Furthermore, compound 20 is also the key intermediate in the synthesis of the terminal deoxy, methoxy, and fluoro derivatives 9, 10, and 11, respectively. Determination of dihydroceramide desaturase activity in vitro showed that GT11 was a competitive inhibitor (K-i = 6 muM) and that its analogues with N-hexanoyl (6) and N-decanoyl (7) moieties inhibited the enzyme with similar potencies (IC50 = 13 and 31 muM, respectively). No decrease in dihydroceramide desaturase activity was observed with any of the other compounds tested.

  DOI：

  10.1021/jo030141u
• 作为产物：
  描述：

  (S)-4-[Hydroxy-(2-tridecyl-cycloprop-1-enyl)-methyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester 在 2,6-二甲基吡啶 、 sodium acetate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 5.5h， 生成 Octanoic acid [(1S,2S)-1-hydroxymethyl-2-(2-tridecyl-cycloprop-1-enyl)-2-trimethylsilanyloxy-ethyl]-amide
  参考文献：
  名称：

  Synthesis of Cyclopropene Analogues of Ceramide and Their Effect on Dihydroceramide Desaturase

  摘要：

  The synthesis of several analogues of the N-[(1R,2S)-2-hydroxy-1-hydroxymethyl-2-(2-tridecyl-1-cyclopropenyl)ethyl]octanamide (GT11), the first reported inhibitor of dihydroceramide desaturase, as well as their effects on this enzyme, are described. Modifications of the parent structure include variations on the cyclopropene ring, the N-acyl chain length, the configuration of the stereocenters, and the hydroxyl group at C1. The key intermediates for the synthesis are the products resulting from the addition of suitable organolithium. compounds to either Garner's aldehyde or its enantiomer. The final products are obtained by TMSTf-induced cleavage of the protecting groups and N-acylation, both under specific conditions. An alternative method for N-Boc deprotection is also reported that allows us to obtain the cyclopropene analogue of sphingosine 12a, which can be transformed into GT11 upon acylation. The procedure consists of the conversion of the Garner aldehyde addition products into the bicyclic dihydrooxazolo[3,4,0]oxazol-3-ones 19 by transesterification in basic medium of the tert-butyl group with the hydroxyl function at C3. Mild cleavage of the N,O-isopropylidene cyclic acetal present in 19 affords the oxazolidin-2-one 20, which gives 12a upon saponification. Furthermore, compound 20 is also the key intermediate in the synthesis of the terminal deoxy, methoxy, and fluoro derivatives 9, 10, and 11, respectively. Determination of dihydroceramide desaturase activity in vitro showed that GT11 was a competitive inhibitor (K-i = 6 muM) and that its analogues with N-hexanoyl (6) and N-decanoyl (7) moieties inhibited the enzyme with similar potencies (IC50 = 13 and 31 muM, respectively). No decrease in dihydroceramide desaturase activity was observed with any of the other compounds tested.

  DOI：

  10.1021/jo030141u

文献信息

• Synthesis of Cyclopropene Analogues of Ceramide and Their Effect on Dihydroceramide Desaturase
  作者：Gemma Triola、Gemma Fabriàs、Josefina Casas、Amadeu Llebaria

  DOI：10.1021/jo030141u

  日期：2003.12.1

  The synthesis of several analogues of the N-[(1R,2S)-2-hydroxy-1-hydroxymethyl-2-(2-tridecyl-1-cyclopropenyl)ethyl]octanamide (GT11), the first reported inhibitor of dihydroceramide desaturase, as well as their effects on this enzyme, are described. Modifications of the parent structure include variations on the cyclopropene ring, the N-acyl chain length, the configuration of the stereocenters, and the hydroxyl group at C1. The key intermediates for the synthesis are the products resulting from the addition of suitable organolithium. compounds to either Garner's aldehyde or its enantiomer. The final products are obtained by TMSTf-induced cleavage of the protecting groups and N-acylation, both under specific conditions. An alternative method for N-Boc deprotection is also reported that allows us to obtain the cyclopropene analogue of sphingosine 12a, which can be transformed into GT11 upon acylation. The procedure consists of the conversion of the Garner aldehyde addition products into the bicyclic dihydrooxazolo[3,4,0]oxazol-3-ones 19 by transesterification in basic medium of the tert-butyl group with the hydroxyl function at C3. Mild cleavage of the N,O-isopropylidene cyclic acetal present in 19 affords the oxazolidin-2-one 20, which gives 12a upon saponification. Furthermore, compound 20 is also the key intermediate in the synthesis of the terminal deoxy, methoxy, and fluoro derivatives 9, 10, and 11, respectively. Determination of dihydroceramide desaturase activity in vitro showed that GT11 was a competitive inhibitor (K-i = 6 muM) and that its analogues with N-hexanoyl (6) and N-decanoyl (7) moieties inhibited the enzyme with similar potencies (IC50 = 13 and 31 muM, respectively). No decrease in dihydroceramide desaturase activity was observed with any of the other compounds tested.