tert-butyl (4S)-4-[1-hydroxyhexadec-2-ynyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate | 785828-30-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: tert-butyl (4S)-4-[1-hydroxyhexadec-2-ynyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate
• 英文别名: tert-butyl (4S)-4-(1-hydroxyhexadec-2-ynyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate
• CAS: 785828-30-0
• 化学式: C₂₆H₄₇NO₄
• 分子量: 437.663
• InChiKey: JKAJAOBVDVKBPE-NQCNTLBGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.9
• 重原子数：
  31
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (4S)-4-[1-hydroxyhexadec-2-ynyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate 在 盐酸 、 对甲苯磺酸 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 2.5h， 生成 4-十八碳炔-1,3-二醇,2-氨基-,(2S,3R)-
  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：

  1-十五炔 、 3-反-溴碳-2,2'-二甲基氧酸酯 在 正丁基锂 作用下， 以 四氢呋喃 为溶剂， 以76%的产率得到tert-butyl (4S)-4-[1-hydroxyhexadec-2-ynyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate
  参考文献：
  名称：

  3-C-甲基神经酰胺的合成

  摘要：

  我们报告了一系列 3-C-甲基神经酰胺衍生物 2a,b、12a,b、13a,b 和 14a,b 的合成。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

  DOI：

  10.1002/ejoc.200400114

文献信息

• Facile and efficient addition of terminal alkynes to benzotriazole esters: synthesis of d-erythro-sphingosine using ynones as the key intermediate
  作者：José Antonio Morales-Serna、Alejandro Sauza、Gabriela Padrón de Jesús、Rubén Gaviño、Gustavo García de la Mora、Jorge Cárdenas

  DOI：10.1016/j.tetlet.2013.10.082

  日期：2013.12

  From the perspective of synthesis, ynones are compounds of considerable interest because of their occurrence in a wide variety of biologically active molecules and as key synthetic intermediates. In this context, a facile and highly efficient synthesis of ynones was developed based on the high reactivity of benzotriazole esters formed in situ. Lithium acetylides can alkylate various carboxylic acids

  从合成的角度来看，炔酮是令人关注的化合物，因为它们存在于多种生物活性分子中，并作为关键的合成中间体。在这种情况下，基于原位形成的苯并三唑酯的高反应性，开发了一种容易且高效的炔酮合成方法。乙炔锂可将各种羧酸烷基化，收率范围为60％至92％。为了确定我们的方法是用于合成复杂的生物相关分子，我们合成D-有用赤-sphingosine四个步骤，并与L-丝氨酸33％的总收率。
• SPHINGOSINE COMPOUND, METHOD FOR PRODUCING THE SAME, AND SPHINGOMYELINASE INHIBITOR
  申请人：Nishizawa Mugio

  公开号：US20100099881A1

  公开（公告）日：2010-04-22

  An object of the invention is to provide a novel sphingosine compound with an inhibitory activity against sphingomyelinase, and a method for producing the sphingosine compound. The novel sphingosine compound or a salt thereof according to the invention is represented by Formula (1): wherein one of R 1 and R 2 is hydrogen, and the other is a group represented by Formula (G): wherein n is 0 or 1; and R 3 is hydrogen, C 1-23 alkyl, C 3-8 cycloalkyl, C 2-6 alkenyl, C 1-6 alkoxy, C 3-8 cycloalkyloxy, phenyl, or furil.

  本发明的目的是提供一种具有抑制神经鞘磷脂酶活性的新型鞘氨醇化合物和一种制备该鞘氨醇化合物的方法。根据本发明，所述新型鞘氨醇化合物或其盐由式（1）表示：其中R1和R2中的一个是氢，另一个是由式（G）表示的基团：其中n为0或1；R3为氢、C1-23烷基、C3-8环烷基、C2-6烯基、C1-6烷氧基、C3-8环烷氧基、苯基或呋喃基。
• A stereodivergent synthesis of D-erythro-sphingosine and D-threo-sphingosine from L-serine
  作者：Philip Garner、Jung Min Park、Elise Malecki

  DOI：10.1021/jo00253a039

  日期：1988.9
• US8093395B2
  申请人：——

  公开号：US8093395B2

  公开（公告）日：2012-01-10
• 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.