(1R,2S)-2-Amino-1-(2-tridecyl-cycloprop-1-enyl)-propane-1,3-diol | 439098-81-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (1R,2S)-2-Amino-1-(2-tridecyl-cycloprop-1-enyl)-propane-1,3-diol
• 英文别名: (1R,2S)-2-amino-1-(2-tridecylcyclopropen-1-yl)propane-1,3-diol
• CAS: 439098-81-4
• 化学式: C₁₉H₃₇NO₂
• 分子量: 311.508
• InChiKey: IXFQGNDMSNSAAU-RBUKOAKNSA-N

物化性质

• 沸点：
  466.6±45.0 °C(Predicted)
• 密度：
  0.995±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  22
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  66.5
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-硫代异氰酸辛酯 、 (1R,2S)-2-Amino-1-(2-tridecyl-cycloprop-1-enyl)-propane-1,3-diol 以 乙醚 、 乙腈 为溶剂， 反应 72.0h， 以55%的产率得到1-[(1S,2R)-2-Hydroxy-1-hydroxymethyl-2-(2-tridecyl-cycloprop-1-enyl)-ethyl]-3-octyl-thiourea
  参考文献：
  名称：

  Analogs of the dihydroceramide desaturase inhibitor GT11 modified at the amide function: synthesis and biological activities

  摘要：

  二氢酰胺去饱和酶是神经酰胺新合成中的最后一个酶。含环丙烯的鞘脂GT11是二氢酰胺去饱和酶的竞争性抑制剂。本文报告了对GT11酰胺键的化学修饰的生物学效应。N-甲基取代或将酰胺α-羰基亚甲基替换为氧会导致化合物失活。相比之下，GT11的脲化合物（3）和硫脲化合物（4）以及三种α-酮酰胺（5–7）确实抑制了N-辛酰鞘氨醇向N-辛酰神经酰胺的去饱和，尽管其效力显著低于GT11。此外，α-酮酰胺5–7也以相似的效力抑制酸性神经酰胺酶（IC50 52–83 µM）。这些化合物对中性/碱性神经酰胺酶的抑制需要约20倍的更高浓度。文中讨论了这些化合物的结构-活性关系和生物学兴趣。

  DOI：

  10.1039/b510198k
• 作为产物：
  描述：

  1,1,2-三溴-2-十三烷基环丙烷 在 2,6-二甲基吡啶 、 正丁基锂 、 三氟甲磺酸三甲基硅酯 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 2.75h， 生成 (1R,2S)-2-Amino-1-(2-tridecyl-cycloprop-1-enyl)-propane-1,3-diol
  参考文献：
  名称：

  Synthesis of a Cyclopropene Analogue of Ceramide, a Potent Inhibitor of Dihydroceramide Desaturase

  摘要：

  DOI：

  10.1002/1521-3773(20010518)40:10<1960::aid-anie1960>3.0.co;2-v

文献信息

• DIHYDROCERAMIDE DESATURASE INHIBITORS.
  申请人：CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS

  公开号：EP1354870A1

  公开（公告）日：2003-10-22

  Cyclopropenylceramide derivatives as inhibitors of desaturases characterized by the general formula I in which R1 can be an alkyl, alkenyl, alkynyl, aryl or any heterocyclic group, n can have any value and it can be branched or straight chained and can contain unsaturated carbons and R2 and R3 can have the same or different values, and it can represent aryl, heteroaryl, alkyl or acyl groups with one or more unsaturated carbons on the chain, that can be branched or straight and substituted with OH groups. Members of this new class of compounds have shown an extraordinary activity as inhibitors of the dihydroceramide desaturase and of ceramide biosynthesis and are useful for the treatment of clinical conditions associated with increased intracellular ceramide.

  环丙烯基鞘氨醇衍生物作为脱饱和酶抑制剂，其一般式为I，其中R1可以是烷基，烯基，炔基，芳基或任何杂环基团，n可以有任何值，可以是支链或直链，可以含有不饱和碳，并且R2和R3可以具有相同或不同的值，并且可以表示带有一个或多个链上不饱和碳的芳基，杂环芳基，烷基或酰基基团，可以是支链或直链，并且可以用OH基团取代。这种新类化合物的成员已经表现出极高的脱氢鞘氨醇酰酶和鞘氨醇生物合成抑制活性，并且对于治疗与细胞内鞘氨醇增加有关的临床病症非常有用。
• Dihydrosphingomyelin Impairs HIV-1 Infection by Rigidifying Liquid-Ordered Membrane Domains
  作者：Catarina R. Vieira、Jose M. Munoz-Olaya、Jesús Sot、Sonia Jiménez-Baranda、Nuria Izquierdo-Useros、Jose Luis Abad、Beatriz Apellániz、Rafael Delgado、Javier Martinez-Picado、Alicia Alonso、Josefina Casas、José L. Nieva、Gemma Fabriás、Santos Mañes、Félix M. Goñi

  DOI：10.1016/j.chembiol.2010.05.023

  日期：2010.7

  putative presence of gel domains (so) is not usually taken into account. We show that in phospholipid:sphingolipid:cholesterol mixtures, in which sphingomyelin (SM) promoted fluidlodomains, dihydrosphingomyelin (DHSM) tended to form rigid domains. Genetic and pharmacological blockade of the dihydroceramide desaturase (Des1), which replaced SM with DHSM in cultured cells, inhibited cell infection by

  细胞膜中脂质的侧向组织被认为可调节许多细胞过程。大多数研究集中在液晶（ld）和液序（lo）两个液相的共存。通常不考虑凝胶域（so）的假定存在。我们显示，在磷脂：鞘脂：胆固醇混合物中，鞘磷脂（SM）促进了流体域，二氢鞘磷脂（DHSM）倾向于形成刚性域。二氢神经酰胺去饱和酶（Des1）的遗传和药理学阻断作用是在培养细胞中用DHSM替代SM，从而抑制了具有复制能力且缺乏HIV-1的细胞感染。DHSM水平的升高产生了更坚硬的膜，从而抵抗了gp41融合肽的插入，从而抑制了病毒-细胞膜的融合。
• 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.
• Analogs of the dihydroceramide desaturase inhibitor GT11 modified at the amide function: synthesis and biological activities
  作者：Carmen Bedia、Gemma Triola、Josefina Casas、Amadeu Llebaria、Gemma Fabriàs

  DOI：10.1039/b510198k

  日期：——

  Dihydroceramide desaturase is the last enzyme in the biosynthesis of ceramide de novo. The cyclopropene-containing sphingolipid GT11 is a competitive inhibitor of dihydroceramide desaturase. The biological effects of chemical modification of the GT11 amide linkage are reported in this article. Either N-methyl substitution or replacement of the amide α-carbonyl methylene by oxygen result in inactive compounds. In contrast, both urea (3) and thiourea (4) analogs of GT11, as well as three α-ketoamides (5–7), did inhibit the desaturation of N-octanoylsphinganine to N-octanoylsphingosine, although with significantly lower potency than GT11. Furthermore, the α-ketoamides 5–7 inhibit the acidic ceramidase with similar potencies (IC50 52–83 µM). Inhibition of the neutral/alkaline ceramidase by these compounds requires around 20-fold higher concentrations. Structure–activity relationships and the biological interest of these compounds are discussed.

  二氢酰胺去饱和酶是神经酰胺新合成中的最后一个酶。含环丙烯的鞘脂GT11是二氢酰胺去饱和酶的竞争性抑制剂。本文报告了对GT11酰胺键的化学修饰的生物学效应。N-甲基取代或将酰胺α-羰基亚甲基替换为氧会导致化合物失活。相比之下，GT11的脲化合物（3）和硫脲化合物（4）以及三种α-酮酰胺（5–7）确实抑制了N-辛酰鞘氨醇向N-辛酰神经酰胺的去饱和，尽管其效力显著低于GT11。此外，α-酮酰胺5–7也以相似的效力抑制酸性神经酰胺酶（IC50 52–83 µM）。这些化合物对中性/碱性神经酰胺酶的抑制需要约20倍的更高浓度。文中讨论了这些化合物的结构-活性关系和生物学兴趣。
• Synthesis of a Cyclopropene Analogue of Ceramide, a Potent Inhibitor of Dihydroceramide Desaturase
  作者：Gemma Triola、Gemma Fabriàs、Amadeu Llebaria

  DOI：10.1002/1521-3773(20010518)40:10<1960::aid-anie1960>3.0.co;2-v

  日期：2001.5.18