N-[(2S,3R,4E)-1,3-二羟基-4-十八碳烯-2-基]二十烷酰胺 | 7344-02-7

• 物质功能分类: 有机原料 - 氨基化合物 - 酰胺类化合物
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 鞘脂
• 中文名称: N-[(2S,3R,4E)-1,3-二羟基-4-十八碳烯-2-基]二十烷酰胺
• 中文别名: C20神经酰胺
• 英文名称: N-arachidoyl-D-erythro-sphingosine
• 英文别名: N-(eicosanoyl)-sphing-4-enine；ceramide (d18:1/20:0)；ceramide C20:0；Cer (d18:1/20:0)；N-arachidoylceramide；C20-ceramide；20:0-Cer；N-icosanoylsphingosine；N-[(E,2S,3R)-1,3-dihydroxyoctadec-4-en-2-yl]icosanamide
• CAS: 7344-02-7
• 化学式: C₃₈H₇₅NO₃
• 分子量: 594.018
• InChiKey: XWBWIAOWSABHFI-NUKVNZTCSA-N

物化性质

• 熔点：
  89-90°C
• 沸点：
  646.97°C (rough estimate)
• 密度：
  0.9431 (rough estimate)
• 溶解度：
  二甲基甲酰胺：0.15mg/mL
• 物理描述：
  Solid
• 稳定性/保质期：

  在常温常压下，该物质是稳定的。

计算性质

• 辛醇/水分配系数(LogP)：
  15
• 重原子数：
  42
• 可旋转键数：
  34
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  69.6
• 氢给体数：
  3
• 氢受体数：
  3

安全信息

• 安全说明：
  S24/25

反应信息

• 作为反应物：
  描述：

  N-[(2S,3R,4E)-1,3-二羟基-4-十八碳烯-2-基]二十烷酰胺 在 palladium on barium sulfate 4 A molecular sieve 、 氢气 、 silver perchlorate 、 tin(ll) chloride 作用下， 以 四氢呋喃 为溶剂， 反应 18.5h， 生成 (2S,3R)-1-O-(α-D-galactopyranosyl)-2-(N-icosanoylamino)-1,3-octadecanediol
  参考文献：
  名称：

  Structure-Activity Relationship of .alpha.-Galactosylceramides against B16-Bearing Mice

  摘要：

  Agelasphin-9b, (2S,3S,4R)-1-O-(alpha-D-galactopyranosyl)-16-methyl-2-[N-((R)-2-hydroxytetracosanoyl)-amino]-1,3,4-heptadecanetriol, is a potent antitumor agent isolated from the marine sponge Agelas mauritianus. Various analogues of agelasphin-9b (a lead compound) were synthesized, and the relationship between their structures and biological activities was examined using several assay systems. From the results, KRN7000, (2S,3S;4R)-1-O-(alpha-D-galactopyranosyl)2-(N-hexacosanoylamino)-1,3,4-octadecanetriol, was selected as a candidate for clinical application.

  DOI：

  10.1021/jm00012a018
• 作为产物：
  描述：

  D-鞘氨醇 、 p-nitrophenyl icosanoate 在 4-二甲氨基吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 生成 N-[(2S,3R,4E)-1,3-二羟基-4-十八碳烯-2-基]二十烷酰胺
  参考文献：
  名称：

  Structure-Activity Relationship of .alpha.-Galactosylceramides against B16-Bearing Mice

  摘要：

  Agelasphin-9b, (2S,3S,4R)-1-O-(alpha-D-galactopyranosyl)-16-methyl-2-[N-((R)-2-hydroxytetracosanoyl)-amino]-1,3,4-heptadecanetriol, is a potent antitumor agent isolated from the marine sponge Agelas mauritianus. Various analogues of agelasphin-9b (a lead compound) were synthesized, and the relationship between their structures and biological activities was examined using several assay systems. From the results, KRN7000, (2S,3S;4R)-1-O-(alpha-D-galactopyranosyl)2-(N-hexacosanoylamino)-1,3,4-octadecanetriol, was selected as a candidate for clinical application.

  DOI：

  10.1021/jm00012a018

文献信息

• Synthetic Glycosphingolipids for Live-Cell Labeling
  作者：Martin Dauner、Ellen Batroff、Verena Bachmann、Christof R. Hauck、Valentin Wittmann

  DOI：10.1021/acs.bioconjchem.6b00177

  日期：2016.7.20

  insight into their localization. However, the attachment of a fluorophore to the glycan part or - more commonly - to the lipid part of glycosphingolipids is known to alter the biophysical properties and can perturb the biological function of the probe. Presented here is the synthesis of novel glycosphingolipid probes with mono and disaccharide head groups and ceramide moieties containing fatty acids of varying

  糖鞘脂是涉及许多生物学过程的细胞膜的重要组成部分。荧光标记的糖鞘脂经常用于深入了解其定位。然而，已知荧光团与糖鞘脂的聚糖部分或更通常地与脂质部分的附着会改变生物物理特性，并且会干扰探针的生物学功能。本文介绍的是具有单糖和二糖首基以及神经酰胺部分的新型糖鞘脂探针的合成，所述神经酰胺部分含有链长不同的脂肪酸（C4至C20）。这些糖鞘脂具有作为化学报告基的叠氮基或炔基，可以通过生物正交连接反应将荧光团连接至其上。可以以灵活的方式选择荧光标签和与其连接的任何接头。我们通过共聚焦显微镜技术选择性观察活细胞的质膜，证明了探针的适用性。具有较短脂肪酸的衍生物可直接应用于HEK 293T细胞，而具有较长脂肪酸的疏水性鞘糖脂可使用融合脂质体递送至细胞。
• Expression, Purification, and Characterization of a Recombinant Neutral Ceramidase from<i>Mycobacterium tuberculosis</i>
  作者：Nozomu OKINO、Rie IKEDA、Makoto ITO

  DOI：10.1271/bbb.90645

  日期：2010.2.23

  It had a pH optimum at 8.0-9.0 and quite broad specificity for various Cers. Of the Cers of different fatty acid moieties tested, those composed of C6-C24 fatty acids were well hydrolyzed, and Cers with mono unsaturated fatty acids were much more hydrolyzed than those with saturated fatty acids. Using N-dodecanoyl-7-nitrobenz-2-oxa-1,3-4-diazole (NBD)-D-erythro-sphingosine (C12-NBD-Cer) as substrates

  神经酰胺酶（CDase）催化神经酰胺（Cer）水解为鞘氨醇（Sph）和脂肪酸。我们已经报道了分枝杆菌CDase（MtCDase）的分子克隆和初步表征（J.Biol.Chem。，274，36616-36622（1999））。为了进一步确定其功能，MtCDase在大肠杆菌中表达并通过Ni-Sepharose和凝胶过滤纯化。纯化的重组酶在SDS-PAGE上显示一条条带，分子量估计为71 kDa。它的最适pH为8.0-9.0，对各种Cers具有相当广泛的特异性。在测试的不同脂肪酸部分的Cer中，由C6-C24脂肪酸组成的Cer被很好地水解，具有单不饱和脂肪酸的Cer的水解程度远高于具有饱和脂肪酸的Cer。使用N-十二烷酰基-7-硝基苯-2-氧杂-1 以3-4-二唑（NBD）-D-赤型鞘氨醇（C12-NBD-Cer）为底物，反应遵循正常的Michaelis-Menten动力学。C12-NBD-Cer的表观Km和Vmax值分别为98
• Substrate Specificity, Membrane Topology, and Activity Regulation of Human Alkaline Ceramidase 2 (ACER2)
  作者：Wei Sun、Junfei Jin、Ruijuan Xu、Wei Hu、Zdzislaw M. Szulc、Jacek Bielawski、Lina M. Obeid、Cungui Mao

  DOI：10.1074/jbc.m109.069203

  日期：2010.3

  Human alkaline ceramidase 2 (ACER2) plays an important role in cellular responses by regulating the hydrolysis of ceramides in cells. Here we report its biochemical characterization, membrane topology, and activity regulation. Recombinant ACER2 was expressed in yeast mutant cells (Delta ypc1 Delta ydc1) that lack endogenous ceramidase activity, and microsomes from ACER2-expressiong yeast cells were used to biochemically characterize ACER2. ACER2 catalyzed the hydrolysis of various ceramides and followed Michaelis-Menten kinetics. ACER2 required Ca2+ for both its in vitro and cellular activities. ACER2 has 7 putative transmembrane domains, and its amino (N) and carboxyl (C) termini were found to be oriented in the lumen of the Golgi complex and cytosol, respectively. ACER2 mutant (ACER2 Delta N36) lacking the N-terminal tail (the first 36 amino acid residues) exhibited undetectable activity and was mislocalized to the endoplasmic reticulum, suggesting that the N-terminal tail is necessary for both ACER2 activity and Golgi localization. ACER2 mutant (ACER2 Delta N13) lacking the first 13 residues was also mislocalized to the endoplasmic reticulum although it retained ceramidase activity. Overexpression of ACER2, ACER2 Delta N13, but not ACER2 Delta N36 increased the release of sphingosine 1-phosphate from cells, suggesting that its mislocalization does not affect the ability of ACER2 to regulate sphingosine 1-phosphate secretion. However, overexpression of ACER2 but not ACER2 Delta N13 or ACER2 Delta N36 inhibited the glycosylation of integrin beta 1 subunit and Lamp1, suggesting that its mistargeting abolishes the ability of ACER2 to regulation protein glycosylation. These data suggest that ACER2 has broad substrate specificity and requires Ca2+ for its activity and that ACER2 has the cytosolic C terminus and luminal N terminus, which are essential for its activity, correct cellular localization, and regulation for protein glycosylation.
• Fam57b (Family with Sequence Similarity 57, Member B), a Novel Peroxisome Proliferator-activated Receptor γ Target Gene That Regulates Adipogenesis through Ceramide Synthesis
  作者：Yzumi Yamashita-Sugahara、Yoshimi Tokuzawa、Yutaka Nakachi、Yukiko Kanesaki-Yatsuka、Masahito Matsumoto、Yosuke Mizuno、Yasushi Okazaki

  DOI：10.1074/jbc.m112.440792

  日期：2013.2

  This report identifies a novel gene encoding Fam57b (family with sequence similarity 57, member B) as a novel peroxisome proliferator-activated receptor gamma (PPAR gamma)-responsive transmembrane gene that is related to obesity. The gene was identified based on an integrated bioinformatics analysis of the following three expression profiling data sets: adipocyte differentiation of mouse stromal cells (ST2 cells), adipose tissues from obesity mice, and siRNA-mediated knockdown of Ppar gamma using ST2 cells. Fam57b consists of three variants expressed from different promoters and contains a Tram-Lag1-CLN8 domain that is related to ceramide synthase. Reporter and ChIP assays showed that Fam57b variant 2 is a bona fide PPAR gamma target gene in ST2 cells. Fam57b was up-regulated during adipocyte differentiation, suggesting that FAM57B is involved in this process. Surprisingly, FAM57B overexpression inhibited adipogenesis, and siRNA-mediated knockdown promoted adipocyte differentiation. Analysis of the ceramide content by lipid assay found that ceramides were in fact augmented in FAM57B-overexpressing ST2 cells. We also confirmed that ceramide inhibits adipogenesis. Therefore, the aforementioned results of FAM57B overexpression and siRNA experiments are reconciled by ceramide synthesis. In summary, we present in vitro evidence showing that PPAR gamma regulates Fam57b transcription during the adipogenesis of ST2 cells. In addition, our results suggest that PPAR gamma activation contributes to the regulation of ceramide metabolism during adipogenesis via FAM57B.
• ARTIFICIALLY SYNTHESIZED SPHINGOSINE DERIVATIVE LIPOID MONOMER AND USE OF SAME FOR DELIVERING NUCLEIC ACID
  申请人：INSTITUTE OF BASIC MEDICAL SCIENCES CHINESE ACADEMY OF MEDICAL SCIENCES

  公开号：US20210015767A1

  公开（公告）日：2021-01-21

  The invention provides an artificially synthesized single sphingosine lipid and use of delivering a nucleic acid thereof. More particularly, the invention provides Use or method for delivering a nucleic acid to a cell or a subject using a compound of Formula (I), a stereoisomer or a pharmaceutical acceptable salt thereof, or a combination comprising a compound of Formula (I), a stereoisomer or a pharmaceutical acceptable salt thereof,