1,2-二己酰-Sn-甘油 | 30403-47-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 甘油脂
• 中文名称: 1,2-二己酰-Sn-甘油
• 英文名称: 1,2-dihexanoyl-sn-glycerol
• 英文别名: (S)-3-hydroxypropane-1,2-diyl dihexanoate；1,2-hexanoyl-sn-glycerol；(-)-1,2-di-O-hexanoyl-sn-glycerol；(S)-2,3-bis-hexanoyloxy-propan-1-ol；[(2S)-2-hexanoyloxy-3-hydroxypropyl] hexanoate
• CAS: 30403-47-5
• 化学式: C₁₅H₂₈O₅
• 分子量: 288.384
• InChiKey: DRUFTGMQJWWIOL-ZDUSSCGKSA-N

物化性质

• 溶解度：
  DMF：20mg/mL； DMSO：7mg/mL；乙醇：>50mg/mL； PBS（pH 7.2）：0.25 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  20
• 可旋转键数：
  14
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 海关编码：
  2917190090

制备方法与用途

1,2-二己酰基-sn-甘油是一种类似蛋白激酶C(PKC)的化合物，能够激活第二信使二酰基甘油(DAG)。尽管1,2-二丙酰基-sn-甘油的生物活性尚未得到充分研究，但预计其表现与1,2-二辛酰基-sn-甘油相似。

反应信息

• 作为反应物：
  描述：

  1,2-二己酰-Sn-甘油 在 platinum(IV) oxide 、 palladium on activated charcoal 氢气 、 双氧水 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 异丙醇 为溶剂， 反应 15.25h， 生成 1,2-O-di-hexanoyl-sn-3-glycero-3-phosphothanolamine
  参考文献：
  名称：

  在人滑膜磷脂酶A2活性位点的短链磷脂类似物的底物特异性。

  摘要：

  通过制备一系列短链磷脂类似物并在远低于临界胶束浓度的条件下测量其酶解作用，研究了重组人滑液磷脂酶A2（hs-PLA2）活性位点的底物特异性。研究中使用的底物包括1,2-二己基甘油磷脂，1,2-双（烷酰基硫基）甘油磷脂和1-O-烷基-2-（烷酰基硫基）磷脂。仅观察到少量的1,2-二己酰基甘油磷脂脂质，且水解速率非常低，接近测定的检测极限。相反，选定的2-（烷酰硫基）-甘油磷脂在远低于其临界胶束浓度（cmc）的浓度下，被hs-PLA2水解得更高的速率。因此，1 2-双（己基硫基）甘油磷脂酰乙醇的ak（cat）/ K（M）= 1800 L mol-1 s-1。在计算的log P（cLogP）3-9范围内，具有直链sn-1和sn-2取代基的化合物的cLogP和log（k（cat）/ K（M）线性相关。 Sn-1醚和硫酯的水解速度相当，磷酸酯基团需要负电荷才能发挥酶的活性，sn-2取代基的不饱和度，芳香性和支链会大大减少周转率。

  DOI：

  10.1021/jm00050a009
• 作为产物：
  描述：

  己酸 在 palladium on activated charcoal 4-二甲氨基吡啶 、 氢气 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醇 、 二氯甲烷 、 溶剂黄146 为溶剂， 反应 10.0h， 生成 1,2-二己酰-Sn-甘油
  参考文献：
  名称：

  General Method for the Synthesis of Phospholipid Derivatives of 1,2-O-Diacyl-sn-Glycerols

  摘要：

  An efficient phosphite coupling protocol is described for the syntheses of the major classes of phospholipids that are derived from 1,2-O-diacyl-sn-glycerols and analogues thereof. The symmetrical diacyl glycerols 10c,d were prepared by straightforward acylation of 3-O-benzyl-sn-glycerol (7) with the appropriate carboxylic acid in the presence of dicyclohexylcarbodiimide (DCC) and 4-(dimethylamino)pyridine (DMAP). A simple method for preparing saturated and unstaturated mixed 1,2-O-diacyl-sn-glycerols was then devised that involved stepwise acylation of 7 with different alkyl carboxylic acids and debenzylation this procedure is exemplified by the preparation of 10a,b. The 1,2-O-diacyl-sn-glycerols 10a-d were then coupled with suitably protected lipid head groups employing reactive alkyl or aryl dichlorophosphites to give intermediate phosphite triesters in high overall yields. Oxidation or sulfurization of these phosphites proceeded smoothly to give the corresponding phosphate or phosphorothioate triesters, deprotection of which then provided the phosphatidylcholines 16 and 17, the phosphatidylethanolamine 20, the phosphatidylserine 28, and the phosphatidylinositols 37 and 38. Preparation of 37 and 38 required the invention of an improved method for resolving the isopropylidene-protected D-myo-inositol derivative 33. This phosphite coupling procedure was modified to assemble phospholipids bearing-polyunsaturated acyl side chains at the sn-2-position as exemplified by the preparation of the phosphatidylethanolamine 26. The one-pot phosphite coupling procedure is also applicable to the syntheses of a variety of other biologically interesting phospholipid analogues. For example, the phosphatidylinositol analogues 49-51, in which the hydroxyl group at C(2) of the inositol ring has been modified, were prepared in excellent overall yields by conjoining the 1,2-O-diacyl-sn-glycerol 10c with the protected inositol derivatives 44, 45, and 48. Phospholipid analogues that contain other replacements of the phosphate group including phosphoramidates and thiophosphates maybe prepared as evidenced by the syntheses of 56 and 61 in which the sn-3 oxygen atom of the 1,2-O-diacyl-sn-glycerol moiety is replaced with an N-benzyl group or a sulfur atom, respectively.

  DOI：

  10.1021/jo00096a023

文献信息

• Synthesis and biological evaluation of phosphatidylinositol phosphate affinity probes
  作者：Stuart J. Conway、James Gardiner、Simon J. A. Grove、Melloney K. Johns、Ze-Yi Lim、Gavin F. Painter、Diane E. J. E. Robinson、Christine Schieber、Jan W. Thuring、Leon S.-M. Wong、Meng-Xin Yin、Antony W. Burgess、Bruno Catimel、Phillip T. Hawkins、Nicholas T. Ktistakis、Leonard R. Stephens、Andrew B. Holmes

  DOI：10.1039/b913399b

  日期：——

  The synthesis of the complete family of phosphatidylinositol phosphate analogues (PIPs) from five key core intermediates A–E is described. These core compounds were obtained from myo-inositol orthoformate 1via regioselective DIBAL-H and trimethylaluminium-mediated cleavages and a resolution–protection process using camphor acetals 10. Coupling of cores A–E with phosphoramidites 34 and 38, derived from the requisite protected lipid side chains, afforded the fully-protected PIPs. Removal of the remaining protecting groups was achieved via hydrogenolysis using palladium black or palladium hydroxide on carbon in the presence of sodium bicarbonate to afford the complete family of dipalmitoyl- and amino-PIP analogues 42, 45, 50, 51, 58, 59, 67, 68, 76, 77, 82, 83, 92, 93, 99 and 100. Investigations using affinity probes incorporating these compounds have identified novel proteins involved in the PI3K intracellular signalling network and have allowed a comprehensive proteomic analysis of phosphoinositide interacting proteins.

  报道了从五个关键的核心中间体A-E合成完整的磷脂酰肌醇磷酸类似物（PIPs）家族的方法。这些核心化合物通过选择性DIBAL-H和三甲基铝介导的裂解以及使用樟脑乙缩醛的解析保护过程，从肌醇原甲酸1中获得。将核心A-E与从所需保护的脂质侧链衍生的磷酰胺34和38偶联，得到了完全保护的PIPs。通过使用钯黑或碳上的钯氢氧化物在碳酸氢钠存在下的氢解，去除了剩余的保护基团，得到了完整的二棕榈酰和氨基PIP类似物42、45、50、51、58、59、67、68、76、77、82、83、92、93、99和100。利用包含这些化合物的亲和探针进行的研究，鉴定了参与PI3K细胞内信号网络的新蛋白，并允许对磷脂酰肌醇相互作用蛋白进行全面的蛋白质组学分析。
• Synthesis and Kinetic Evaluation of Inhibitors of the Phosphatidylinositol-Specific Phospholipase C from <i>Bacillus cereus</i>
  作者：Stephen F. Martin、Allan S. Wagman

  DOI：10.1021/jo960850q

  日期：1996.11.15

  Substrate analogues of phosphatidylinositol (1) were synthesized and evaluated as potential inhibitors of the bacterial phosphatidylinositol-specific phospholipase C (PI-PLC) from Bacillus cereus. The chiral analogues of the water-soluble phospholipid substrate 5 were designed to probe the effects of varying the inositol C-2 hydroxyl group, which is generally believed to serve as the nucleophile in

  合成了磷脂酰肌醇（1）的底物类似物，并评估为蜡状芽孢杆菌的细菌磷脂酰肌醇特异性磷脂酶C（PI-PLC）的潜在抑制剂。水溶性磷脂底物5的手性类似物被设计成探测改变肌醇C-2羟基的作用，通常认为它通过PI-PLC在磷脂酰肌醇水解的第一步中用作亲核试剂。在类似物6-9中，磷脂酰肌醇衍生物的肌醇环上的C-2羟基以几种方式被合理地改变。肌醇环C-2处的立体化学颠倒导致了scyllo衍生物6。肌醇C-2羟基被氟取代，以产生烷基-氟代肌醇7，氢原子被取代以提供2-脱氧化合物8。C-2羟基被O-甲基化以制备甲氧基衍生物9. C-2处的天然肌醇构型保留在不可水解的二硫代磷酸酯类似物10中。然后使用D-肌醇1-（4-硝基苯基）在连续测定法中分析这些类似物对PI-PLC的抑制作用（25）作为发色底物。确定了每种磷脂酰肌醇衍生物的动力学参数，发现它们是具有K（i）的竞争性抑制剂，如下：6,0.2mM; 10，0.6毫米;
• Synthetic Approaches To Heavily Lipidated Phosphoglyceroinositides
  作者：Urs Schlueter、Jun Lu、Bert Fraser-Reid

  DOI：10.1021/ol0202161

  日期：2003.2.1

  [reaction: see text] Naturally occurring phosphoinositide glycoconjugates are equipped with varied acyl residues that are important for their biological activity and biosynthesis. This paper reports that acylation at O2 of the myo-inositol moiety can be achieved by stereocontrolled ortho ester rearrangement. Coupling to homo- or heterodiacylated glycerols was achieved via phosphoramidite methods, and exhaustive

  [反应：见正文]天然存在的磷酸肌醇糖缀合物配备有各种酰基残基，这些残基对其生物学活性和生物合成都很重要。本文报道，肌醇部分的O 2处的酰化可通过立体控制的原酸酯重排来实现。通过亚磷酰胺方法偶联至均二或杂二酰化甘油，并且通过转移氢化的详尽脱苄基作用提供了脱保护的磷酸甘油糖苷。后者可以在室温下在氯仿溶液中保存两个月以上，而肌醇酰基没有迁移。
• Positional Specificity and Stereoselectivity of a Lipase Preparation from Oat Seeds Acting on 1,2,3-Trihexanoylglycerol
  作者：Yasuhide Ota、Toshio Minesaki、Oshima Aki

  DOI：10.1271/bbb.61.166

  日期：1997.1

  Oat seed lipase was extracted with 0.01 m calcium chloride solution containing 0.5% Triton X-100 and precipitated with ammonium sulfate. The precipitate was dissolved in phosphate buffer at pH 6.0 and the supernatant was used as the lipase preparation. The lipase was very selective in the ester positions of 1,2,3-trihexanoylglycerol, hydrolyzing sn-3 most quickly, sn-1 moderately, and sn-2 hardly at all.

  燕麦种子脂肪酶用含 0.5% Triton X-100 的 0.01 m 氯化钙溶液提取，并用硫酸铵沉淀。沉淀物溶解在 pH 值为 6.0 的磷酸盐缓冲液中，上清液用作脂肪酶制剂。这种脂肪酶对 1,2,3-三己酰甘油的酯位有很强的选择性，水解 Sn-3 的速度最快，水解 sn-1 的速度一般，水解 sn-2 的速度几乎为零。
• Cardiolipin molecules and methods of synthesis
  申请人：Ahmad U. Moghis

  公开号：US20050266068A1

  公开（公告）日：2005-12-01

  The invention provides new synthetic routes for cardiolipin with different fatty acids and/or alkyl chains with varying chain length and also with or without unsaturation, particularly a short-chain cardiolipin. The methods comprise reacting a 1,2-O-sn-diacyl/1,2-O-sn-dialkyl glycerol or a 2-O-protected glycerol, with a phosphoramidite reagent or a phosphate triester to produce a protected cardiolipin, which is deprotected to prepare the short chain cardiolipin. The reaction schemes can be used to generate new variants of cardiolipin. The cardiolipin prepared by the present methods can be incorporated into liposomes, which can also include active agents such as hydrophobic or hydrophilic drugs. Such liposomes can be used to treat diseases or in diagnostic and/or analytical assays. Liposomes can also include ligands for targeting a particular cell type or specific tissue.

  本发明提供了一种合成不同脂肪酸和/或不同链长烷基的心磷脂的新合成路线，以及具有或不具有不饱和度，特别是一种短链心磷脂。该方法包括将1,2-O-sn-二酰基/1,2-O-sn-二烷基甘油或2-O-保护甘油与磷酸酰胺试剂或磷酸三酯反应以产生受保护的心磷脂，然后去保护以制备短链心磷脂。该反应方案可用于生成心磷脂的新变体。通过本方法制备的心磷脂可以被纳入到脂质体中，这些脂质体还可以包括疏水性或亲水性药物等活性剂。这样的脂质体可以用于治疗疾病或在诊断和/或分析检测中使用。脂质体还可以包括用于靶向特定细胞类型或特定组织的配体。