十六基甲基甘油 | 96960-92-8

• 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: 十六基甲基甘油
• 英文名称: 1-O-hexadecyl-2-O-methyl-sn-glycerol
• 英文别名: (2S)-3-hexadecoxy-2-methoxypropan-1-ol
• CAS: 96960-92-8
• 化学式: C₂₀H₄₂O₃
• 分子量: 330.552
• InChiKey: XAWCMDFDFNRKGK-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  23
• 可旋转键数：
  19
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 储存条件：
  -20°C，密闭保存，置于干燥处

制备方法与用途

十六烷基-2-甲氧基-sn-甘油（PMG）是一种生物化学试剂，可用于生命科学相关研究中的生物材料或有机化合物。

反应信息

• 作为反应物：
  描述：

  十六基甲基甘油 在 三氟甲磺酸三甲基硅酯 、 3 A molecular sieve 、 氨 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 0.42h， 生成 (2R,3R,4R,5R,6R)-2-[(2R)-3-hexadecoxy-2-methoxypropoxy]-4,5-bis(phenylmethoxy)-6-(phenylmethoxymethyl)oxan-3-ol
  参考文献：
  名称：

  Synthesis and Growth Inhibitory Properties of Glycosides of 1-O-Hexadecyl-2-O-methyl-sn-glycerol, Analogs of the Antitumor Ether Lipid ET-18-OCH₃ (Edelfosine)

  摘要：

  Glycosylated antitumor ether lipids (GAELs), analogs of 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (1, ET-18-OCH3, edelfosine), were synthesized in good overall yields by glycosylation of 1-O-alkyl-2-O-methyl-sn-glycerol and tested for in vitro antineoplastic activity against a variety of murine and human tumor cell lines. Stereospecific glycosylation was achieved by the use of 2-O-acetyl-3,4,6-tri-O-benzylglucopyranosyl and -mannopyranosyl trichloroacetimidates as donors, with trimethylsilyl trifluoromethanesulfonate as catalyst in the presence of molecular sieves at -78 degrees C. The GAELs differ from 1 in having the sn-3-phosphocholine residue replaced by one of the following monosaccharide residues: beta- and alpha-2-deoxy-D-arabino-hexopyranosyl, alpha-D-mannopyranosyl, 2-O-methyl-beta-D-glucopyranosyl, and 2-O-methyl-alpha-D-mannopyranosyl. 1-O-Hexadecyl-2-O-methyl-3-O-(2'-deoxy-beta-D-arabino-hexopyranosyl)-sn-glycerol (2) was more effective than 1 in inhibiting the growth of MCF-7 (human breast cancer) and its adriamycin-resistant form MCF-7/adriamycin, and murine Lewis lung cancer. cells. 2-Deoxy-beta-D-arabino-hexopyranoside 2 was also an effective growth inhibitor of two drug-resistant leukemic cell lines, P388/Adr and L1210/vmdr.

  DOI：

  10.1021/jm960164j
• 作为产物：
  描述：

  1-十六烷醇 在 三氟化硼乙醚 、 四丁基氟化铵 、 sodium hydride 作用下， 以 四氢呋喃 、 二氯甲烷 、 苯 为溶剂， 反应 38.0h， 生成 十六基甲基甘油
  参考文献：
  名称：

  Regiospecific opening of glycidyl derivatives mediated by boron trifluoride. Asymmetric synthesis of ether-linked phospholipids

  摘要：

  DOI：

  10.1021/jo00280a034

文献信息

• [EN] GLYCOSYLATED ANTITUMOR ETHER LIPIDS AS NOVEL CANCER STEM CELL CYTOTOXIC AGENTS<br/>[FR] ÉTHER-LIPIDES ANTICANCÉREUX GLYCOSYLÉS EN TANT QUE NOUVEAUX AGENTS CYTOTOXIQUES DE CELLULES SOUCHES CANCÉREUSES
  申请人：UNIV MANITOBA

  公开号：WO2013116949A1

  公开（公告）日：2013-08-15

  Glycosylated antitumor ether lipids (GAELs) are effective cytotoxic agents against cancer stem cells. Furthermore, combining GAELs which kill cells by a caspase-independent pathway with agents that kill cells by apoptosis will lead to elimination of the differentiated tumor cells and the undifferentiated cancer stem cells leading to an elimination of the tumor and preventing recurrence.

  糖基化抗肿瘤醚脂质（GAELs）是有效的细胞毒性剂，可针对癌干细胞。此外，将通过一种与半胱氨酸蛋白酶无关的途径杀死细胞的GAELs与通过凋亡杀死细胞的药物结合，将导致消除分化的肿瘤细胞和未分化的癌干细胞，从而消除肿瘤并预防复发。
• [EN] DI- AND TRI-CATIONIC GLYCOSYLATED ANTITUMOR ETHER LIPIDS, L-GUCOSYLATED GAELS AND RHAMNOSE-LINKED GAELS AS CYTOTOXIC AGENTS AGAINST EPITHELIAL CANCER CELLS AND CANCER STEM CELLS<br/>[FR] ETHERS LIPIDIQUES ANTITUMORAUX GLYCOSYLÉS DI- ET TRICATIONIQUES, GAEL L-GLYCOSYLÉS ET GAEL LIÉS À DU RHAMNOSE UTILISABLES EN TANT QU'AGENTS CYTOTOXIQUES DIRIGÉS CONTRE DES CELLULES ÉPITHÉLIALES CANCÉREUSES ET DES CELLULES SOUCHES CANCÉREUSES
  申请人：UNIV MANITOBA

  公开号：WO2015179983A1

  公开（公告）日：2015-12-03

  Glycosylated Antitumor Ether Lipids (GAELs) kill cancer cells by a nonapoptotic pathway which is an attractive strategy to avoid resistance. To further optimize the antitumor effect, we prepared various analogs of di-, and tri-cationic GAEL analogs differing in the nature of the sugar (D-giucose or L-glucose), the anomeric linkage as well as position of the glycerolipid moiety. The di- and tri-cationic GAELs were synthesized and their in vitro anticancer properties were evaluated against drug resistant and aggressively growing cancer cell lines derived from human breast, prostate, pancreatic and ovarian cancers. The most potent dicationic GAEL analogs were also studied against cancer stem cells obtained from breast BT 474, prostate DU145 and ovarian A2780cp cell lines. Our results indicate that the number of positive charges, the position of the amino substituents and the nature of the sugar have significant effects on the anticancer activities of these compounds. The most active analog kill 50% of the cells at concentration range of 0.5-5μΜ and 90% of the cells at the concentration of 1-10μΜ depending on type of cancer cells.

  糖基化抗肿瘤醚脂质（GAELs）通过一种非凋亡途径杀灭癌细胞，这是一种吸引人的策略，可以避免抗药性。为了进一步优化抗肿瘤效果，我们制备了不同的双-和三-阳离子GAEL类似物，其糖的性质（D-葡萄糖或L-葡萄糖）、缩醛键以及甘油脂类团的位置不同。合成了双-和三-阳离子GAEL类似物，并评估了它们对人类乳腺、前列腺、胰腺和卵巢癌衍生的耐药和快速生长的癌细胞系的体外抗癌性能。最有效的双阳离子GAEL类似物也针对从乳腺BT 474、前列腺DU145和卵巢A2780cp细胞系中获得的癌干细胞进行了研究。我们的结果表明，阳离子数量、氨基取代物的位置和糖的性质对这些化合物的抗癌活性有显著影响。最活跃的类似物在浓度范围为0.5-5μΜ时杀死50%的细胞，在浓度为1-10μΜ时杀死90%的细胞，具体取决于癌细胞类型。
• Design, synthesis and evaluation of cytotoxic properties of bisamino glucosylated antitumor ether lipids against cancer cells and cancer stem cells
  作者：Makanjuola Ogunsina、Pranati Samadder、Temilolu Idowu、Gilbert Arthur、Frank Schweizer

  DOI：10.1039/c6md00328a

  日期：——

  diamino-D-gluco-based GAELs and their analogs, and screened them against a panel of human epithelial cancer cell lines and cancer stem cells. Most of the new GAEL analogs are more potent than chlorambucil, cisplatin and salinomycin. The most potent bisamine-based GAEL analogs 1, 2, 4 and 8 showed 2- to 3-fold enhanced cytotoxicity against various cancer cell lines when compared to β-GLN, indicating that the addition

  糖基化抗肿瘤醚脂质（GAEL）是一类通过非凋亡途径杀死癌细胞的两亲性抗肿瘤药。以前的研究已经表明，2-氨基-2-脱氧d -葡萄糖为基础的盖尔如α-GLN和β-GLN显示出大大改善的抗上皮癌细胞的抗肿瘤活性和干细胞。为了进一步优化生物活性，我们制备了一系列二氨基的d -葡糖基础的盖尔和它们的类似物，并筛选它们免受人类上皮癌细胞系和癌症干细胞的一个面板。大多数新的GAEL类似物比苯丁酸氮芥，顺铂和沙利霉素更有效。最有效的基于双胺的GAEL类似物1，与β-GLN相比，图2，图4和图8显示出对各种癌细胞系的细胞毒性提高了2-3倍，这表明添加第二个氨基基团增强了细胞毒性作用。活性最高的GAEL 1和4对分离自乳腺癌（BT-474）和前列腺（DU-145）细胞系的癌症干细胞的影响表明，两种GAEL抑制肿瘤球的形成并导致> 95％的损失5μM时癌症干细胞的活力 GAEL 1对BT-474癌症干细胞的活性优于沙利霉素。
• A new approach to the synthesis of ether phospholipids. Preparation of 1,2-dialkylglycerophosphorylcholines from L-glyceric acid
  作者：Suresh K Bhatia、Joseph Hajdu

  DOI：10.1016/s0040-4039(00)95704-6

  日期：1987.1

  A novel stereospecific synthesis of antitumor active ether phospholipids is reported.

  报道了抗肿瘤活性醚磷脂的新型立体有择合成。
• Replacing <scp>d</scp>-Glucosamine with Its <scp>l</scp>-Enantiomer in Glycosylated Antitumor Ether Lipids (GAELs) Retains Cytotoxic Effects against Epithelial Cancer Cells and Cancer Stem Cells
  作者：Makanjuola Ogunsina、Pranati Samadder、Temilolu Idowu、Gilbert Arthur、Frank Schweizer

  DOI：10.1021/acs.jmedchem.6b01773

  日期：2017.3.9

  retain the cytotoxic effects of the D-GAELs including the ability to kill BT-474 breast cancer stem cells (CSCs). When compared to adriamycin, cisplatin, and the anti-CSC agent salinomycin, L-GAELs display superior activity to kill cancer stem cells (CSCs). Mode of action studies indicate that L-GAELs like the D-GAELs kill cells via an apoptosis-independent mechanism that was not due to membranolytic

  我们描述了代谢惰性的基于l-氨基葡萄糖的糖基化抗肿瘤醚脂质（L-GAELs），该脂质保留了D-GAELs的细胞毒性作用，包括杀死BT-474乳腺癌干细胞（CSCs）的能力。与阿霉素，顺铂和抗CSC药物沙利霉素相比，L-GAEL具有杀死癌细胞干细胞（CSC）的优异活性。作用方式研究表明，像D-GAELs一样的L-GAELs通过细胞凋亡非依赖性机制杀死细胞，这不是由于膜溶解作用引起的。