3-O-hexadecyl-2-O-methyl-sn-glycerol | 120964-49-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 甘油脂
• 英文名称: 3-O-hexadecyl-2-O-methyl-sn-glycerol
• 英文别名: (2R)-3-hexadecoxy-2-methoxypropan-1-ol
• CAS: 120964-49-0
• 化学式: C₂₀H₄₂O₃
• 分子量: 330.552
• InChiKey: XAWCMDFDFNRKGK-HXUWFJFHSA-N

物化性质

• 熔点：
  29-30 °C
• 沸点：
  430.6±25.0 °C(Predicted)
• 密度：
  0.895±0.06 g/cm3(Predicted)

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

反应信息

• 作为反应物：
  描述：

  3-O-hexadecyl-2-O-methyl-sn-glycerol 在 草酰氯 、 sodium hydride 、 二甲基亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 diisopropyl 4-(hexadecyloxy)-3-(R)-methoxy-1-(E)-butenephosphonate
  参考文献：
  名称：

  Synthesis and Use of Novel Ether Phospholipid Enantiomers To Probe the Molecular Basis of the Antitumor Effects of Alkyllysophospholipids:  Correlation of Differential Activation of c-Jun NH₂-Terminal Protein Kinase with Antiproliferative Effects in Neuronal Tumor Cells

  摘要：

  The enantiomers of a novel unsaturated phosphonocholine antitumor ether lipid were synthesized and found to have differential antiproliferative effects against epithelial cancer cell lines. The basis of the enantioselective effects on the cells was investigated in SK-N-MC and SK-N-SH neuroblastoma tumor cells. Our results indicate that the enantioselective antiproliferative potency arises primarily from the activation of the JNK signaling pathway by the ether lipids.

  DOI：

  10.1021/jm0302748
• 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 3-O-hexadecyl-2-O-methyl-sn-glycerol
  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

• Syntheses of l-Rhamnose-Linked Amino Glycerolipids and Their Cytotoxic Activities against Human Cancer Cells
  作者：Makanjuola Ogunsina、Pranati Samadder、Temilolu Idowu、Mark Nachtigal、Frank Schweizer、Gilbert Arthur

  DOI：10.3390/molecules25030566

  日期：——

  anticancer activity. The most potent analog synthesized, 3-amino-1-O-hexadecyloxy-2R-(O–α-l-rhamnopyranosyl)-sn- glycerol 3, demonstrated a potent antitumor effect against human cancer cell lines derived from breast, prostate, and pancreas. The activity observed was superior to that observed with clinical anticancer agents including cisplatin and chlorambucil. Moreover, like other GAELs, 3 induced cell death

  成功治疗癌症的一个主要障碍是临床上可用的药物无法杀死耐药癌细胞。我们最近发现了代谢稳定的基于 l-氨基葡萄糖的糖基化抗肿瘤醚脂质 (GAEL)，它们对化疗耐药的癌细胞具有细胞毒性。在没有市售的 l-葡糖胺的情况下，合成该化合物需要很多步骤，并且总收率很低。为了克服这一限制，开发了一种使用市售 l-糖（包括 l-鼠李糖和 l-葡萄糖）的简便合成程序，并测试了 l-GAEL 的抗癌活性。合成的最有效的类似物 3-amino-1-O-hexadecyloxy-2R-(O-α-l-rhamnopyranosyl)-sn-glycerol 3，对来源于乳腺癌、前列腺癌和前列腺癌的人类癌细胞系显示出有效的抗肿瘤作用。胰腺。观察到的活性优于使用包括顺铂和苯丁酸氮芥在内的临床抗癌剂观察到的活性。此外，与其他 GAEL 一样，3 通过非膜溶解半胱天冬酶非依赖性途径诱导细胞死亡。
• Structure-Activity Relationships of Glucosamine-Derived Glycerolipids: the Role of the Anomeric Linkage, the Cationic Charge and the Glycero Moiety on the Antitumor Activity
  作者：Yaozu Xu、Makanjuola Ogunsina、Pranati Samadder、Gilbert Arthur、Frank Schweizer

  DOI：10.1002/cmdc.201200489

  日期：2013.3

  The potent antitumor activity of 1‐O‐hexadecyl‐2‐O‐methyl‐3‐O‐(2′‐amino‐2′‐deoxy‐β‐D‐glucopyranosyl)‐sn‐glycerol (1) was previously shown to arise through an apoptosis‐independent pathway. Here, a systematic structure–activity study in which the effects of the anomeric linkage, the cationic charge and the glycero moiety on the antitumor activity is described. Eight analogues of 1 were synthesized,

  1-强效的抗肿瘤活性ö十六烷基-2- ö甲基-3- Ö（2'-氨基-2'-脱氧β- - d吡喃葡萄糖基） - SN -甘油（1）中的溶液之前显示出现通过不依赖凋亡的途径。在这里，对系统的结构活性研究进行了描述，其中异头键，阳离子电荷和甘油部分对抗肿瘤活性的影响。合成了8个1的类似物，并确定了它们对乳腺癌（JIMT1和BT549），胰腺癌（MiaPaCa2）和前列腺癌（DU145，PC3）的抗肿瘤活性。1- ø十六烷基-2- ö甲基-3- Ö - （2'-氨基-2'-脱氧α-d吡喃葡萄糖基） - SN -甘油（2）一致地显示对所有五种细胞系与CC的最有效的活性50个中的6-10μ范围内的值中号。但是，用硫代糖苷键替换O-糖苷键或用叠氮化物或胍基基团替换氨基会导致效能降低三倍或更多。甘油部分也有助于1和2的总体活性，但其作用次要。对这类化合物的作用方式的研究表明，与以前的发现一致，细胞毒性作用是通过诱导大的酸性液泡而产生的。
• Structure Activity Relationships of N-linked and Diglycosylated Glucosamine-Based Antitumor Glycerolipids
  作者：Makanjuola Ogunsina、Hangyi Pan、Pranati Samadder、Gilbert Arthur、Frank Schweizer

  DOI：10.3390/molecules181215288

  日期：——

  1-O-Hexadecyl-2-O-methyl-3-O-(2'-amino-2'-deoxy-β-D-glucopyranosyl)-sn-glycerol (1) was previously reported to show potent in vitro antitumor activity on a range of cancer cell lines derived from breast, pancreas and prostate cancer. This compound was not toxic to mice and was inactive against breast tumor xenografts in mice. This inactivity was attributed to hydrolysis of the glycosidic linkage by glycosidases. Here three N-linked (glycosylamide) analogs 2–4, one triazole-linked analog 5 of 1 as well as two diglycosylated analogs 6 and 7 with different stereochemistry at the C2-position of the glycerol moiety were synthesized and their antitumor activity against breast (JIMT-1, BT-474, MDA-MB-231), pancreas (MiaPaCa2) and prostrate (DU145, PC3) cancer cell lines was determined. The diglycosylated analogs 1-O-hexadecyl-2(R)-, 3-O-di-(2'-amino-2'-deoxy-β-D-glucopyranosyl)-sn-glycerol (7) and the 1:1 diastereomeric mixture of 1-O-hexadecyl-2(R/S), 3-O-di-(2'-amino-2'-deoxy-β-D-glucopyranosyl)-sn-glycerol (6) showed the most potent cytotoxic activity at CC50 values of 17.5 µM against PC3 cell lines. The replacement of the O-glycosidic linkage by a glycosylamide or a glycosyltriazole linkage showed little or no activity at highest concentration tested (30 µM), whereas the replacement of the glycerol moiety by triazole resulted in CC50 values in the range of 20 to 30 µM. In conclusion, the replacement of the O-glycosidic linkage by an N-glycosidic linkage or triazole-linkage resulted in about a two to three fold loss in activity, whereas the replacement of the methoxy group on the glycerol backbone by a second glucosamine moiety did not improve the activity. The stereochemistry at the C2-position of the glycero backbone has minimal effect on the anticancer activities of these diglycosylated analogs.

  据先前报道，1-O-十六烷基-2-O-甲基-3-O-(2'-氨基-2'-脱氧-β-D-吡喃葡萄糖基)-sn-甘油（1）对一系列来自乳腺癌、胰腺癌和前列腺癌的癌细胞系显示出强大的体外抗肿瘤活性。该化合物对小鼠无毒性，对小鼠乳腺肿瘤异种移植无活性。这种无效性是由于糖苷酶水解了糖苷键。在此，我们合成了三种 N-连接（糖基酰胺）类似物 2-4、一种 1 的三唑连接类似物 5 以及两种在甘油分子 C2 位上具有不同立体化学结构的二糖基化类似物 6 和 7，并测定了它们对乳腺癌（JIMT-1、BT-474、MDA-MB-231）、胰腺癌（MiaPaCa2）和前列腺癌（DU145、PC3）细胞系的抗肿瘤活性。二糖基化类似物 1-O-十六烷基-2(R)-, 3-O-二（2'-氨基-2'-脱氧-β-D-吡喃葡萄糖基）-sn-甘油（7）和 1：1-O-hexadecyl-2(R/S), 3-O-di-(2'-amino-2'-deoxy-β-D-glucopyranosyl)-sn-glycerol（6）的非对映异构体混合物显示出最强的细胞毒性活性，对 PC3 细胞株的 CC50 值为 17.5 µM。用糖酰胺或糖基三唑取代 O-糖苷键，在测试的最高浓度（30 µM）下活性很小或没有活性，而用三唑取代甘油分子，CC50 值在 20 至 30 µM 之间。总之，用 N-糖苷键或三唑键取代 O-糖苷键会导致活性降低约 2 到 3 倍，而用第二个氨基葡萄糖取代甘油骨架上的甲氧基不会提高活性。甘油骨架 C2 位的立体化学对这些二糖基化类似物的抗癌活性影响很小。
• A phosphatidylinositol 3,4,5-trisphosphate analogue with low serum protein-binding affinity
  作者：Da-Sheng Wang、Ao-Lin Hsu、Ching-Shih Chen

  DOI：10.1016/s0968-0896(00)00227-3

  日期：2001.1

  Phosphatidylinositol 3,4,5-trisphosphate (PIP3) plays an important role in the regulation of diverse physiological functions. Recent evidence indicates that PIP3 is cell permeant, and can be added exogenously to modulate cellular responses. However, like many other phospholipids, PIP3 binds serum proteins with high affinity, resulting in rapid deactivation of this lipid second messenger. Our study

  磷脂酰肌醇3,4,5-三磷酸（PIP3）在调节各种生理功能中起重要作用。最近的证据表明，PIP3具有细胞渗透性，可以外源添加以调节细胞反应。但是，与许多其他磷脂一样，PIP3以高亲和力结合血清蛋白，导致该脂质第二信使迅速失活。我们的研究表明，低至10微克/毫升的牛血清白蛋白（BSA）消除了二棕榈酰-PIP3的生物活性。与血清蛋白的这种非特异性相互作用阻碍了在需要血清的生物学研究中使用PIP3。我们在这里报告一个醚连接的PIP3类似物，1-O-（1-O-十六烷基-2-O-甲基-sn-甘油-3-磷酸基）-肌醇3,4,5-三磷酸（C16Me-PIP3 ）。在保持PIP3生物学功能的同时，显示出较低的血清蛋​​白结合亲和力。C16Me-PIP3与BSA的亲和力比其二棕榈酰对应物的亲和力低两个数量级。生化数据表明，在中等水平（最高1 mg / mL）的BSA存在下，C16Me-PIP3能够刺激T细胞中的Ca2
• Method for preventing cancer metastasis
  申请人：Vandier Christophe

  公开号：US09161944B2

  公开（公告）日：2015-10-20

  The present invention relates to the use of a specific family of glycerolipid compounds of formula (I) described in the detailed description or the manufacture of a medicament for the prevention or for the treatment of cancer metastasis.

  本发明涉及使用公式（I）所描述的特定甘油脂化合物家族或制造药物，用于预防或治疗癌症转移。