1-O-十八烷基-2-O-甲基-rac-甘油 | 84337-43-9

• 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-O-十八烷基-2-O-甲基-rac-甘油
• 英文名称: 1-O-octadecyl-2-O-methylglycerol
• 英文别名: rac-1-O-octadecyl-2-O-methylglycerol；1-O-octadecyl-2-O-methyl-rac-glycerol；2-methoxy-3-octadecyloxy-1-propanol；1-Propanol, 2-methoxy-3-(octadecyloxy)-；2-methoxy-3-octadecoxypropan-1-ol
• CAS: 84337-43-9
• 化学式: C₂₂H₄₆O₃
• 分子量: 358.605
• InChiKey: JWBOVDKFGDXGCR-UHFFFAOYSA-N

物化性质

• 沸点：
  457.5±25.0 °C(Predicted)
• 密度：
  0.891±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.1
• 重原子数：
  25
• 可旋转键数：
  21
• 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

制备方法与用途

1-O-十八烷基-2-O-甲基-赖氨酸-甘油是一种生物化学试剂，可用于生物材料或有机化合物的研究，在生命科学领域中发挥重要作用。

反应信息

• 作为反应物：
  描述：

  1-O-十八烷基-2-O-甲基-rac-甘油 在 吡啶 、 silver carbonate 作用下， 以 水 、 苯 为溶剂， 反应 5.0h， 生成 依地福新
  参考文献：
  名称：

  Syntheses and antimicrobial activities of alkyl lysophospholipids.

  摘要：

  合成了二十七种脂肪基类溶血磷脂，并研究了它们的结构与抗微生物活性之间的关系。这些类似物在位置1的长链脂肪基和位置3的β-N取代氨乙基磷酸基的结构上有所不同，同时存在或缺失甘油基团的2-甲氧基。许多脂肪基溶血磷脂的抗微生物活性被发现远强于自然存在的溶血卵磷脂和卵磷脂，对四核变形虫W和多种真菌（包括人类病原体）具有显著的杀灭作用。最大活性出现在2-甲基-1-十四烷基甘油-3-phosphocholines中。带有更长或更短的烷基链的1-烷基-2-甲基甘油-3-phosphocholines的抗微生物活性则相对较低。用吡啶乙基取代胆碱基团的脂肪基溶血磷脂显示出强效的抗真菌活性，其效果与相应烷基的脂肪基磷酸甘油胆碱相当，但抗原虫活性较低。这两类化合物中的十四烷基同类物对皮肤癣菌表现出显著的抑制活性，与克霉唑的效果相当。相反，具有乙醇胺基团的脂肪基溶血磷脂显示出活性下降。将分子骨架从甘油改为1,3-丙二醇对活性影响较小，得到的1-烷基-2-脱氧甘油-3-phosphocholines展现出与1-烷基-2-甲基甘油-3-phosphocholines相似的抗微生物特性。

  DOI：

  10.1248/cpb.30.3260
• 作为产物：
  描述：

  鲨肝醇 在 吡啶 、 甲醇 、 氢氧化钾 、 三氟化硼 作用下， 以 二氯甲烷 为溶剂， 反应 50.0h， 生成 1-O-十八烷基-2-O-甲基-rac-甘油
  参考文献：
  名称：

  Alunni-Bistocchi; Orvietani; Ricci, Il Farmaco, 1990, vol. 45, # 5, p. 499 - 509

  摘要：

  DOI：

文献信息

• Synthesis and antitumor activity of new alkylphospholipids containing modifications of the phosphocholine moiety.
  作者：Kiyoshi UKAWA、Eiko IMAMIYA、Hiroaki YAMAMOTO、Katsutoshi MIZUNO、Akihiro TASAKA、Zen-ichi TERASHITA、Tetsuya OKUTANI、Hiroaki NOMURA、Takashi KASUKABE、Motoo HOZUMI、Ichiro KUDO、Keizo INOUE

  DOI：10.1248/cpb.37.1249

  日期：——

  New antitumor alkylglycerophospholipids, in which primarily the phosphocholine moiety of the platelet activating factor (PAF) molecule was modified, were synthesized from 1-alkyl-2-substituted glycerols by introducing polar head phosphoryl groups having methylene bridges of various lengths (from 2 to 14 carbons). They were tested for PAF agonistic activity and antitumor properties. In a series of 1-octadecyl-2-acetoacetylglycerophospholipids (1a-f), an increase in the length of the methylene bridge separating the phosphate and trimethylammonio group in the polar head side chain at position 3 of the glycerol backbone resulted in a progressive decrease in PAF agonistic activity and a characteristic change in antitumor activity against human promyelocytic leukemia cells (HL-60). Maximal potency was obtained with the compound having a decamethylene bridge (1e, IC50 value=1.5 μg/ml). Thus, alkylphospholipids possessing a decanmethylene bridge and a variety of substituents at position 2 (1g-n) were synthesized. They showed potent inhibitory activity with IC50 values ranging from 0.4 to 1.9 μg/ml, depending on the nature of the 2-substituent in the phospholipid molecule. In in vivo tests of the present series of alkylglycerophospholipids (1a-n), using mice bearing sarcoma 180 and mice with mammary carcinoma MM46 (both cells and compounds were given i.p.), 1-octadecyl-2-acetoacetyl-3-glyceryl ω-trimethylammoniodecyl phosphate (1e) showed the most potent life-prolonging effect. The structure-activity relationships are discussed.

  新型抗肿瘤烷基甘油磷脂是通过对血小板活化因子（PAF）分子中的磷酸胆碱部分进行修饰，从1-烷基-2-取代甘油中合成而得。通过引入具有不同长度（从2到14个碳）的亚甲基桥的极性头部磷酰基团进行了合成，并测试了其对PAF激动活性和抗肿瘤性质的影响。在一系列1-十八烷基-2-乙酰乙酰甘油磷脂（1a-f）中，随着甘油主链位置3处的磷酸和三甲铵基团之间的亚甲基桥长度增加，PAF激动活性逐渐降低，对人类早幼粒白血病细胞（HL-60）的抗肿瘤活性也发生了特征性变化。通过具有癸二烯桥的化合物（1e，IC50值=1.5μg/ml）获得了最大效力。因此，合成了具有癸二烯桥和在位置2具有各种取代基的烷基磷脂（1g-n）。它们表现出强烈的抑制活性，IC50值范围从0.4到1.9μg/ml，具体取决于磷脂分子中2-取代基的性质。在体内测试中，通过使用携带肉瘤180的小鼠和携带乳腺瘤MM46的小鼠（两种细胞和化合物均以腹腔途径给予），1-十八烷基-2-乙酰乙酰-3-甘油ω-三甲铵癸二烯磷酸酯（1e）表现出最强的延长寿命效果。讨论了结构-活性关系。
• Phospholipid derivatives
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US04778912A1

  公开（公告）日：1988-10-18

  Phospholipid derivatives of the formula: ##STR1## wherein R.sup.1 is a higher alkyl, acylmethyl or alkylcarbamoyl group which may be substituted by cycloalkyl; R.sup.2 is a lower alkyl which may be substituted by carboxy, formyl or lower acyl, a carbamoyl or thiocarbamoyl group which is substituted by lower alkyl, or an acetoacetyl group; R.sup.3, R.sup.4 and R.sup.5 are independently hydrogen or lower alkyl, or ##STR2## represents a cyclic ammonio group; and n represents an integer of 8 to 14, and salts thereof have antitumor activity.

  磷脂衍生物的化学式为：##STR1## 其中 R.sup.1 是较高的烷基、酰甲基或烷基氨基甲酰基团，可以被环烷基取代；R.sup.2 是较低的烷基，可以被羧基、甲酰基或较低酰基、一个被较低烷基取代的氨基甲酰基或硫代氨基甲酰基团，或一个乙酰乙酰基取代；R.sup.3、R.sup.4 和 R.sup.5 独立地是氢或较低烷基，或 ##STR2## 代表一个环状铵基；n 代表一个整数，范围为 8 到 14，以及其盐具有抗肿瘤活性。
• Nitrogen- and sulfur-containing lipid compounds their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US04845219A1

  公开（公告）日：1989-07-04

  A compound of the general formula [I]: ##STR1## wherein R.sub.1 represents a higher alkyl group or an N-(higher alkyl)carbamoyl group, R.sub.2 represents a lower alkyl group, an acyl group having at least three carbon atoms, an N-(lower alkyl)carbamoyl group, an N-(lower alkyl)thiocarbamoyl group or a benzyl group, R represents a primary, secondary or tertiary amino group or a quaternary ammonium group, x is 1 or 2, y is a number of 0, 1 or 2, and z is an integer of 2-10, or a pharmaceutically acceptable salt thereof. The novel substances have both anti-tumor activity and platelet activating factor-inhibiting property, and they are effective as an anti-tumor agent without circulatory trouble.

  通用式[I]的化合物：##STR1## 其中R.sub.1代表较高烷基基团或N-(较高烷基)氨基甲酰基团，R.sub.2代表较低烷基基团，至少有三个碳原子的酰基团，N-(较低烷基)氨基甲酰基团，N-(较低烷基)硫代氨基甲酰基团或苄基团，R代表一级、二级或三级氨基团或季铵基团，x为1或2，y为0、1或2的数字，z为2-10的整数，或其药学上可接受的盐。这些新物质既具有抗肿瘤活性又具有抑制血小板活化因子的性质，它们作为抗肿瘤药物在不引起循环问题的情况下是有效的。
• Novel alkyl phospholipid derivatives and uses thereof
  申请人：Zentaris GmbH

  公开号：EP1800684A1

  公开（公告）日：2007-06-27

  The present invention provides novel alkyl phospholipid derivatives that are useful for treating various diseases including tumors and/or pathophysiological conditions in mammals, preferably humans, that are caused by microorganisms, in particular fungi, protozoa, bacteria and/or viruses. Such alkyl phospholipids can be employed as single drugs or in the course of combination therapies, in particular for the treatment of leishmaniasis, trypanosomiasis and/or malaria.

  本发明提供了新型烷基磷脂衍生物，可用于治疗包括肿瘤和/或哺乳动物（尤其是人类）中由微生物，特别是真菌、原虫、细菌和/或病毒引起的各种疾病，这些烷基磷脂可作为单一药物或结合疗法的一部分，特别是用于治疗利什曼病、锥虫病和/或疟疾。
• Phospholipid compound
  申请人：Boehringer Mannheim GmbH

  公开号：US04492659A1

  公开（公告）日：1985-01-08

  The present invention provides phospholipids of the general formula: ##STR1## wherein X is a valency bond, an oxygen or sulphur atom or a sulfonyl, sulfinyl, phenylene, cycloaklylene, carbonylamino, aminocarbonyl, ureido or carbonyl group, R.sub.1 is a hydrogen atom or a straight-chained or branched, saturated or unsaturated aliphatic hydrocarbon radical containing up to 18 carbon atoms, which is optionally substituted one or more times by halogen, alkoxy, alkylthio, alkanesulfinyl, alkanesulfonyl, carbalkoxy or phenyl, R.sub.2 is a straight-chained or branched, saturated or unsaturated divalent aliphatic hydrocarbon radical containing up to 18 carbon atoms, which is optionally substituted one or more times by halogen, alkoxy, alkylthio, alkanesulphinyl, alkanesulphonyl, carbalkoxy or phenyl, Y is an oxygen atom or a --O--CO--O--, --O--CO--NH-- or --O--CS--NH-- group, R.sub.3 is a straight-chained or branched, saturated or unsaturated divalent aliphatic hydrocarbon radical containing 2 to 8 carbon atoms, which can also be part of a cycloalkane ring system and is optionally substituted one or more times by hydroxyl, halogen, alkylthio, alkanesulphinyl, alkanesulfonyl, nitrile, alkoxycarbonyl, carboxamido optionally substituted by alkyl radicals, cycoalkyl, optionally substituted phenyl or alkoxy, which in turn is optionally substituted by phenyl, hydroxyl, alkoxy, alkylthio, alkanesulfinyl, alkanesulfonyl, optionally acylated amino, alkoxycarbonyl, nitrile or carboxamido optionally substituted by alkyl radicals, Z is an oxygen or sulfur atom, R.sub.4 is a straight-chained or branched alkylene radical containing 2 to 5 carbon atoms and R.sub.5 is a hydrogen atom or a lower alkyl radical, with the proviso that when X is a valency bond, R.sub.1 and R.sub.2 together represent an unsubstituted, straight-chained or branched, saturated or unsaturated divalent aliphatic hydrocarbon chain containing up to 18 carbon atoms, Y, R.sub.4 and R.sub.5 have the above-given meanings and Z is an oxygen atom, R.sub.3 cannot be a propylene or 2-methylpropylene chain optionally substituted by hydroxyl, alkoxy or benzyloxy and with the proviso that when X is a valency bond, R.sub.1 and R.sub.2 together signify an alkyl radical containing up to 18 carbon atoms and substituted by halogen or phenyl, Y and Z are oxygen atoms and R.sub.4 and R.sub.5 have the above-given meanings, R.sub.3 cannot be a propylene or 2-hydroxypropylene chain; and the pharmacologically acceptable salts thereof. The invention also provides pharmaceutical compositions containing such compounds, having cancerostatic action without inducing thrombocyte aggregation.

  本发明提供一般式为：##STR1##的磷脂类化合物，其中X为价键，氧原子或硫原子，或磺酰基、亚磺酰基、苯基、环戊基、羰基氨基、氨基羰基、脲基或羰基基团，R.sub.1为氢原子或含有最多18个碳原子的直链或支链、饱和或不饱和脂肪族碳氢基团，可选地被卤素、烷氧基、烷基硫、烷基亚磺酰基、烷基磺酰基、羧基酯或苯基取代一次或多次，R.sub.2为含有最多18个碳原子的直链或支链、饱和或不饱和的二价脂肪族碳氢基团，可选地被卤素、烷氧基、烷基硫、烷基亚磺酰基、烷基磺酰基、羧基酯或苯基取代一次或多次，Y为氧原子或--O--CO--O--、--O--CO--NH--或--O--CS--NH--基团，R.sub.3为含有2到8个碳原子的直链或支链，饱和或不饱和的二价脂肪族碳氢基团，也可以是环戊烷环系统的一部分，并可选地被羟基、卤素、烷基硫、烷基亚磺酰基、烷基磺酰基、腈、烷氧基羧酰胺，可选地被烷基基团取代，环戊基、可选地取代的苯基或烷氧基取代，而烷氧基又可选地被苯基、羟基、烷氧基、烷基硫、烷基亚磺酰基、烷基磺酰基、可选酰基化的氨基、烷氧基羧酰胺、腈或可选地被烷基基团取代的羧酰胺所取代，Z为氧原子或硫原子，R.sub.4为含有2到5个碳原子的直链或支链的烷基基团，R.sub.5为氢原子或较低的烷基基团，但当X为价键时，R.sub.1和R.sub.2一起表示不被取代的、含有最多18个碳原子的直链或支链、饱和或不饱和的二价脂肪族碳氢链，Y、R.sub.4和R.sub.5具有上述给定的含义，且Z为氧原子时，R.sub.3不能是可选地被羟基、烷氧基或苯甲氧基取代的丙烯基或2-甲基丙烯基链，但当X为价键时，R.sub.1和R.sub.2一起表示含有最多18个碳原子的烷基基团，可被卤素或苯基取代，Y和Z为氧原子，R.sub.4和R.sub.5具有上述给定的含义，且R.sub.3不能是可选地被羟基取代的丙烯基或2-羟基丙烯基链；以及其药理学上接受的盐。本发明还提供含有这种化合物的药物组合物，具有抗癌作用而不会引起血小板聚集。