dioleylglycero-ethoxy-ethoxy-ethoxy-ethanamine cyclooct-1-yn-3-glycole | 597533-73-8

• 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: dioleylglycero-ethoxy-ethoxy-ethoxy-ethanamine cyclooct-1-yn-3-glycole
• 英文别名: 2-[2-[2-[2-[2,3-bis[(Z)-octadec-9-enoxy]propoxy]ethoxy]ethoxy]ethoxy]ethanamine
• CAS: 597533-73-8
• 化学式: C₄₇H₉₃NO₆
• 分子量: 768.259
• InChiKey: JZFYJZJYNDKXPH-CLFAGFIQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  14.3
• 重原子数：
  54
• 可旋转键数：
  48
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  81.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  dioleylglycero-ethoxy-ethoxy-ethoxy-ethanamine cyclooct-1-yn-3-glycole 在 potassium carbonate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 N-(2-{2-[2-(2-{2,3-Bis-[((Z)-octadec-9-enyl)oxy]-propoxy}-ethoxy)-ethoxy]-ethoxy}-ethyl)-3-((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-hydroxymethyl-tetrahydro-pyran-2-ylsulfanyl)-propionamide
  参考文献：
  名称：

  Synthesis of an amphiphilic tetraantennary mannosyl conjugate and incorporation into liposome carriers

  摘要：

  We have synthesized a novel conjugate (Man(4)K(3)DOG) composed of a tetramannosyl head group connected, via a polyethylene glycol spacer, to a lipid moiety. This amphiphilic molecule was easily incorporated into the bilayers of liposomes. As expected from the clustering effect, such multivalent mannose residues when exposed on the surface of the vesicles showed much higher binding affinity for Concanavalin A than their monomannosyl analogue. Mannosylated liposomes prepared with the tetravalent antenna could be promising carriers for e.g., loading dendritic cells with antigens for vaccination purposes. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00472-4
• 作为产物：
  描述：

  11-azide-1-{(methylsulfonyl)oxy}-3,6,9-trioxaundecane 在 水 、 sodium hydride 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 生成 dioleylglycero-ethoxy-ethoxy-ethoxy-ethanamine cyclooct-1-yn-3-glycole
  参考文献：
  名称：

  Synthesis of an amphiphilic tetraantennary mannosyl conjugate and incorporation into liposome carriers

  摘要：

  We have synthesized a novel conjugate (Man(4)K(3)DOG) composed of a tetramannosyl head group connected, via a polyethylene glycol spacer, to a lipid moiety. This amphiphilic molecule was easily incorporated into the bilayers of liposomes. As expected from the clustering effect, such multivalent mannose residues when exposed on the surface of the vesicles showed much higher binding affinity for Concanavalin A than their monomannosyl analogue. Mannosylated liposomes prepared with the tetravalent antenna could be promising carriers for e.g., loading dendritic cells with antigens for vaccination purposes. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00472-4

文献信息

• [EN] LIPIDIC COMPOUNDS COMPRISING AT LEAST ONE TERMINAL RADICAL OF FORMULA -NH-CX-A OR -NH-CX-NH-A, COMPOSITIONS CONTAINING THEM AND USES THEREOF<br/>[FR] COMPOSÉS LIPIDIQUES COMPRENANT AU MOINS UN RADICAL TERMINAL DE FORMULE -NH-CX-A OU -NH-CX-NH-A, COMPOSITIONS LES CONTENANT ET LEURS UTILISATIONS
  申请人：SANOFI PASTEUR

  公开号：WO2022013443A1

  公开（公告）日：2022-01-20

  The disclosure relates to novel lipidic compounds, lipid nanoparticles (LNPs) containing thereof, and the use of the lipidic compounds or the LNPs for the delivery of nucleic acid. The lipidic compounds as disclosed herein comprise at least one terminal radical of formula (I): *-NH-CX-(NH)n-A (I) wherein: - *- represents a single bond linking said radical of formula (I), directly or not, to to one C10 to C55 lipophilic or hydrophobic tail-group; - n is 0 or 1; - X is an oxygen or sulfur atom, and - A represents an optionally substituted 5- or 6-membered unsaturated heterocyclic radical or 5- or 6-membered heteroaromatic ring radical, both containing at least one nitrogen atom; or one of the pharmaceutically acceptable salts of said radical of formula (I); and with said compound that is in all the possible racemic, enantiomeric and diastereoisomeric isomer forms.

  该披露涉及新型脂质化合物，含有该脂质化合物的脂质纳米颗粒（LNPs），以及利用该脂质化合物或LNPs用于传递核酸。所述的脂质化合物至少包括一个式（I）的末端基团：*-NH-CX-(NH)n-A（I）其中：- *-代表连接所述式（I）的基团的单键，直接或间接地，连接到一个C10至C55的亲脂性或疏水性尾基团；- n为0或1；- X为氧或硫原子，- A代表一个可选择地取代的含有至少一个氮原子的5-或6-成员不饱和杂环基团或5-或6-成员杂芳环基团；或所述的式（I）基团的药学上可接受的盐之一；以及与所述化合物一起，以所有可能的外消旋、对映异构体和顺反异构体形式存在。
• 一种可电离阳离子脂质的制备及其在脂质递送系统及流感血凝素mRNA疫苗中的应用
  申请人：苏州祥龙生物医药科技有限公司

  公开号：CN115105475A

  公开（公告）日：2022-09-27

  本发明公开了一种可电离阳离子脂质的制备及其在脂质递送系统及流感血凝素mRNA疫苗中的应用，涉及医药技术领域。本发明提供了一种热稳定性咪唑修饰的可电离阳离子的制备方法，以及该咪唑修饰的可电离阳离子LNP制备流感血凝素mRNA疫苗的方法与应用；该流感血凝素mRNA经核苷酸密码子优化和1‑甲基假尿苷(m1Ψ)修饰，实行自扩增和自加帽设计；并证实该方法制备的mRNA‑LNP流感预防疫苗明显增加稳定性和提高免疫效能。本发明合成的热稳定性咪唑修饰的可电离阳离子LNP极大地解决了现有mRNA疫苗的超低温保存及冷链运输问题，并为流感的临床预防和应用提供了新的血凝素mRNA疫苗制备方法。
• Smart tools and orthogonal click-like reactions onto small unilamellar vesicles
  作者：Christophe Salomé、Maria Vittoria Spanedda、Benoit Hilbold、Etienne Berner、Béatrice Heurtault、Sylvie Fournel、Benoit Frisch、Line Bourel-Bonnet

  DOI：10.1016/j.chemphyslip.2015.03.004

  日期：2015.5

  Click-based reactions were conducted at the surface of small unilamellar vesicles (SUVs) to provide onto-vesicle chemistry with efficient innovative ready-for-use tools. For that purpose, four amphiphilic molecules were designed to insert into bilayers while presenting a reactive functional head. In this manner, a dioleylglycero-ethoxy-ethoxy-ethoxy-ethanamine (DOG-PEG(4)-NH2) was chosen as a common platform while the reactive amine head was converted into several electrophilic functions. Thus, two dioleylglycerol-based cyclooctyne anchors were prepared: cyclooct-1-yn-3-glycolic acid-based anchor (DOG-COA) and 1-fluorocyclooct-2-ynecarboxylic acid-based anchor (DOG-FCOA). The last one differed from the first one in that a fluorine atom reinforces the electrophilic properties of the unsaturated bond. In addition, a third dioleylglycerol-based triphenylphosphine (DOG-PPh3) was synthesized for the first time. These three innovative amphiphilic anchors were designed to react with any azide-based biomolecule following copper-free Huisgen 1,4-cycloaddition and Staudinger ligation, respectively. A fourth anchor bearing a 3,4-dibromomaleimide ring (DOG-DBM) was also unprecedentedly synthesized, to be further substituted by two thiols. Model reactions conducted in solution with either model biotinyl azide or model biotinyl disulfide gave good to total conversions and excellent isolated yields. The four new anchors were inserted into SUVs whose formula is classically used in in vivo biology. Stability and surface overall electrostatic charge were in the expected range and constant over the study. Then, the functionalized liposomes were ligated to biotin-based reagents and the experimental conditions were finely tuned to optimize the conversion. The biotinyl liposomes were demonstrated functional and totally accessible in an affinity test based on biotin scaffold quantification. Finally, DOG-FCOA's reactivity was confronted to that of DOG-DBM in a 'one-pot' orthogonal reaction. (Biotin-S)(2) and TAMRA-N-3 (tetramethylcarboxyrhodamine azide) were successively conjugated to the liposome suspension in a successful manner. These data implement and reinforce the interest of bioorthogonal click-like reactions onto lipid nanoparticles. (C) 2015 Elsevier Ireland Ltd. All rights reserved.