tert-butyl-3β-cholest-5-en-3-yl[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]carbamate | 1039089-35-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: tert-butyl-3β-cholest-5-en-3-yl[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]carbamate
• 英文别名: tert-Butyl-3beta-cholest-5-en-3-yl[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]carbamate；tert-butyl N-[(3S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl]-N-[3-(1,3-dioxoisoindol-2-yl)propyl]carbamate
• CAS: 1039089-35-4
• 化学式: C₄₃H₆₄N₂O₄
• 分子量: 672.992
• InChiKey: OYOGBMSLFUBROL-OIBVWVTKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.1
• 重原子数：
  49
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  66.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl-3β-cholest-5-en-3-yl[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]carbamate 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 肼 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 16.5h， 生成 (9H-fluoren-9-yl)methyl {3-[(3-{(tert-butoxycarbonyl)[3β-cholest-5-en-3-yl]amino}propyl)amino]-3-oxopropyl}carbamate
  参考文献：
  名称：

  Fluorescent mimics of cholesterol that rapidly bind surfaces of living mammalian cells

  摘要：

  新型类固醇类似物通过受体介导的途径迅速大量地被纳入活体哺乳动物细胞的质膜中。

  DOI：

  10.1039/c5cc06325f
• 作为产物：
  描述：

  2-[3-[[(3S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl]amino]propyl]isoindole-1,3-dione 、 二碳酸二叔丁酯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以465 mg的产率得到tert-butyl-3β-cholest-5-en-3-yl[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]carbamate
  参考文献：
  名称：

  Selective Disruption of Early/Recycling Endosomes: Release of Disulfide-Linked Cargo Mediated by a N-Alkyl-3β-Cholesterylamine-Capped Peptide

  摘要：

  The use of endocytic uptake pathways to deliver poorly permeable molecules into mammalian cells is often plagued by entrapment and degradation of material in late endosomes and lysosomes. As a strategy to prevent the exposure of cargo to these highly hydrolytic membrane-sealed compartments, we synthesized derivatives of the membrane anchor N-alkyl-3 beta-cholesterylamine that selectively target linked compounds to less hydrolytic early/recycling endosomes. By targeting a pH-dependent membrane-lytic dodecapeptide and dislufide-linked flurophore to these compartments in Chinese hamster ovary cells or Jurkat lymphocytes, membranes of early-recycling endosomes were selectively disrupted, resulting in cleavage of the disulphide and escape of the fluorophore into cytosol and nucleus with low toxicity. The ability os appropriately designed N-alkyl-3 beta-cholesterylamines to deliver cargo into and release dislufide-linked cargo from relatively nonhydrolytic early/recycling endosomes may be useful for the delivery of a variety of sensitive molecules into living mammalian cells.

  DOI：

  10.1021/ja803380a

文献信息

• Synthetic mimics of mammalian cell surface receptors: method and compositions
  申请人：Peterson R. Blake

  公开号：US20060229235A1

  公开（公告）日：2006-10-12

  The present invention relates to new synthetic receptors. More particularly, the present invention relates to the use of the synthetic receptors for delivering a protein, peptide, drug, prodrug, lipid, nucleic acid, carbohydrate or small molecule into a target cell via receptor-mediated endocytosis. According to the invention, novel synthetic mimics of cell surface receptors have been designed and methods for use of the same are disclosed.

  本发明涉及新的合成受体。更具体地，本发明涉及利用合成受体通过受体介导的内吞作用将蛋白质、肽、药物、前药、脂质、核酸、碳水化合物或小分子输送到靶细胞中。根据本发明，已设计了细胞表面受体的新型合成模拟物，并公开了其使用方法。
• DISRUPTORS OF EARLY/RECYCLING ENDOSOMES
  申请人：Peterson Blake R.

  公开号：US20100041773A1

  公开（公告）日：2010-02-18

  A delivery system for introducing a cargo molecule into cytosol of a living cell can include: a first membrane binding element linked to an endosomal compartment disrupting element through a first linker having one or more anionic moieties; and a second membrane binding element linked to an exogenous cargo molecule through a second linker having one or more anionic moieties, the second linker having a region that is selectively cleavable, wherein the first and second membrane binding elements both induce endocytosis into an early/recycling endosome and the endosomal compartment disrupting element destabilizes the early/recycling endosome such that the exogenous cargo molecule is released from the second membrane binding element and into the cytosol of the living cell.

  一种将货物分子引入活细胞细胞质的传递系统可以包括：第一膜结合元素通过第一连接物与内体室破坏元素相连，第一连接物具有一个或多个阴离子基团；第二膜结合元素通过第二连接物与外源性货物分子相连，第二连接物具有一个或多个阴离子基团，并具有一个可选择性断裂的区域。其中，第一和第二膜结合元素均引起内吞作用进入早期/回收内体，并且内体室破坏元素破坏早期/回收内体，使外源性货物分子从第二膜结合元素中释放并进入活细胞细胞质。
• SYNTHETIC MIMICS OF MAMMALIAN CELL SURFACE RECEPTORS: METHOD AND COMPOSITIONS
  申请人：PETERSON BLAKE R.

  公开号：US20100160657A1

  公开（公告）日：2010-06-24

  The present invention relates to new synthetic receptors. More particularly, the present invention relates to methods for synthesizing preferred membrane-binding elements, preferably cholesterylamine derivatives, including 3β-amino-5-cholestene (3β-cholesterylamine) and related 3β-halides through i-steroid and retro-i-steroid rearrangements. The invention further relates to use of the synthetic receptors for delivering a protein, peptide, drug, prodrug, lipid, nucleic acid, carbohydrate or small molecule into a target cell via receptor-mediated endocytosis. According to the invention, novel synthetic mimics of cell surface receptors have been designed and methods for use of the same are disclosed.

  本发明涉及新的合成受体。更具体地说，本发明涉及用于合成首选膜结合元素（优选为胆固醇胺衍生物，包括3β-氨基-5-胆甾烷（3β-胆固醇胺）和相关的3β-卤化物）的方法，包括通过i-类固醇和retro-i-类固醇重排。本发明进一步涉及利用合成受体通过受体介导的内吞作用将蛋白质、肽、药物、前药、脂质、核酸、碳水化合物或小分子输送到靶细胞的用途。根据本发明，新的细胞表面受体合成类似物已被设计，并公开了使用这些类似物的方法。
• Disruptors of early/recycling endosomes
  申请人：Peterson Blake R.

  公开号：US08889631B2

  公开（公告）日：2014-11-18

  A delivery system for introducing a cargo molecule into cytosol of a living cell can include: a first membrane binding element linked to an endosomal compartment disrupting element through a first linker having one or more anionic moieties; and a second membrane binding element linked to an exogenous cargo molecule through a second linker having one or more anionic moieties, the second linker having a region that is selectively cleavable, wherein the first and second membrane binding elements both induce endocytosis into an early/recycling endosome and the endosomal compartment disrupting element destabilizes the early/recycling endosome such that the exogenous cargo molecule is released from the second membrane binding element and into the cytosol of the living cell.

  将货物分子引入活细胞细胞质的传递系统可以包括：第一膜结合元素通过具有一个或多个阴离子基团的第一连接子与内体室破坏元素相连；以及第二膜结合元素通过具有一个或多个阴离子基团的第二连接子与外源性货物分子相连，第二连接子具有可选择性断裂的区域，其中第一和第二膜结合元素都诱导内吞作用进入早期/循环内体质，并且内体室破坏元素破坏早期/循环内体质，使得外源性货物分子从第二膜结合元素中释放出来并进入活细胞细胞质。
• [EN] SYNTHETIC CHOLESTERYLAMINE-LINKER DERIVATIVES FOR AGENT DELIVERY INTO CELLS<br/>[FR] DÉRIVÉS SYNTHÉTIQUES DE CHOLESTÉRYLAMINE-LIEUR POUR L'ADMINISTRATION INTRACELLULAIRE D'AGENTS
  申请人：UNIV KANSAS

  公开号：WO2011019942A3

  公开（公告）日：2011-07-14