8-((2R)-6-{[tert-butyl(dimethyl)-silyl]-oxy}-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromene-2-yl)-1-octanol | 220953-99-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 8-((2R)-6-{[tert-butyl(dimethyl)-silyl]-oxy}-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromene-2-yl)-1-octanol
• 英文别名: 8-[(2R)-6-[tert-butyl(dimethyl)silyl]oxy-2,5,7,8-tetramethyl-3,4-dihydrochromen-2-yl]octan-1-ol
• CAS: 220953-99-1
• 化学式: C₂₇H₄₈O₃Si
• 分子量: 448.762
• InChiKey: ZPXDPLYPVIVLIX-HHHXNRCGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.8
• 重原子数：
  31
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.78
• 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：

  8-((2R)-6-{[tert-butyl(dimethyl)-silyl]-oxy}-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromene-2-yl)-1-octanol 在 4-二甲氨基吡啶 、 lithium aluminium tetrahydride 、 sodium azide 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 8-((2R)-6-{[tert-butyl(dimethyl)silyl]oxy}-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl)-octylamine
  参考文献：
  名称：

  Preparation of fluorescent tocopherols for use in protein binding and localization with the α-tocopherol transfer protein

  摘要：

  Sixteen fluorescent analogues of the lipid-soluble antioxidant vitamin alpha-tocopherol were prepared incorporating fluorophores at the terminus of omega-functionalized 2-n-alkyl-substituted chromanols (1a-d and 4a-d) that match the methylation pattern of alpha-tocopherol, the most biologically active form of vitamin E. The fluorophores used include 9-anthroyloxy (AO), 7-nitrobenz-2-oxa-1,3-diazole (NBD), N-methyl anthranilamide (NMA), and dansyl (DAN). The compounds were designed to function as fluorescent reporter ligands for protein-binding and lipid transfer assays. The fluorophores were chosen to maximize the fluorescence changes observed upon moving from an aqueous environment (low fluorescence intensity) to an hydrophobic environment such as a protein's binding site (high fluorescence intensity). Compounds 9d (anthroyloxy) and 10d (nitrobenzoxadiazole), having a C9-carbon chain between the chromanol and the fluorophore, were shown to bind specifically and reversibly to recombinant human tocopherol transfer protein (alpha-TTP) with dissociation constants of approximately 280 and 60 nM, respectively, as compared to 25 nM for the natural ligand 2R,4'R,8'R-alpha-tocopherol. Thus, compounds have been prepared that allow the investigation of the rate of alpha-TTP-mediated inter-membrane transfer of alpha-tocopherol and to investigate the mechanism of alpha-TTP function at membranes of different composition. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.01.053
• 作为产物：
  描述：

  (S)-(-)-methyl 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylate 在 palladium on activated charcoal 咪唑 、 氢气 、 二异丁基氢化铝 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 正己烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 29.5h， 生成 8-((2R)-6-{[tert-butyl(dimethyl)-silyl]-oxy}-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromene-2-yl)-1-octanol
  参考文献：
  名称：

  基于α-生育酚的肌醇六磷酸和苯并二氢吡喃衍生的光亲和标记的合成。

  摘要：

  α-生育酚的光亲和性类似物已经通过在模仿生育酚尾部的植酸尾部的变长的烷基链的末端或在生育酚的苯并二氢吡喃的C-3上取代光敏官能团而制备。烷基链改性的化合物2a-d包含从苯并二氢吡喃的C-2延伸的己基至壬基烷基链，其终止于四氟叠氮基苄氧基。这些化合物从市售的Trolox酸4开始制备，然后进行酯化，保护和还原为甲硅烷基保护的Trolox醛7，使用Wittig化学方法将其偶联到不同的ω-羟基bro溴化物上。烯烃产物的还原，与对叠氮基四氟苄基溴的偶合以及酚硅烷基的脱保护，以优异的收率得到化合物2a-d。色度官能化的光亲和标记是从受保护的生育酚苯烯16b合成的，后者是制备3-羟基衍生物的关键中间体，方法是还原由Jacobsen催化剂直接产生的环氧化物，或通过在湿DME中用NBS处理得到两种立体异构体将其溴环化并还原得到苯酚保护的C-3醇19a，b。然后将这些醇转化为重氮乙酸酯，并除去保护基，得到3-

  DOI：

  10.1021/jo000029l

文献信息

• Synthesis of photoaffinity label analogues of α-tocopherol
  作者：Huangshu Lei、Virginia Marks、Tony Pasquale、Jeffrey K. Atkinson

  DOI：10.1016/s0960-894x(98)00655-6

  日期：1998.12

  Photoaffinity analogues of alpha-tocopherol have been synthesized that incorporate the photosensitive 4-azido-2,3,5,6-tetrafluorobenzyloxy group at the terminus of unbranched analogues of the naturally occurring phytyl side chain. An intermediate from these syntheses has also been used to generate a supported ligand for bioaffinity chromatography of alpha-tocopherol binding proteins.

  已经合成了α-生育酚的光亲和性类似物，其在天然存在的植酸基侧链的直链类似物的末端结合了光敏的4-叠氮基-2,3,5,6-四氟苄氧基。这些合成的中间体也已用于产生支持的配体，用于α-生育酚结合蛋白的生物亲和层析。
• Synthesis of Phytyl- and Chroman-Derivatized Photoaffinity Labels Based on α-Tocopherol
  作者：Huangshu Lei、Jeffrey Atkinson

  DOI：10.1021/jo000029l

  日期：2000.4.1

  prepared by substituting photosensitive functional groups at either the terminus of an alkyl chain of varying length mimicking the phytyl tail or on C-3 of the chroman portion of tocopherol. The alkyl chain-modified compounds 2a-d contain a hexyl to nonyl alkyl chain extending from C-2 of the chroman, terminating in a tetrafluoroazidobenzyloxy group. These compounds were prepared starting from the commercially

  α-生育酚的光亲和性类似物已经通过在模仿生育酚尾部的植酸尾部的变长的烷基链的末端或在生育酚的苯并二氢吡喃的C-3上取代光敏官能团而制备。烷基链改性的化合物2a-d包含从苯并二氢吡喃的C-2延伸的己基至壬基烷基链，其终止于四氟叠氮基苄氧基。这些化合物从市售的Trolox酸4开始制备，然后进行酯化，保护和还原为甲硅烷基保护的Trolox醛7，使用Wittig化学方法将其偶联到不同的ω-羟基bro溴化物上。烯烃产物的还原，与对叠氮基四氟苄基溴的偶合以及酚硅烷基的脱保护，以优异的收率得到化合物2a-d。色度官能化的光亲和标记是从受保护的生育酚苯烯16b合成的，后者是制备3-羟基衍生物的关键中间体，方法是还原由Jacobsen催化剂直接产生的环氧化物，或通过在湿DME中用NBS处理得到两种立体异构体将其溴环化并还原得到苯酚保护的C-3醇19a，b。然后将这些醇转化为重氮乙酸酯，并除去保护基，得到3-
• Preparation of fluorescent tocopherols for use in protein binding and localization with the α-tocopherol transfer protein
  作者：Phillip Nava、Matt Cecchini、Sara Chirico、Heather Gordon、Samantha Morley、Danny Manor、Jeffrey Atkinson

  DOI：10.1016/j.bmc.2006.01.053

  日期：2006.6

  Sixteen fluorescent analogues of the lipid-soluble antioxidant vitamin alpha-tocopherol were prepared incorporating fluorophores at the terminus of omega-functionalized 2-n-alkyl-substituted chromanols (1a-d and 4a-d) that match the methylation pattern of alpha-tocopherol, the most biologically active form of vitamin E. The fluorophores used include 9-anthroyloxy (AO), 7-nitrobenz-2-oxa-1,3-diazole (NBD), N-methyl anthranilamide (NMA), and dansyl (DAN). The compounds were designed to function as fluorescent reporter ligands for protein-binding and lipid transfer assays. The fluorophores were chosen to maximize the fluorescence changes observed upon moving from an aqueous environment (low fluorescence intensity) to an hydrophobic environment such as a protein's binding site (high fluorescence intensity). Compounds 9d (anthroyloxy) and 10d (nitrobenzoxadiazole), having a C9-carbon chain between the chromanol and the fluorophore, were shown to bind specifically and reversibly to recombinant human tocopherol transfer protein (alpha-TTP) with dissociation constants of approximately 280 and 60 nM, respectively, as compared to 25 nM for the natural ligand 2R,4'R,8'R-alpha-tocopherol. Thus, compounds have been prepared that allow the investigation of the rate of alpha-TTP-mediated inter-membrane transfer of alpha-tocopherol and to investigate the mechanism of alpha-TTP function at membranes of different composition. (c) 2006 Elsevier Ltd. All rights reserved.