9-((2R)-6-{[tert-butyl(dimethyl)-silyl]-oxy}-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromene-2-yl)-1-nonanol | 220954-00-7

• 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: 9-((2R)-6-{[tert-butyl(dimethyl)-silyl]-oxy}-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromene-2-yl)-1-nonanol
• 英文别名: (R)-9-(6-(tert-butyldimethylsilanyloxy)-2,5,7,8-tetramethylchroman-2-yl)nonan-1-ol；(R)-(9-(6-tert-butyl-dimethyl-silanyloxy)-2,5,7,8-tetramethylchroman-2-yl)nonanol；9-[(2R)-6-[tert-butyl(dimethyl)silyl]oxy-2,5,7,8-tetramethyl-3,4-dihydrochromen-2-yl]nonan-1-ol
• CAS: 220954-00-7
• 化学式: C₂₈H₅₀O₃Si
• 分子量: 462.789
• InChiKey: FCXUXPODLAPUNC-MUUNZHRXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.19
• 重原子数：
  32
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.79
• 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：

  9-((2R)-6-{[tert-butyl(dimethyl)-silyl]-oxy}-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromene-2-yl)-1-nonanol 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 3.08h， 生成 5-dimethylamino-naphthalene-1-sulfonic acid {9-[(R)-6-(tert-butyl-dimethyl-silanyloxy)-2,5,7,8-tetramethyl-chroman-2-yl]nonyl}-amide
  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 9-((2R)-6-{[tert-butyl(dimethyl)-silyl]-oxy}-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromene-2-yl)-1-nonanol
  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 and properties of double-stranded RNA-bindable oligodiaminogalactose derivatives conjugated with vitamin E
  作者：Rintaro Iwata、Kazutaka Nishina、Takanori Yokota、Takeshi Wada

  DOI：10.1016/j.bmc.2013.12.060

  日期：2014.2

  duplex-bindable molecule with an oligodiaminosaccharide structure. These 2,6-diamino-2,6-dideoxy-(1-4)-β-d-galactopyranose oligomers (oligodiaminogalactoses; ODAGals) conjugated with α-tocopherol (vitamin E; VE) or a VE analog were designed as novel siRNA-bindable molecules that can be utilized to deliver RNAi drugs to the liver. Among these compounds, the VE analog-bound ODAGal was suggested to bind

  RNA干扰（RNAi）是一种基因调控系统，由外部短干扰RNA（siRNA）控制。siRNA的序列选择性基因沉默在临床研究中显示出希望。但是，几乎没有有效的方法可将siRNA传递至靶细胞。在这项研究中，我们提出了一种新型的具有寡二氨基糖结构的RNA双链可结合分子。将这些与α-生育酚（维生素E； VE）或VE类似物缀合的2，6-二氨基-2，6-二脱氧-（1-4）-β- d-吡喃半乳糖低聚物（oligodiaminogalactoses； ODAGals）设计为新型siRNA可用于将RNAi药物递送至肝脏的可结合分子。在这些化合物中，VE-结合的ODAGal被建议与RNA双链体结合而不抑制RNAi活性。
• Tocopherol derivatives and uses thereof
  申请人：Atkinson Jeffrey

  公开号：US20080293792A1

  公开（公告）日：2008-11-27

  Tocopherol derivatives having the general formula: wherein n is an integer of 6 to 13, R 1 is hydrogen, a silyl ether or acetate, R 2 is an optionally substituted nitrogen-containing heterocycle or a polycyclic nitrogen-containing heterocycle; and pharmaceutically acceptable salts thereof are provided. A method for synthesizing the compounds is also provided. The tocopherol derivatives are capable of inhibiting the primary enzyme responsible for the metabolism of the tocopherols and tocotrienols compounds of vitamin E, namely tocopherol-ω-hydroxylase, and thus increase the amount and prolong the availability of these compounds in plasma and tissue.

  提供具有一般公式的生育酚衍生物：其中n是6到13的整数，R1是氢，硅醚或醋酸酯，R2是一个可选择地取代的含氮杂环或多环含氮杂环；以及其药用可接受的盐。还提供了一种合成这些化合物的方法。这些生育酚衍生物能够抑制生育酚和生育三烯酚（维生素E化合物）的代谢的主要酶，即生育酚-ω-羟基化酶，从而增加这些化合物在血浆和组织中的含量并延长其可用性。
• 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 and properties of vitamin E analog-conjugated neomycin for delivery of RNAi drugs to liver cells
  作者：Rintaro Iwata、Futoshi Nakayama、Sakie Hirochi、Kazuki Sato、Wenying Piao、Kazutaka Nishina、Takanori Yokota、Takeshi Wada

  DOI：10.1016/j.bmcl.2014.12.079

  日期：2015.2

  is a promising tool to regulate gene expression by external double stranded RNAs (dsRNAs) such as siRNAs. As an efficient method to deliver siRNAs to liver cells, we propose a novel strategy using vitamin E (VE)-conjugated neomycin derivatives. With the aim of delivering RNAi-based drugs to liver cells, several tripod-type and prodrug-type neomycin derivatives were synthesized, all of which were thermodynamically

  RNA干扰（RNAi）是一种有前途的工具，可通过诸如siRNA的外部双链RNA（dsRNA）调节基因表达。作为将siRNA传递至肝细胞的有效方法，我们提出了一种使用维生素E（VE）结合的新霉素衍生物的新策略。为了将基于RNAi的药物递送至肝细胞，合成了几种三脚型和前药型新霉素衍生物，所有这些衍生物都是热力学稳定的RNA双链体。前药型衍生物7和三脚架型衍生物10被递送至肝癌细胞并成功诱导RNAi活性。这些结果表明天然氨基糖苷作为RNAi药物载体的潜在用途。
• Inhibition of oxidative metabolism of tocopherols with ω-N-heterocyclic derivatives of vitamin E
  作者：Stephan Ohnmacht、Phillip Nava、Ryan West、Robert Parker、Jeffrey Atkinson

  DOI：10.1016/j.bmc.2008.07.020

  日期：2008.8

  The oxidative metabolism of tocopherols and tocotrienols by monooxygenases is a key factor in the plasma and tissue clearance of forms of vitamin E other than alpha-tocopherol. It is well known that a commonly ingested form of vitamin E, gamma-tocopherol, has greatly reduced plasma half-life (faster clearance) than alpha-tocopherol. The tocotrienols are metabolized even faster than gamma-tocopherol. Both gamma-tocopherol and alpha- and delta-tocotrienol possess intriguing biological activities that are different from alpha-tocopherol, making them potentially of interest for therapeutic use. Unfortunately, the fast clearance of non-alpha-tocopherols from animal tissues is a significant hurdle to maximizing their effect(s) as dietary supplements. We report here the design and synthesis of N-heterocycle-containing analogues of alpha-tocopherol that act as inhibitors of Cyp4F2, the key monooxygenase responsible for omega-hydroxylation of the side chain of tocols. In particular, an omega-imidazole containing compound, 1, [(R)-2-(9-(1H-imidazol-1-yl)nonyl)-2,5,7,8-tetramethylchroman-6-ol] had an ED50 for inhibition of gamma-CEHC production from c-tocopherol of similar to 1 nM when tested in HepG2 cells in culture. Furthermore, feeding of 1 to mice along with rapidly metabolized delta-tocopherol, resulted in a doubling of the delta-tocopherol/alpha-tocopherol ratio in liver ( P<0.05). Thus, 1 may be a useful adjuvant to the therapeutic use of non-alpha-tocopherols. (C) 2008 Elsevier Ltd. All rights reserved.