(4R,8R)-4,8,12-trimethyltridecyl acetate | 94307-25-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (4R,8R)-4,8,12-trimethyltridecyl acetate
• 英文别名: [(4R,8R)-4,8,12-trimethyltridecyl] acetate
• CAS: 94307-25-2
• 化学式: C₁₈H₃₆O₂
• 分子量: 284.483
• InChiKey: AFAFRMPTMLGNKD-IAGOWNOFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  20
• 可旋转键数：
  13
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (4R,8R)-4,8,12-trimethyltridecyl acetate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 2.0h， 以92%的产率得到(4R,8R)-4,8,12-trimethyltridecan-1-ol
  参考文献：
  名称：

  铜催化不对称1,2-加成反应合成（R，R，R）-γ-生育酚

  摘要：

  基于不对称铜催化的格氏试剂与酮的1,2加成反应，经12步（最长的线性序列）合成了（R，R，R）-γ-生育酚，收率为36％。苯并二氢吡喃环的手性中心是通过将植物醇衍生的格利雅试剂1,2-添加到由2,3-二甲基醌制得的α-溴烯酮中而以73％ee构成的。

  DOI：

  10.1002/chem.201404458
• 作为产物：
  描述：

  α-tocopherol quinone 在 臭氧 作用下， 以 二氯甲烷 为溶剂， 生成 (4R,8R)-4,8,12-trimethyltridecyl acetate
  参考文献：
  名称：

  Mayer,H. et al., Helvetica Chimica Acta, 1963, vol. 46, p. 963 - 982

  摘要：

  DOI：

文献信息

• Total Synthesis of (<i>R,R,R</i>)-γ-Tocopherol through Cu-Catalyzed Asymmetric 1,2-Addition
  作者：Zhongtao Wu、Syuzanna R. Harutyunyan、Adriaan J. Minnaard

  DOI：10.1002/chem.201404458

  日期：2014.10.27

  Based on the asymmetric copper‐catalyzed 1,2‐addition of Grignard reagents to ketones, (R,R,R)‐γ‐tocopherol has been synthesized in 36 % yield over 12 steps (longest linear sequence). The chiral center in the chroman ring was constructed with 73 % ee by the 1,2‐addition of a phytol‐derived Grignard reagent to an α‐bromo enone prepared from 2,3‐dimethylquinone.

  基于不对称铜催化的格氏试剂与酮的1,2加成反应，经12步（最长的线性序列）合成了（R，R，R）-γ-生育酚，收率为36％。苯并二氢吡喃环的手性中心是通过将植物醇衍生的格利雅试剂1,2-添加到由2,3-二甲基醌制得的α-溴烯酮中而以73％ee构成的。
• Highly stereoselective construction of the C2 stereocentre of α-tocopherol (vitamin E) by asymmetric addition of Grignard reagents to ketones
  作者：Bartosz Bieszczad、Declan G. Gilheany

  DOI：10.1039/c7ob00751e

  日期：——

  Tertiary alcohol precursors of both C2 diastereoisomers of α-tocopherol were prepared in three ways by our recently reported asymmetric Grignard synthesis. The versatility of Grignard chemistry inherent in its three-way disconnection was exploited to allow the synthesis of three product grades: 77:23 dr (5 steps), 81:19 dr (5 steps) and 96:4 dr (7 steps, one gram scale) from readily available and abundant

  通过我们最近报道的不对称格利雅（Grignard）合成，以三种方式制备了α-生育酚的两个C2非对映异构体的叔醇前体。利用格利雅化学在三向断开中固有的多功能性，可以合成三种产品等级：77 : 23 dr（5步），81 ：19 dr（5步）和96 ：4 dr（7步，一个（克级）的数据来自易于获得的丰富原材料。将产物分三步转化为各自的α-生育酚，从而可以对其绝对构型进行确定的重新分配。
• 一种(2R，4’R，8’R)-α-生育酚的立体选择性全合成方法
  申请人：复旦大学

  公开号：CN114105932A

  公开（公告）日：2022-03-01

  本发明公开了一种(2R，4’R，8’R)‑α‑生育酚的立体选择性全合成方法。本发明包括：以三甲基氢醌为原料碘化生成芳香卤代物，再与含末端烯键的双酯经过Heck反应、Pd/C氢化形成饱和的芳香二酯；再选择性水解双酯生成具有高光学活性的单酯，构建手性立体中心；然后经过甲基磺酰氯化、四氢铝锂还原形成含甲基的手性化合物；再经过氧化关环、氢化还原构建手性色满母核；然后经过苄基保护、Wittig反应、与C15*脂肪类长链膦盐实现碳碳键连接；最后还原双键得到(2R，4’R，8’R)‑α‑生育酚I。本发明方法原料易得，反应条件温和，操作简便，所用的脂肪酶具有良好的稳定性，催化形式绿色环保，具有工业应用价值。
• Tetrahydro-1,8-naphthyridinol Analogues of α-Tocopherol as Antioxidants in Lipid Membranes and Low-Density Lipoproteins
  作者：Tae-gyu Nam、Christopher L. Rector、Hye-young Kim、Andreas F.-P. Sonnen、Roland Meyer、Werner M. Nau、Jeffrey Atkinson、Julia Rintoul、Derek A. Pratt、Ned A. Porter

  DOI：10.1021/ja072371m

  日期：2007.8.1

  Recently we demonstrated that the C(7)-unsubstituted tetrahydro-1,8-naphthyridin-3-ol has more than an order of magnitude better peroxyl radical trapping activity than alpha-tocopherol (alpha-TOH) in inhibited autoxidations in benzene. In order to prepare analogues more structurally related to alpha-TOH for further studies in vitro and in vivo, we developed synthetic approaches to C(7)-monoalkyl and C(7)-dialkyl analogues using a sequence involving (1) AgNO3-mediated hydroxymethyl radical addition to 1,8-naphthyridine, (2) regioselective alkyllithium addition by cyclic chelation in a nonpolar solvent, (3) iodination of the naphthyridine at C(3), and (4) CuI-medidated benzyloxylation of the aryl iodide followed by catalytic hydrogenolysis. An alpha-TOH isostere was prepared by a Wittig coupling of a C-16 side chain identical to that of alpha-TOH to the naphthyridinols. The C(7)-mono- and dialkyl analogues exhibited more than an order of magnitude higher antioxidant activity (k(inh) = (5.3-6.1) x 10(7) M-1 s(-1)) than alpha-TOH (k(inh) = 0.35 x 10(7) M-1 s(-1)) in benzene, as determined by a newly developed peroxyl radical clock. In addition to the strong antioxidant activity in benzene, the closest alpha-TOH analogue (naphthyridinol-based tocopherol, N-TOH) showed excellent inhibition of the oxidation of cholesteryl esters in human low-density lipoprotein and spared endogenous alpha-TOH in these experiments. Lateral diffusion of N-TOH in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine liposomes was comparable to that of alpha-TOH, suggesting that it will have good antioxidant characteristics in both membranes and lipoproteins. Furthermore, a binding assay using a fluorescent tocopherol analogue showed that N-TOH binds to recombinant human tocopherol transfer protein better than alpha-TOH itself, suggesting that distribution of unnatural antioxidants such as N-TOH in vivo is possible.
• Design, Synthesis, and Estrogenic Activity of a Novel Estrogen Receptor ModulatorA Hybrid Structure of 17β-Estradiol and Vitamin E in Hippocampal Neurons
  作者：Liqin Zhao、Chunyang Jin、Zisu Mao、Madathil B. Gopinathan、Kenneth Rehder、Roberta D. Brinton

  DOI：10.1021/jm070546x

  日期：2007.9.1

  We recently discovered that ICI 182,780 (1), an antagonist of estrogen receptor (ER)-dependent proliferation in reproductive tissues, functions as an estrogenic agonist in primary neurons. The present study investigated whether the agonist properties of 1 in neurons could be translated into structural analogs. 7 alpha[(4R,8R)-4,8,-12-trimethyltridecyl]estra-1,3,5-trien-3,17 beta-diol (2), a hybrid structure of 17 beta-estradiol and vitamin E, was synthesized and found to bind to both ER alpha and ER beta. In vitro analyses demonstrated that 2 was neuroprotective and effective in activating molecular mechanisms associated with estrogenic agonist activity in rat primary hippocampal neurons. Collectively, the data support an estrogenic agonist profile of 2 action comparable to 1 in primary neurons, confirming that estrogenic activity of I in neurons is not a unique phenomenon. These results provide support for the development of a brain-selective ER modulator, with potential as an efficacious and safe estrogen alternative to prevent Alzheimer's disease and cognitive decline in postmenopausal women.