2-[18F]fluoro-2,2-difluoroethyl tosylate | 1300731-45-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-[18F]fluoro-2,2-difluoroethyl tosylate
• 英文别名: [¹⁸F]2,2,2-trifluoroethyl tosylate；(2-(18F)fluoranyl-2,2-difluoroethyl) 4-methylbenzenesulfonate
• CAS: 1300731-45-6
• 化学式: C₉H₉F₃O₃S
• 分子量: 253.231
• InChiKey: IGKCQDUYZULGBM-LMANFOLPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  51.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-[18F]fluoro-2,2-difluoroethyl tosylate 、 3-氯-1,2-丙二醇 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Radiosynthesis of the tumor hypoxia marker [18F]TFMISO via O-[18F]trifluoroethylation reveals a striking difference between trifluoroethyl tosylate and iodide in regiochemical reactivity toward oxygen nucleophiles

  摘要：

  The MRI hypoxia marker trifluoromisonidazole (TFMISO) [1-(2-nitro-1H-imidazol-1-yl)-3-(2,2,2-trifluoroethoxy) propan-2-ol] was successfully labeled with F-18 to expand its role into a bimodal PET/MRI probe. F-18-Labeling was achieved via a three-step procedure in which 2,2,2-[F-18]trifluoroethyl p-toluenesulfonate prepared by F-18-F-19 exchange served as the [F-18]trifluoroethylating agent. The O-[F-18]trifluoroethylation reaction proceeded efficiently to give the intermediate 1,2-epoxy-3-(2,2,2-[F-18]trifluoroethoxy) propane, with approximately 60% of F-18 incorporated from the tosylate precursor, which was condensed with 2-nitroimidazole to yield [F-18] TFMISO. Approximately 40% of the [F-18] trifluoroethyl tosylate precursor was converted into the final product. In stark contrast, 2,2,2-[F-18] trifluoroethyl iodide failed to produce [F-18] TFMISO, giving instead 1,1-[F-18]difluoro-2-iodoethoxy and 1-[F-18]fluoro-2-iodovinyloxy analogs of [F-18] TFMISO. Thus, this investigation has identified 2,2,2-[F-18] trifluoroethyl tosylate as an excellent [F-18] trifluoroethylating agent, which can convert efficiently an alcohol into the corresponding [F-18] trifluoroethyl ether. (C) 2011 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2011.02.026
• 作为产物：
  描述：

  2,2-difluorovinyl tosylate 在 C₁₈H₃₆N₂O₆*K⁽¹⁺⁾*⁽¹⁸⁾FK 作用下， 以 二甲基亚砜 、 水 为溶剂， 生成 2-[18F]fluoro-2,2-difluoroethyl tosylate
  参考文献：
  名称：

  A simple, rapid procedure for nucleophilic radiosynthesis of aliphatic [18F]trifluoromethyl groups

  摘要：

  已经开发了一种通过将1,1-二氟乙烯前体与[18F]氟离子反应，合成脂肪族[18F]三氟甲基团的放射合成程序，结果等同于H[18F]F的直接亲核加成。随后获得了多种18F标记的模型化合物，并通过从1,1-二氟乙烯-2-基4-甲苯磺酸酯出发的两步过程合成了两种潜在的[18F]放射示踪剂。该方法广泛适用于合成新颖的放射示踪剂，具有高放射化学产率和良好的特异性活性。

  DOI：

  10.1039/c1cc15342k

文献信息

• Synthesis of [¹⁸F]PS13 and Evaluation as a PET Radioligand for Cyclooxygenase-1 in Monkey
  作者：Carlotta Taddei、Cheryl L. Morse、Min-Jeong Kim、Jeih-San Liow、Jose Montero Santamaria、Andrea Zhang、Lester S. Manly、Paolo Zanotti-Fregonara、Robert L. Gladding、Sami S. Zoghbi、Robert B. Innis、Victor W. Pike

  DOI：10.1021/acschemneuro.0c00737

  日期：2021.2.3

  cyclotron-produced [18F]fluoride ion to gem-difluorovinyl precursors, either to label PS13 in one step or to produce [18F]2,2,2-trifluoroethyl p-toluenesulfonate for labeling a hydroxyl precursor. From the latter two-step approach, we obtained [18F]PS13 ready for intravenous injection in a decay-corrected radiochemical yield of 7.9% and with a molar activity of up to 7.9 GBq/μmol. PET imaging of monkey

  环氧合酶-1 (COX-1) 及其同工酶 COX-2 是合成前列腺素的关键酶。使用正电子发射断层扫描 (PET) 对 COX-1 和 COX-2 选择性放射性配体进行成像可以阐明这些酶如何参与炎症状况并有助于发现改进的抗炎药物。我们之前已经标记了选择性高亲和力 COX-1 配体 1,5-bis(4-methoxyphenyl)-3-(2,2,2-trifluoroethoxy)-1 H -1,2,4-triazole (PS13) , 含碳 11 ( t 1/2 = 20.4 分钟)。这种放射性配体 ([ 11 C]PS13) 已成功用于猴子和人脑以及外围的 COX-1 的 PET 成像。[ 11 C]PS13 正在临床研究中使用。用氟 18 替代 PS13 标记（t 1/2 = 109.8 分钟）是理想的，以提供一种寿命更长的高活性放射性配体，可以很容易地分布在成像中心之间。然而，在其 1
• Radiosynthesis and characterization of astemizole derivatives as lead compounds toward PET imaging of τ-pathology
  作者：Patrick J. Riss、Laurent Brichard、Valentina Ferrari、David J. Williamson、Tim D. Fryer、Young T. Hong、Jean-Claude Baron、Franklin I. Aigbirhio

  DOI：10.1039/c3md00017f

  日期：——

  Formation of neurofibrillary tangles, comprising of microtubule-associated tau protein, is a hallmark of a group of neurodegenerative diseases, including Alzheimer's disease. In consequence, in vivo imaging of neurofibrillary tangles is a current focus of positron emission tomography research. Herein, development of an in vitro radioligand binding assay which uses synthetic aggregates as a model of neurofibrillary tangles is reported, together with evaluation of novel derivatives of the tau protein ligand astemizole.

  由微管相关 tau 蛋白组成的神经纤维缠结是包括阿尔茨海默病在内的一系列神经退行性疾病的标志。因此，神经纤维缠结的体内成像是目前正电子发射断层扫描研究的重点。本文报告了利用合成聚集体作为神经纤维缠结模型的体外放射性配体结合试验的开发情况，以及对 tau 蛋白配体 astemizole 新型衍生物的评估。
• Direct, nucleophilic radiosynthesis of [18F]trifluoroalkyl tosylates: improved labelling procedures
  作者：Patrick J. Riss、Valentina Ferrari、Laurent Brichard、Paul Burke、Robert Smith、Franklin I. Aigbirhio

  DOI：10.1039/c2ob25802a

  日期：——

  A rapid and efficient protocol to afford the title compound 2-[18F]-fluoro-2,2-difluoroethyl tosylate ([18F]7b) is described. Starting from [18F]fluoride ion, labelling reagent 7b was obtained in good yields and a high specific radioactivity. Compound ([18F]7b) was then used to synthesise a prospective radiotracer for PET-imaging in dementia.

  描述了提供标题化合物 2-[ 18 F]-氟-2,2-二氟乙基甲苯磺酸酯 ([ 18 F] 7b )的快速有效方案。从[ 18 F]氟离子开始，以良好的产率和高比放射性获得标记试剂7b。然后使用化合物([ 18 F] 7b )合成用于痴呆症PET成像的前瞻性放射性示踪剂。
• A simple, rapid procedure for nucleophilic radiosynthesis of aliphatic [18F]trifluoromethyl groups
  作者：Patrick J. Riss、Franklin I. Aigbirhio

  DOI：10.1039/c1cc15342k

  日期：——

  A procedure for the radiosynthesis of aliphatic [18F]trifluoromethyl groups by reacting 1,1-difluorovinyl precursors with [18F]fluoride ions, resulting in the equivalent of direct nucleophilic addition of H[18F]F, has been developed. A variety of 18F-labelled model compounds were then obtained and two potential [18F]radiotracers were synthesised by a two step process starting from 1,1-difluorovin-2-yl 4-toluenesulfonate. The method is widely applicable for the synthesis of novel radiotracers in high radiochemical yields and good specific activity.

  已经开发了一种通过将1,1-二氟乙烯前体与[18F]氟离子反应，合成脂肪族[18F]三氟甲基团的放射合成程序，结果等同于H[18F]F的直接亲核加成。随后获得了多种18F标记的模型化合物，并通过从1,1-二氟乙烯-2-基4-甲苯磺酸酯出发的两步过程合成了两种潜在的[18F]放射示踪剂。该方法广泛适用于合成新颖的放射示踪剂，具有高放射化学产率和良好的特异性活性。
• Radiosynthesis of the tumor hypoxia marker [18F]TFMISO via O-[18F]trifluoroethylation reveals a striking difference between trifluoroethyl tosylate and iodide in regiochemical reactivity toward oxygen nucleophiles
  作者：Makiko Suehiro、Guangbin Yang、Geralda Torchon、Ellen Ackerstaff、John Humm、Jason Koutcher、Ouathek Ouerfelli

  DOI：10.1016/j.bmc.2011.02.026

  日期：2011.4

  The MRI hypoxia marker trifluoromisonidazole (TFMISO) [1-(2-nitro-1H-imidazol-1-yl)-3-(2,2,2-trifluoroethoxy) propan-2-ol] was successfully labeled with F-18 to expand its role into a bimodal PET/MRI probe. F-18-Labeling was achieved via a three-step procedure in which 2,2,2-[F-18]trifluoroethyl p-toluenesulfonate prepared by F-18-F-19 exchange served as the [F-18]trifluoroethylating agent. The O-[F-18]trifluoroethylation reaction proceeded efficiently to give the intermediate 1,2-epoxy-3-(2,2,2-[F-18]trifluoroethoxy) propane, with approximately 60% of F-18 incorporated from the tosylate precursor, which was condensed with 2-nitroimidazole to yield [F-18] TFMISO. Approximately 40% of the [F-18] trifluoroethyl tosylate precursor was converted into the final product. In stark contrast, 2,2,2-[F-18] trifluoroethyl iodide failed to produce [F-18] TFMISO, giving instead 1,1-[F-18]difluoro-2-iodoethoxy and 1-[F-18]fluoro-2-iodovinyloxy analogs of [F-18] TFMISO. Thus, this investigation has identified 2,2,2-[F-18] trifluoroethyl tosylate as an excellent [F-18] trifluoroethylating agent, which can convert efficiently an alcohol into the corresponding [F-18] trifluoroethyl ether. (C) 2011 Published by Elsevier Ltd.