1-(2′-deoxy-2′-[¹⁸F]fluoroarabinofuranosyl)cytosine | 1052670-04-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 1-(2′-deoxy-2′-[¹⁸F]fluoroarabinofuranosyl)cytosine
• 英文别名: 1-(2’-deoxy-2’-[¹⁸F]fluoro-β-D-arabinofuranosyl)cytosine；D-2′-deoxy-2′-[¹⁸F]fluoro-β-D-arabinofuranosylcytosine；D-[¹⁸F]FAC；2'-Fluoro-2'-deoxy-arabinofuranosyl-cytidine F-18；4-amino-1-[(2R,3S,4R,5R)-3-(18F)fluoranyl-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one
• CAS: 1052670-04-8
• 化学式: C₉H₁₂FN₃O₄
• 分子量: 244.212
• InChiKey: NVZFZMCNALTPBY-OEXKADLXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-bromo-2-deoxy-2-[18F]fluoro-3,5-di-O-benzoyl-α-D-arabinofuranose 在 甲醇 、 sodium methylate 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 0.58h， 生成 1-(2′-deoxy-2′-[¹⁸F]fluoroarabinofuranosyl)cytosine
  参考文献：
  名称：

  MODULAR RADIOCHEMISTRY SYNTHESIS SYSTEM

  摘要：

  一个模块化的化学生产系统包括多个模块，用于从远程位置执行化学反应，特别是放射化学化合物的反应。一个实施例包括一个反应容器，其中包括一个可移动的热源，其相对于反应容器的位置可以从远程位置控制。另一种情况是热源可能固定在某个位置，而反应瓶可以移动进入和移出热源。反应容器有一个或多个密封塞，其相对于反应容器的位置可以从远程位置控制。此外，一个或多个反应容器密封塞可以包括一个或多个通道，用于提供反应物、大气或高压气体、惰性气体、抽真空以及将反应产物从反应瓶中移出和移入，带有密封塞的反应瓶在高压下可操作。该模块化化学生产系统由模块组装而成，每个模块可以包括用于监测和控制各个模块和组装系统的操作条件传感器和控制器，可以从远程位置进行监控和控制。其他模块包括但不限于试剂储存和输送模块、柱层净化模块、微波反应模块、外部质控/分析/净化接口模块、等份取样模块、F-18 干燥模块、浓缩模块、辐射计数模块和毛细管反应器模块。

  公开号：

  US20150329583A1

文献信息

• A novel radiochemical approach to 1-(2'-deoxy-2'-[¹⁸F]fluoro-β-<scp>d</scp>-arabinofuranosyl)cytosine (¹⁸F-FAC)
  作者：Jan-Philip Meyer、Katrin C. Probst、Iuni M. L. Trist、Christopher McGuigan、Andrew D. Westwell

  DOI：10.1002/jlcr.3233

  日期：2014.9

  18F-FAC (1-(2'-deoxy-2'-[18F]fluoro-β-D-arabinofuranosyl)-cytosine) is an important 2'-fluoro-nucleoside-based positron emission tomography (PET) tracer that has been used for in vivo prediction of response to the widely used cancer chemotherapy drug gemcitabine. Previously reported synthetic routes to 18F-FAC have relied on early introduction of the 18F radiolabel prior to attachment to protected cytosine base. Considering the 18F radiochemical half-life (110 min) and the technical challenges of multi-step syntheses on PET radiochemistry modular systems, late-stage radiofluorination is preferred for reproducible and reliable radiosynthesis with in vivo applications. Herein, we report the first late-stage radiosynthesis of 18F-FAC. Cytidine derivatives with leaving groups at the 2'-position are particularly prone to undergo anhydro side-product formation upon heating because of their electron density at the 2-carbonyl pyrimidone oxygen. Our rationally developed fluorination precursor showed an improved reactivity-to-stability ratio at elevated temperatures. 18F-FAC was obtained in radiochemical yields of 4.3–5.5% (n = 8, decay-corrected from end of bombardment), with purities ≥98% and specific activities ≥63 GBq/µmol. The synthesis time was 168 min.

  18F-FAC（1-（2'-脱氧-2'-[18F]氟-β-D-阿糖呋喃糖基）-胞嘧啶）是一种重要的基于2'-氟核苷的正电子发射断层扫描（PET）示踪剂，已用于预测体内对广泛使用的抗癌化疗药物吉西他滨的反应。先前报道的18F-FAC合成路线依赖于在保护的胞嘧啶基团连接之前早期引入18F放射性标记。考虑到18F放射化学半衰期（110分钟）和PET放射化学模块系统中多步骤合成的技术挑战，优选晚期放射氟化以实现可重复且可靠的体内应用放射合成。在此，我们报道了18F-FAC的首次晚期放射合成。由于其在2-羰基嘧啶酮氧上的电子密度，在加热时，在2'-位置具有离去基团的胞嘧啶衍生物特别容易发生脱水副产物的形成。我们合理开发的氟化前体在升高的温度下显示出改进的反应性-稳定性比。18F-FAC的放射化学产率为4.3-5.5%（n = 8，从轰击结束衰减校正），纯度≥98%，比活性≥63 GBq/µmol。合成时间为168分钟。
• AN AUTOMATED, MULTI-POT HIGH-PRESSURE RADIO-SYNTHESIZER FOR PRODUCTION OF PET TRACERS
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：US20160280734A1

  公开（公告）日：2016-09-29

  An automated radiosynthesizer device includes a plurality of reactor assemblies, each reactor assembly being operatively connected to a horizontal actuator for moving the reactor assembly in the horizontal direction and a vertical actuator for moving the reactor assembly in the vertical direction. A plurality of disposable cassettes are disposed above each of the plurality of reactor assemblies, each cassette comprising a lower surface comprising a plurality of sealed and un-sealed gaskets, wherein the un-sealed gaskets are connected to internal fluid paths within the cassette. The device includes a three-axis reagent and gas handling robot disposed above the plurality of cassettes and terminates in a vial gripper and a gas manifold having an inert gas port and a vacuum port. The device includes a control system configured to control the horizontal actuator and vertical actuator of each reactor assembly and the three-axis reagent and gas handling robot.

  一台自动化的放射性同位素合成器设备包括多个反应器组件，每个反应器组件均与水平驱动器和垂直驱动器相连，以在水平和垂直方向上移动反应器组件。多个一次性盒子放置在每个反应器组件上方，每个盒子包括一个下表面，其中包括多个密封和未密封垫圈，未密封垫圈连接到盒子内部的流体通道。该设备包括一个三轴试剂和气体处理机器人，放置在多个盒子上方，终止于一个瓶夹和一个气体集合管，具有惰性气体端口和真空端口。该设备包括一个控制系统，配置为控制每个反应器组件的水平驱动器和垂直驱动器以及三轴试剂和气体处理机器人。
• A microreactor with phase-change microvalves for batch chemical synthesis at high temperatures and pressures
  作者：Xiaoxiao Ma、Wei-Yu Tseng、Mark Eddings、Pei Yuin Keng、R. Michael van Dam

  DOI：10.1039/c3lc50939g

  日期：——

  We present a simple microreactor with dimethyl sulfoxide (DMSO) phase-change valves suitable for performing batch organic chemistry under high temperature and pressure conditions. As a proof of principle, we demonstrate a radiofluorination reaction important in the synthesis of [18F]FAC, a new positron emission tomography biomarker for immune system monitoring and prediction of chemotherapy response. We achieved high radioactivity recovery (97 ± 1%, n = 3) and conversion efficiency (83 ± 1%, n = 3), comparable to that achieved with macroscale systems, but with a volume 30× smaller. This platform overcomes the limitations of previously reported phase-change valves in terms of compatibility with organic chemistry, and extends the range of reaction conditions for carrying out harsh batch chemistry at the microscale.

  我们提出了一种带有二甲亚砜 (DMSO) 相变阀的简单微反应器，适用于在高温高压条件下进行批量有机化学。作为原理证明，我们证明了放射性氟化反应在[18F]FAC的合成中很重要，[18F]FAC是一种新的正电子发射断层扫描生物标志物，用于免疫系统监测和化疗反应预测。我们实现了高放射性回收率（97 ± 1%，n = 3）和转换效率（83 ± 1%，n = 3），与宏观系统实现的效果相当，但体积小了 30 倍。该平台克服了先前报道的相变阀在与有机化学的兼容性方面的局限性，并扩展了在微尺度上进行严苛的批量化学的反应条件范围。
• MODULAR RADIOCHEMISTRY SYNTHESIS SYSTEM
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：US20150329583A1

  公开（公告）日：2015-11-19

  A modular chemical production system includes multiple modules for performing a chemical reaction, particularly of radiochemical compounds, from a remote location. One embodiment comprises a reaction vessel including a moveable heat source with the position thereof relative to the reaction vessel being controllable from a remote position. Alternatively the heat source may be fixed in location and the reaction vial is moveable into and out of the heat source. The reaction vessel has one or more sealing plugs, the positioning of which in relationship to the reaction vessel is controllable from a remote position. Also the one or more reaction vessel sealing plugs can include one or more conduits there through for delivery of reactants, gases at atmospheric or an elevated pressure, inert gases, drawing a vacuum and removal of reaction end products to and from the reaction vial, the reaction vial with sealing plug in position being operable at elevated pressures. The modular chemical production system is assembled from modules which can each include operating condition sensors and controllers configured for monitoring and controlling the individual modules and the assembled system from a remote position. Other modules include, but are not limited to a Reagent Storage and Delivery Module, a Cartridge Purification Module, a Microwave Reaction Module, an External QC/Analysis/Purification Interface Module, an Aliquotting Module, an F-18 Drying Module, a Concentration Module, a Radiation Counting Module, and a Capillary Reactor Module.

  一个模块化的化学生产系统包括多个模块，用于从远程位置执行化学反应，特别是放射化学化合物的反应。一个实施例包括一个反应容器，其中包括一个可移动的热源，其相对于反应容器的位置可以从远程位置控制。另一种情况是热源可能固定在某个位置，而反应瓶可以移动进入和移出热源。反应容器有一个或多个密封塞，其相对于反应容器的位置可以从远程位置控制。此外，一个或多个反应容器密封塞可以包括一个或多个通道，用于提供反应物、大气或高压气体、惰性气体、抽真空以及将反应产物从反应瓶中移出和移入，带有密封塞的反应瓶在高压下可操作。该模块化化学生产系统由模块组装而成，每个模块可以包括用于监测和控制各个模块和组装系统的操作条件传感器和控制器，可以从远程位置进行监控和控制。其他模块包括但不限于试剂储存和输送模块、柱层净化模块、微波反应模块、外部质控/分析/净化接口模块、等份取样模块、F-18 干燥模块、浓缩模块、辐射计数模块和毛细管反应器模块。