[18F]-L-3,4-dihydroxy-5-fluorophenylalanine

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: [18F]-L-3,4-dihydroxy-5-fluorophenylalanine
• 英文别名: [18F]-5-fluoro-L-DOPA；[18F]5-fluoro-L-DOPA；[18F]5-FDOPA；(2S)-2-amino-3-(3-(18F)fluoranyl-4,5-dihydroxyphenyl)propanoic acid
• 化学式: C₉H₁₀FNO₄
• 分子量: 214.183
• InChiKey: HAAXTGIFJHNHSX-RPDRGXCHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.6
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  104
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  左旋多巴 在 [¹⁸F]fluoride 作用下， 以 溶剂黄146 、 三氟乙酸 为溶剂， 反应 1.08h， 生成 [18F]-L-3,4-dihydroxy-2-fluorophenylalanine 、 [18F]-L-3,4-dihydroxy-5-fluorophenylalanine
  参考文献：
  名称：

  溶剂对L-DOPA亲电子元素氟化的影响的放射化学和NMR光谱研究：[ ] 5-氟-L-DOPA的合成

  摘要：

  已经开发出在不同溶剂中3,4-二羟基苯基-L-丙氨酸（L-DOPA）进行亲电氟化反应中氟的反应性和选择性的差异，可生产出m Ci量的[ ] 5-氟-L-DOPA。质子和光谱法已被证明，尽管弱酸（三氟乙酸，冰醋酸和甲酸中的10％三氟乙酸）中L-DOPA的亲电氟化取向受环上给电子的OH基团的影响，L-DOPA在强酸（HF和HF / BF 3）中的亲电氟化取向主要受侧链影响。

  DOI：

  10.1016/s0022-1139(99)00123-2

文献信息

• Trifluoromethanesulfonic acid, an alternative solvent medium for the direct electrophilic fluorination of DOPA: new syntheses of 6-[18F]fluoro-L-DOPA and 6-[18F]fluoro-D-DOPA
  作者：Babak Behnam Azad、Raman Chirakal、Gary J. Schrobilgen

  DOI：10.1002/jlcr.1454

  日期：2007.12

  Previous work from this laboratory has shown that the direct fluorination of 3, 4-dihydroxy-phenyl-L-alanine (L-DOPA) in anhydrous HF (aHF) or BF3/HF with F2 is an efficient method for the synthesis of 6-fluoro-L-DOPA. Since then, 18F-labeled 6-fluoro-L-DOPA ([18F]6-fluoro-L-DOPA) has been used to study presynaptic dopaminergic function in the human brain and to monitor gastrointestinal carcinoid tumors. This work demonstrates that the reactivity and selectivity of F2 toward L-DOPA in CF3SO3H is comparable with that in aHF. This new synthetic procedure has led to the production of [18F]fluoro-L-DOPA and [18F]fluoro-D-DOPA isomers in 17±2% radiochemical yields (decay corrected with respect to [18F]F2). The 2- and 6-FDOPA isomers were separated by HPLC and subsequently characterized by 19F NMR spectroscopy. The corresponding [18F]-FDOPA enantiomers have been obtained in clinically useful quantities by a synthetic approach that avoids the use of aHF. Copyright © 2007 John Wiley & Sons, Ltd.

  该实验室之前的研究表明，在无水氢氟酸（aHF）或 BF3/HF 中用 F2 直接氟化 3，4-二羟基苯基-L-丙氨酸（L-DOPA）是合成 6-氟-L-DOPA 的有效方法。此后，18F 标记的 6-氟-L-DOPA（[18F]6-氟-L-DOPA）被用于研究人脑突触前多巴胺能功能和监测胃肠道类癌。 这项研究表明，F2 在 CF3SO3H 中对 L-DOPA 的反应性和选择性与在 aHF 中相当。这一新的合成过程产生了[18F]氟-L-DOPA和[18F]氟-D-DOPA异构体，放射化学收率为17±2%（相对于[18F]F2的衰变校正）。2-FDOPA 和 6-FDOPA 异构体通过高效液相色谱法分离，随后通过 19F NMR 光谱法进行表征。相应的 [18F]-FDOPA 对映异构体已通过避免使用 aHF 的合成方法获得了临床有用的数量。Copyright © 2007 John Wiley & Sons, Ltd. All Rights Reserved.
• Vasdev; Chirakal; Schrobilgen, Journal of labelled compounds and radiopharmaceuticals, 1999, vol. 42, # SUPPL. 1, p. S486-S488
  作者：Vasdev、Chirakal、Schrobilgen、Nahmias

  DOI：——

  日期：——
• The effect of aromatic fluorine substitution in l-DOPA on the in vivo behaviour of []2-, []5- and []6-fluoro-l-DOPA in the human brain
  作者：Raman Chirakal、Neil Vasdev、Marie-Claude Asselin、Gary J Schrobilgen、Claude Nahmias

  DOI：10.1016/s0022-1139(02)00025-8

  日期：2002.5

  Remarkable differences in the human in vivo behaviour of each of the three [F-18]-labelled ring fluorinated isomers of L-dihydroxyphenylalanine (L-DOPA) are presented. Unlike [F-18]2-fluoro-L-DOPA, which did not appear to cross the blood brain barrier, [F-18]5-fiuoro-L-DOPA appears to be taken up and cleared from the cerebellum and the striata. In contrast with the 2- and 5-fluoro isomers of L-DOPA, radioactivity derived after injection of [F-18]6-fluoro-L-DOPA is specifically retained in the striata. The present study is the first direct comparison of the time course and distribution of radioactivity in the human brain after intravenous injections of [F-18]2-, [F-18]5- and [(18)]F6-fluoro-L-DOPA. (C) 2002 Elsevier Science B.V. All rights reserved.
• Radiochemical and NMR spectroscopic investigation of the solvent effect on the electrophilic elemental fluorination of L-DOPA: synthesis of []5-fluoro-L-DOPA
  作者：Raman Chirakal、Neil Vasdev、Gary J. Schrobilgen、Claude Nahmias

  DOI：10.1016/s0022-1139(99)00123-2

  日期：1999.10

  Differences in reactivity and selectivity of fluorine in the electrophilic fluorination of 3,4-dihydroxy phenyl-L-alanine (L-DOPA) in different solvents have been exploited to produce mCi quantities of []5-fluoro-L-DOPA. Proton and spectroscopy have been used to show that, while the orientation of electrophilic fluorination of L-DOPA in weak acids (trifluoroacetic acid, 10% trifluoroacetic acid in

  已经开发出在不同溶剂中3,4-二羟基苯基-L-丙氨酸（L-DOPA）进行亲电氟化反应中氟的反应性和选择性的差异，可生产出m Ci量的[ ] 5-氟-L-DOPA。质子和光谱法已被证明，尽管弱酸（三氟乙酸，冰醋酸和甲酸中的10％三氟乙酸）中L-DOPA的亲电氟化取向受环上给电子的OH基团的影响，L-DOPA在强酸（HF和HF / BF 3）中的亲电氟化取向主要受侧链影响。