唐刚华, 张岚, 唐小兰, 汪勇先, 尹端沚. 6-氟-L-多巴合成及其对映纯度测定的研究J. 药学学报, 2001, 36(10): 739-742.
引用本文: 唐刚华, 张岚, 唐小兰, 汪勇先, 尹端沚. 6-氟-L-多巴合成及其对映纯度测定的研究J. 药学学报, 2001, 36(10): 739-742.
TANG Gang-hua, ZHANG Lan, TANG Xiao-lan, WANG Yong-xian, YIN Duan-zhi. SYNTHESIS AND DETERMINATION FOR ENANTIOMERIC PURITY OF 6-FLUORO-L-DOPAJ. Acta Pharmaceutica Sinica, 2001, 36(10): 739-742.
Citation: TANG Gang-hua, ZHANG Lan, TANG Xiao-lan, WANG Yong-xian, YIN Duan-zhi. SYNTHESIS AND DETERMINATION FOR ENANTIOMERIC PURITY OF 6-FLUORO-L-DOPAJ. Acta Pharmaceutica Sinica, 2001, 36(10): 739-742.

6-氟-L-多巴合成及其对映纯度测定的研究

SYNTHESIS AND DETERMINATION FOR ENANTIOMERIC PURITY OF 6-FLUORO-L-DOPA

  • 摘要: 目的 合成6-氟-L-多巴(6-FDOPA) ,并测定其对映纯度。方法 以硝基藜芦醛(2)为原料,经亲核取代、还原碘化、手性相转移催化烷基化等多步反应得新化合物2-(2-氟-4,5-二甲氧苄基)-N-(二苯基甲叉)甘氨酸叔丁酯(8) ,8经水解反应制备终产物6-FDOPA ,用手性流动相和反相C18柱的HPLC法测定其对映纯度。结果 合成6-氟-L-多巴总反应时间少于90min ,总产率约为33% ,对映纯度大于95%。结论 可大量合成6-FDOPA ,使自动合成6-18F-L-多巴成为可能。为6-18F-L-多巴的放射化学合成及其对映纯度的测定提供了可靠的技术

     

    Abstract: AIM To study the synthesis and determination for enantiomeric purity of 6-fluoro-L-3,4-dihydroxyphenylalanine (6-fluoro-L-DOPA, 6-FDOPA). METHODS 2-(2-Fluoro-4,5-dimethoxybenzyl)-N-(diphenylmethylene)glycine tert-butyl ester (8), a new compound, was synthesized from the starting material nitroveratraldehyde via the nucleophilic displacement, reductive iodination, and chiral catalytic phase transfer alkylation, and 6 FDOPA was prepared from hydrolysis of 8. The enantiomeric purity of 6-FDOPA was determined by HPLC method using a chiral mobil phase and reversed phase C18 column. RESULTS The total time of synthesis was less than 90 min, the overall chemical yield from potassium fluoride was about 33%, and the enantiomeric purity was above 95%. CONCLUSION Large scale production of 6-FDOPA and automatic synthesis of 6-18Ffluoro-L-DOPA with excellent chemical and entiomeric purity are available. The practical technique was provided for the radiochemical synthesis and entiomeric purity of 6-18Ffluoro-L-DOPA.

     

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