Asian Journal of Nuclear Medicine
亞洲核醫學雜志

Volume 2 Number 1, March 2002
Abstract

親核對映選擇結合手性催化劑相轉移烷基化法合成無載體6-[18F]-L-多巴

唐剛華12 張嵐2,唐小蘭1,王明芳1,汪勇先2,黃祖漢1,尹端止2
1第一軍醫大學南方醫院南方PET中心,廣州 510515,中國
2中國科學院上海原子核研究所放藥中心,上海 201800,中國

目的 研製無載體6-[18F]-L-多巴。方法 以硝基藜蘆醛為原料,經親核取代氟化、還原碘化、手性相轉移催化劑烷基化、水解及半制備型HPLC純化等步驟合成6-[18F]-L-多巴,用手性流動相結合C18柱HPLC法測定終產物6-[18F]-L-多巴的對映純度。結果 經時間衰減校正,制備的6-[18F]-L-多巴總放化產率為5-28%,總放化合成時間為90-120 min,放化純度大於98%,對映純度大於95%。結論 為制備6-[18F]-L-多巴及其他[18F]-L-氨基酸提供有效的合成路線,為測定6-[18F]-L-多巴及其他[18F]-L-氨基酸類似物的對映純度提供簡便實用的方法。

關鍵詞 6-[18F]-L-多巴;親核氟化;手性相轉移催化劑烷基化;對映純度;手性流動相HPLC法

Nucleophilic enantioselective synthesis of no-carrier-added 6-[18F]fluoro-L-DOPA via chiral catalytic phase-transfer alkylation

Ganghua Tang1, 2, Lan Zhang2, Xiaolan Tang1, Mingfang Wang1, Yongxian Wang2, Zuhan Huang1, Duanzhi Yin2
1Nanfang PET Centre, Nan Fang Hospital, First Military Medical University, Guangzhou 510515, China
2Radiopharmaceutical Research Centre, Shanghai Institute of Nuclear Research, the Chinese Academy of Sciences, Shanghai 201800, China

Objective To prepare the no-carrier-added 6-[18F]fluoro-L-DOPA (FDOPA). Methods FDOPA was synthesized from the starting material 6-nitroveratraldehyde via nucleophilic displacement fluorination, reductive iodionation, chiral phase-transfer catalyst (PTC) alkylation, hydrolysis and purification by preparative high-pressure liquid chromatography(HPLC), and the enantiomeric purity was determined by HPLC analysis on C18-column using a chiral mobile phase. Results The radiochemical yield of FDOPA from [18F]fluoride was 5-28% with decay-correction, and the whole synthesis time was 90-120 min. The radiochemical purity was more than 98% and the enantiomeric purity was above 95%. Conclusion A highly nucleophilic regioselective synthesis of FDOPA by PTC approach provides an efficient and flexible synthetic route to FDOPA and other [18F]fluoro-L-aromatic amino acids. HPLC analysis using a chiral mobile phase affords a simple and practical method for measuring enantiomeric purity of FDOPA and other [18F]fluoro-L-amino acids.

Key Words: 6-[18F]Fluoro-L-DOPA; Nucleophilic displacement; Chiral catalytic phase-transfer alkylation; Enantiomeric purity; HPLC analysis using chiral mobile phase



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