Synthesis of Fluoro-substituted Anthraquinones as Potential Tumor Imaging Agents for Positron Emission Tomography

• Main Authors: Hui-Xian Liu, 劉惠賢
• Other Authors: Ling-Wei Hsin
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/30306542422165511196

碩士 === 臺灣大學 === 藥學研究所 === 98 === Based on the results of a series of studies on the pharmacological activity of fluoroaminoqnthraquinones in our laboratory, fluorine-18 labeled compound 48 was selected to be synthesized for the application of positron emission tomography in this study. The synthetic principle is to introduce fluorine-18 at the terminal step of the whole synthetic route and to optimize the total reaction time, as to minimize the decay of radioactive fluorin-18. Theoretically, this can be achieved by two synthetic methods: direct nucleophilic substitution through introducing fluorine-18 into precursor 2 and indirect substitution through introducing fluoring-18 labeled prosthetic group into precursor 1 to get the fluorine-18 labeled target compound 48. Precursor 1 (49), precursor 2 (39) and fluorination standard compound 38 and 48 were successfully synthesized in this study. First, the terminal hydroxyl group of commercial available starting material, N-(3-hydroxylpropyl)ethylenediamine, was protected with TBDMS protecting group and then bound to the Leucoquinizarin by condensation and oxidation reactions. The amino groups (R1 and R3) were protected by triphenylmethyl protecting group and then the TBDMS protecting group was removed by potassium fluoride and Kryptofix 222. Eventually, precursor 39 was obtain by Mesylation. Whereas for precursor 49, standard compound 48 and standard compound 38, the amino group (R2) in ethylenediamine was protected by Teoc protecting group and bound to Leucoquinizarin by condensation and oxidation reactions. Then, then the amino group (R1) was protected by triphenylmethyl protecting group and the Teoc protecting group was removed by potassium fluoride and Kryptofix 222 to get precursor 49. The standard compound 48, yield: 26%, was obtained from precursor 49 by nucleophilic substitution with the prosthetic group, 3-fluoropropyl-p-toluene sulfonate. Finally, the amino group in standard compound 48 was protected by triphenylmethyl protecting group to gain fluorination standard compound 38.