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Comparison of synthesis yields of 3′‐deoxy‐3′‐[ 18 F]fluorothymidine by nucleophilic fluorination in various alcohol solvents
Author(s) -
Lee Sang Ju,
Oh Seung Jun,
Chi Dae Yoon,
Lee Byoung Se,
Ryu Jin Sook,
Moon Dae Hyuk
Publication year - 2008
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.1478
Subject(s) - chemistry , alcohol , nucleophile , yield (engineering) , solvent , medicinal chemistry , trifluoromethyl , primary alcohol , ethanol , nucleophilic substitution , nuclear chemistry , organic chemistry , methanol , catalysis , materials science , alkyl , metallurgy
[ 18 F]Fluorothymidine ([ 18 F]FLT) is synthesized with a high radiochemical yield by nucleophilic substitution in protic solvent. In this study, we compared [ 18 F]fluorination yields of [ 18 F]fluorothymidine ([ 18 F]FLT) in various alcohol solvents: 3,3‐dimethyl‐1‐butanol, 2‐trifluoromethyl‐2‐propanol, t ‐BuOH (2‐methyl‐2‐propanol), t ‐amyl alcohol (2‐methyl‐2‐butanol), thexyl alcohol (2,3‐dimethyl‐2‐butanol) and 3,3‐dimethyl‐2‐butanol. We used 5′‐ O ‐DMTr‐2′‐deoxy‐3′‐ O ‐nosyl‐β‐D‐threopentofuranosyl)‐3‐ N ‐BOC‐thymine as a precursor for [ 18 F]fluorination. [ 18 F]F − was eluted with TBAHCO 3 solution after trapping [ 18 F]F − on a PS‐HCO 3 cartridge. [ 18 F]fluorination was performed at 100°C for 5–30 min using 20 mg of the precursor. [ 18 F]fluorination and radiochemical yields of [ 18 F]FLT were evaluated by radioTLC. [ 18 F]fluorination yields were dependent on the solvent used. All tertiary alcohol solvents, except 2‐trifluoromethyl‐2‐propanol, showed >85% of [ 18 F]fluorination yields, whereas primary and secondary alcohols showed 26.3–71.8%. The highest yield of 94.1±4.4% was obtained with thexyl alcohol after [ 18 F]fluorination for 5 min. Automated synthesis with t ‐amyl alcohol resulted in high synthetic yields of 64.6±6.1% after high‐performance liquid chromatography purification ( n =43). The use of tertiary alcohol as a solvent provides high radiochemical yields of [ 18 F]FLT. Copyright © 2008 John Wiley & Sons, Ltd.