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Synthesis of N.C.A. cis‐ and trans‐4‐[ 18 F]fluoro‐l‐proline, radiotracers for PET‐investigation of disordered matrix protein synthesis
Author(s) -
Hamacher Kurt
Publication year - 1999
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/(sici)1099-1344(199912)42:12<1135::aid-jlcr267>3.0.co;2-3
Subject(s) - chemistry , radiosynthesis , proline , hydrolysis , yield (engineering) , nucleophile , toluene , high performance liquid chromatography , derivatization , acid hydrolysis , amino acid , extraction (chemistry) , stereochemistry , chromatography , organic chemistry , catalysis , in vivo , biochemistry , materials science , microbiology and biotechnology , metallurgy , biology
A radiosynthesis of n.c.a. (2S,4R)‐4‐[ 18 F]fluoroproline (trans‐configuration) and its disastereomer (2S,4S)‐4‐[ 18 F]fluoroproline (cis‐configuration) has been developed. It allows the routine production of up to 18 GBq of product for clinical purposes in a remote controlled system. The 18 F‐labelled amino acids were prepared via cryptate mediated n.c.a. nucleophilic 18 F‐fluorination starting from the corresponding N‐Boc‐4‐(toluene‐sulfonyloxy)proline methylester. N‐deprotection and ester hydrolysis takes place under acidic conditions in presence of trifluoromethanesulfonic acid. HPLC‐purification combined with on‐line solid phase extraction yielded the diastereomerically pure 4‐[ 18 F]fluoroprolines within 90 min with a radiochemical yield of 36±7% (n=52). Configuration of both isomers was confirmed by comparison with standard compounds which were synthesized via fluorination of the related oxazolidinones with diethylamino sulfurtrifluoride, starting from (2S,4S)‐ and (2S,4R)‐4‐hydroxy proline, respectively. Copyright © 1999 John Wiley & Sons, Ltd.