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Automated Synthesis of ( rac )‐, ( R )‐, and ( S )‐[ 18 F]Epifluorohydrin and Their Application for Developing PET Radiotracers Containing a 3‐[ 18 F]Fluoro‐2‐hydroxypropyl Moiety
Author(s) -
Fujinaga Masayuki,
Ohkubo Takayuki,
Yamasaki Tomoteru,
Zhang Yiding,
Mori Wakana,
Hanyu Masayuki,
Kumata Katsushi,
Hatori Akiko,
Xie Lin,
Nengaki Nobuki,
Zhang MingRong
Publication year - 2018
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201800359
Subject(s) - chemistry , moiety , nucleophile , in vivo , stereochemistry , in vitro , radiochemistry , catalysis , organic chemistry , biochemistry , microbiology and biotechnology , biology
To introduce the 3‐[ 18 F]fluoro‐2‐hydroxypropyl moiety into positron emission tomography (PET) radiotracers, we performed automated synthesis of ( rac )‐, ( R )‐, and ( S )‐[ 18 F]epifluorohydrin ([ 18 F] 1 ) by nucleophilic displacement of ( rac )‐, ( R )‐, or ( S )‐glycidyl tosylate with 18 F − and purification by distillation. The ring‐opening reaction of ( R )‐ or ( S )‐[ 18 F] 1 with phenol precursors gave enantioenriched [ 18 F]fluoroalkylated products without racemisation. We then synthesised ( rac )‐, ( R )‐, and ( S )‐ 2‐{5‐[4‐(3‐[ 18 F]fluoro‐2‐hydroxypropoxy)phenyl]‐2‐oxobenzo[ d ]oxazol‐3(2 H )‐yl}‐ N ‐methyl‐ N ‐phenylacetamide ([ 18 F] 6 ) as novel radiotracers for the PET imaging of translocator protein (18 kDa) and showed that ( R )‐ and ( S )‐[ 18 F] 6 had different radioactivity uptake in mouse bone and liver. Thus, ( rac )‐, ( R )‐, and ( S )‐[ 18 F] 1 are effective radiolabelling reagents and can be used to develop PET radiotracers by examining the effects of chirality on their in vitro binding affinities and in vivo behaviour.