Automated Synthesis of (rac)‐, (R)‐, and (S)‐[18F]Epifluorohydrin and Their Application for Developing PET Radiotracers Containing a 3‐[18F]Fluoro‐2‐hydroxypropyl Moiety. (25th July 2018)

• Record Type: Journal Article
• Authors: Fujinaga, Masayuki; Ohkubo, Takayuki; Yamasaki, Tomoteru; Zhang, Yiding; Mori, Wakana; Hanyu, Masayuki; Kumata, Katsushi; Hatori, Akiko; Xie, Lin; Nengaki, Nobuki; Zhang, Ming‐Rong
• Is Part Of: ChemMedChem. Volume 13:Number 16(2018)
• Page Start: 1723
• Page End: 1731
• Publication Date: 2018-07-25
• Subjects: automated synthesis -- [18F]epifluorohydrin -- 18F-fluoroalkylation -- imaging agents -- translocator protein; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201800359
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract: 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. Abstract : PET project : We performed automated synthesis of ( rac )‐, ( R )‐, and ( S )‐[ 18 F]epifluorohydrin ([ 18 F]1 ) by reaction of ( rac )‐, ( R )‐, or ( S )‐glycidyl tosylate (2 ) with 18 F − . The reaction of ( R )‐ or ( S )‐[ 18 F]1 with phenol precursors gave enantiomeric 18 F‐fluoroalkylated products without racemisation. ( rac )‐, ( R )‐, and ( S )‐[ 18 F]1 are effective radiolabelling agents and can be used to develop positron emission tomography radiotracers containing the 3‐[ 18 F]fluoro‐2‐hydroxypropyl group.