Organomediated Enantioselective ¹⁸F Fluorination for PET Applications

Abstract

The first organomediated asymmetric (18)F fluorination has been accomplished using a chiral imidazolidinone and [(18)F]N-fluorobenzenesulfonimide. The method provides access to enantioenriched (18)F-labeled α-fluoroaldehydes (>90% ee), which are versatile chiral (18)F synthons for the synthesis of radiotracers. The utility of this process is demonstrated with the synthesis of the PET (positron emission tomography) tracer (2S,4S)-4-[(18)F]fluoroglutamic acid.

Chemie der Positronenemissionstomographie: Aktuelle Fortschritte bei 11C‐, 18F‐, 13N‐ und 15O‐Markierungsreaktionen

“…2015 entwickelten Gouverneur et al. eine organokatalytische enantioselektive 18 F‐Fluorierung von Aldehyden mit [ 18 F]NFSI (Schema B) . Die Eintopf‐Reaktion begann mit einem chiralen Imidazolidinon und [ 18 F]NFSI, woran sich die Oxidation von CHO zu COOH und die Entschützung anschlossen und 18 F‐markierte Aminosäuren erhalten wurden.…”

Chemistry for Positron Emission Tomography: Recent Advances in 11C‐, 18F‐, 13N‐, and 15O‐Labeling Reactions

“…[202,203] 18 F-fluorination, albeit in low RCY and accompanied by undesired regioisomers (Scheme 35 A1). [206] The" one-pot" reaction commenced with ac hiral imidazolidinone and [ 18 F]NFSI, followed by oxidation of CHO to COOH and then deprotection to provide 18 F-labeled amino acids.F or example,( 2 S,4S)-4-[ 18 F]fluoroglutamic acid was synthesized in 62 %R CC with high enantioselectivity (> 99 % ee)a nd high diastereoselectivity (19:1 d.r). [205] Ther ecent development of [ 18 F]F 2 -derived reagents,s uch as [ 18 F]NFSI, provided an ew opportunity for enantio-and diastereoselective 18 F-fluorination.…”

Recent Advances of Direct Incorporation of Fluorine-Containing Groups and 18F-Labeling Methods

“…最近 Gouverneur 等 [116] 报道了首例有机催化的不对 称 18 F-氟化作用. 该反应使用手性咪唑烷酮作为催化剂, [ 18 F]N-氟代双苯磺酰胺( [18 F]NFSI)作为氟来源 [117] , 得到 18 [116] . 该课题组 [118] 通过合成 PET 示踪剂(2S,4S)-4-[ 18…”