Universität zu Köln

Craig, Austin (2021). Preparation of Labeled Aromatic Amino Acids via Late-Stage 18F-Fluorination of Chiral Nickel and Copper Complexes. PhD thesis, Universität zu Köln.

Preview

PDF Austin Craig Dissertation.pdf - Accepted Version Download (17MB) | Preview

Abstract

18F-Labeled aromatic amino acids (AAA) are valuable tools for the detection of oncological and neurological disorders using positron emission tomography (PET). Despite their potential, only a minority of AAA tracers have been applied in clinical diagnostics due to the lack of efficient radiosynthetic protocols available. This work presents a practical procedure for the preparation of ten structurally diverse 18F-labeled AAA via alcohol-enhanced Cu-mediated radiofluorination of chiral Ni- or Cu-[(Benzylprolyl)amino]phenone-glycine/alanine (Ni/Cu-BPX) auxiliaries. Herein, chiral Ni-BPX (also known as “Belokon”) complexes, which serve as easily-removable dual-protecting group functionalities, are demonstrated to be ideal for synthetic and radiosynthetic purposes. Accordingly, the application of (S)-Ni-BPX complexes towards several synthetically challenging α-methyl-substituted-AAA (α-Me-AAA) tracers is reported. In addition, the employment of (R)-Ni-BPX enabled the novel 3-(R)-[18F]fluorophenylalanine (3-(R)-[18F]FPhe) tracer to be accessed. The applicability of Cu-BPX complexes towards 18F-labeled AAA production has also been described for the first time. The application of Cu- instead of Ni-complexes in association with Cu-mediated radiofluorination advantageously requires only a single trace metal to be determined for 18F-labeled AAA products, in order to fulfill the requirements of current good manufacturing production (cGMP). The methodology, which furnishes 18F-labeled AAAs in high radiochemical yields (RCY), and excellent enantiomeric and radiochemical purities (RCP), provides significant advancements compared to literary procedures and paves the way for future AAA tracer preparations using the approach outlined herein. In addition, 3-[18F]fluorophenylserine (3-[18F]FPheSer), a potential noradrenergic system imaging agent, was successfully prepared. As the noradrenergic system is adversely affected by neurological disorders, 3-[18F]FPheSer–PET may afford invaluable diagnostic information. Finally, a one-step preparation of the promising prosthetic group 4-[18F]fluorophenylboronic acid ([18F]FPBA), previously demonstrated to be suitable for radiolabeling of biopolymers, has been developed.

Item Type:	Thesis (PhD thesis)
Creators:	Creators Email ORCID ORCID Put Code Craig, Austin austin.craig@ucdconnect.ie UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-355675
Date:	8 February 2021
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Außeruniversitäre Forschungseinrichtungen > Forschungszentrum Jülich
Subjects:	Chemistry and allied sciences Life sciences
Uncontrolled Keywords:	Keywords Language 18F-Labeled Aromatic Amino Acids English Cu-Mediated radiofluorination English Ni-BPB Cu-BPB complexes English
Date of oral exam:	3 July 2020
Referee:	Name Academic Title Neumaier, Bernd Prof. Dr.
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/35567