Baeyer-Villiger oxidation tuned to chemoselective conversion of non-activated [ F]fluorobenzaldehydes to [ F]fluorophenols.

A reaction pathway via oxidation of [ F]fluorobenzaldehydes offers a very useful tool for the no-carrier-added radiosynthesis of [ F]fluorophenols, a structural motive of several potential radiopharmaceuticals. A considerably improved chemoselectivity of the Baeyer-Villiger oxidation (BVO) towards phenols was achieved, employing 2,2,2-trifluoroethanol as reaction solvent in combination with Oxone or m-CPBA as oxidation agent. The studies showed the necessity of H SO addition, which appears to have a dual effect, acting as catalyst and desiccant.

Radiosynthesis of 4-[(18)F]fluoro-L-tryptophan by isotopic exchange on carbonyl-activated precursors.

Several (18)F-labeled aromatic amino acids have been developed primarily for tumor imaging with positron-emission-tomography (PET). Also, (18)F-labeled tryptophan derivatives were synthesized by electrophilic (18)F-fluorination or by introducing a [(18)F]fluoroalkyl group. Here, a 3-step method for a nucleophilic radiosynthesis of 4-[(18)F]fluoro-L-tryptophan was developed.

A three-step radiosynthesis of 6-[(18) F]fluoro-L-meta-tyrosine starting with [(18) F]fluoride.

The radiosynthesis of 6-[(18)  F]fluoro-L-m-tyrosine has generally been performed by electrophilic radiofluorination, which exhibits several drawbacks. In the present work, a three-step radiochemical synthesis is described starting from [(18)  F]fluoride. The synthetic sequence, including isotopic exchange, Baeyer-Villiger oxidation, and hydrolysis, were examined comparing four fluorobenzophenone derivatives as labeling precursors.

Bis(4-benzyloxyphenyl)iodonium salts as effective precursors for the no-carrier-added radiosynthesis of 4-[¹⁸F]fluorophenol.

4-[¹⁸F]Fluorophenol is a very useful intermediate compound for building-up more complex molecules bearing a 4-[¹⁸F]fluorophenoxy moiety. Bis(4-benzyloxyphenyl)iodonium salts proved very effective as labeling precursors for the radiosynthesis of this compound in no-carrier-added form. Starting from the bromide salt and performing the radiofluorination by conventional heating, 4-[¹⁸F]fluorophenol was obtained in an overall RCY of 43 ± 12% while a yield of 52 ± 3% was achieved more reliably starting from the tosylate salt and employing microwave heating.

Enantiospecific synthesis of 2-[18F]fluoro-L-phenylalanine and 2-[18F]fluoro-L-tyrosine by isotopic exchange.

2-[(18)F]Fluoro-L-phenylalanine and 2-[(18)F]fluoro-L-tyrosine have been developed as promising radiopharmaceuticals for molecular imaging using positron emission tomography (PET). However, the lack of a convenient radiosynthetic pathway has limited their practical use. In this work a new three-step nucleophilic synthesis of these compounds starting from [(18)F]fluoride is described.