Radiolabeling of protected tryptophan with [18F]fluoromethyl tosylate: Formation of [18F]fluoromethyl ester of tryptophan instead of 1-N-[18F]fluoromethyl tryptophan methylester

T K Venkatachalam; D H R Stimson; K Frisch; G K Pierens; R Bhalla; D C Reutens

doi:10.1016/j.apradiso.2019.06.039

Radiolabeling of protected tryptophan with [¹⁸F]fluoromethyl tosylate: Formation of [¹⁸F]fluoromethyl ester of tryptophan instead of 1-N-[¹⁸F]fluoromethyl tryptophan methylester

Appl Radiat Isot. 2019 Oct:152:172-179. doi: 10.1016/j.apradiso.2019.06.039. Epub 2019 Jun 27.

Authors

T K Venkatachalam¹, D H R Stimson², K Frisch³, G K Pierens², R Bhalla², D C Reutens²

Affiliations

¹ Centre for Advanced Imaging, University of Queensland, 4072, Brisbane, Australia. Electronic address: t.venkatachalam@uq.edu.au.
² Centre for Advanced Imaging, University of Queensland, 4072, Brisbane, Australia.
³ Aarhus Kommune Hospital, Aarhus, Denmark.

PMID: 31349203
DOI: 10.1016/j.apradiso.2019.06.039

Abstract

The reaction of [¹⁸F]fluoromethyl tosylate with methyl(tert-butoxycarbonyl)-l-tryptophanate results in formation the O-alkylated ester of the tryptophan instead of alkylation of the indole nitrogen of tryptophan as initially anticipated. Treatment of protected tryptophan with NaH in dimethyl formamide (DMF) along with [¹⁸F]fluoromethyl tosylate at 130°C results in the formation of [¹⁸F]fluoromethyl(tert-butoxycarbonyl)-l-tryptophanate. Preferential formation of the O-alkylated product is postulated to be due to the hydrolysis of the ester. Confirmation of the O-alkylation was obtained by synthesizing the [¹⁹F]fluoromethyl(tert-butoxycarbonyl)-l-tryptophanate insitu and examining its NMR characteristics using multiple NMR techniques. Similar results were also obtained when reacting Boc-tryptophan-N-carboxyanhydride precursor with fluoromethyl tosylate.

Keywords: Alkylation; Challenges; Fluoromethyl tosylate; Protected tryptophan; Radiolabeling.