The Effect of Reaction Media and Phase Transfer Catalyst on the Fluorination Yield and Enantiomeric Purity in Asymmetric Synthesis of O-(2'-[¹⁸F]fluoroethyl)-LTyrosine ([¹⁸F]FET)

Title:The Effect of Reaction Media and Phase Transfer Catalyst on the Fluorination Yield and Enantiomeric Purity in Asymmetric Synthesis of O-(2'-[¹⁸F]fluoroethyl)-LTyrosine ([¹⁸F]FET)

Volume: 17 Issue: 19

Author(s): Raisa Krasikova, Victoria Orlovskaya, Maria Stepanova and Olga Fedorova

Affiliation:

Keywords: ¹⁸F, fluorine-18 radiolabeling, Protic solvents fluorination, O-(2-[¹⁸F]fluoroethyl)-L-tyrosine, [¹⁸F]FET, Asymmetric synthesis, Brain tumors PET imaging.

Abstract: Due to favourable in-vivo characteristics, the long half-life of ¹⁸F (110 min) allowing for remote-site delivery and its high specificity, O-(2’-[¹⁸F]fluoroethyl)-L-tyrosine ([¹⁸F]FET) has gained increased importance for molecular imaging of cerebral tumors. Consequently, the development of simple and efficient production strategies for FET could be an important step to further improve the cost-effective availability of FET in the clinical environment. An earlier developed labeling approach using a chiral Ni^II complex of an alkylated (S)-tyrosine Schiff base, Ni-(S)-BPB-(S)-Tyr-OCH₂CH₂OTs (II) as a synthesis precursor provided a good means of preparing FET in high enantiomeric purity of 94-97%, but in moderate RCY. The aim of this study was to improve the ¹⁸F-fluorination efficiency of (II) by varying fluorinations conditions: reaction media (non protic and protic solvents), PTC/base system and temperature. A very high ¹⁸F-fluoride incorporation rate into (II) was achieved in kryptofix-mediated fluorinations in DMSO, however this route did not allow FET in high and reproducible enantiomeric purity that is essential for application in PET human studies. The attempted ¹⁸F-fluorination of (II) in tert-alcohols resulted in poor (t-BuOH) or moderate (t-amyl alcohol) incorporation rates and associated with difficulties in the process automation. From our current results we may conclude that the earlier developed acetonitrile/K2.2.2 remains the most appropriate solvent/ catalyst combination for use in the ¹⁸F-fluorination reaction for the preparation of enantiomerically pure FET starting from (II).

Cite this article as:

Krasikova Raisa, Orlovskaya Victoria, Stepanova Maria and Fedorova Olga, The Effect of Reaction Media and Phase Transfer Catalyst on the Fluorination Yield and Enantiomeric Purity in Asymmetric Synthesis of O-(2'-[¹⁸F]fluoroethyl)-LTyrosine ([¹⁸F]FET), Current Organic Chemistry 2013; 17 (19) . https://dx.doi.org/10.2174/13852728113179990108