A Precursor for Electrochemical radiosynthesis of [¹⁸F]-L-DOP

Objectives [¹⁸F]-L-DOPA (1 in Scheme 1) is a useful PET tracer for imaging of neuropsychiatric diseases, movement disorders, and brain malignancies. However, the widely used method to prepare the [¹⁸F]-L-DOPA depends on carrier-added introduction of ¹⁸F, which leads to low radiochemical yield and specific activity^[1]. To tackle this problem, we herein explore a method to synthesize [¹⁸F]-L-DOPA via electrochemical fluorination.

Methods Our group has developed a method to introduce ¹⁸F by electrochemical fluorination, in which t-Butyl group on aromatic ring can be activated and replaced by ¹⁸F fluoride^{[2, 3]}. The multistep synthesis of the t-Butyl containing precursor molecule for L-DOPA 2 is outlined here.

Results We have explored two methods to attach t-Butyl group on the aromatic ring of L-Dopa. The most direct approach was to introduce t-Butyl onto L-DOPA 3. Unfortunately this approach resulted in the 5-t-Butyl-isomer 4 as the only detected t-butylated product. The electrofluorinationof 5, with t-Butyl as the leaving group, afforded F-labeled compound. The second method we are exploring is to start with the 5-t-Butyl containing synthesis block 6, together with 7, to construct the precursor 2^[3].

Conclusions The fluorination of precursor 5 by our electronchemical method provided a proof of concept for our strategy to synthesize 1 from 2. We had also demonstrated that t-Butyl in 4-t-butyl-diBoc-catechol, can be replaced by ¹⁸F under carrier free condition^[3] with a radiochemical yield of 6.8±1.3%, and achieved a specific activity of 13 GBq/µmol. Therefore precursor 2 is expected to be converted to the desired 1 by no-carrier-added electrochemical radiofluorination^[3], followed by deprotection.