203398-44-1

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 37178-37-3 L-DOPA ethyl ester 
• 39740-30-2 ethyl (S)-2-amino-3-(3,4-dihydroxyphenyl)propanoate hydrochloride 
• 59-92-7 levodopa 

Downstream Products

• 1421282-51-0 N-(tert-butoxycarbonyl)-3,4-di(tert-butoxycarbonyloxy)-6-fluoro-L-phenylalanine ethyl ester 

Relevant academic research and scientific papers

6-[18F]Fluoro-L-DOPA by radiofluorodestannylation : A short and simple synthesis of a new labelling precursor

This paper describes a short and simple synthesis of a new fully protected stannylated precursor, namely N-(tert-butoxycarbonyl)-3,4-di(tert-butoxycarbonyloxy)-6-trimethylstannyl-L -phenylalanine ethyl ester, for the preparation of 6-[18F]fluoro-L-DOPA, used routinely in our Positron Emission Tomography program on neurodegenerative diseases as a tracer of the cerebral dopamine metabolism. The chemical pathway described for the total synthesis of our labelling precursor uses a straightforward protection sequence. This 4-step chemical synthesis allows the rapid preparation of several grammes of pure material in good overall yield. Regioselective radiofluorodestannylation using [18F]fluorine ([18F]F2, cyclotron-produced isotope, half-life : 110 min) gave pure 6-[18F]fluoro-L- DOPA (8) in good radiochemical yield (26% decay-corrected, based on starting [18F]fluorine recovered from the target) in 45-50 min after the End of Bombardment. The product was found to be >99% chemically, radiochemically and enantiomerically pure.

Convenient synthesis of diaryliodonium salts for the production of [18F]F-DOPA

[18F]F-DOPA is an important radiotracer that is used in the diagnosis of Parkinson's disease and neuroendocrine tumours. We describe a simple synthesis for a number of diaryliodonium salt precursors that are suitable for the production of [18F]F-DOPA through reaction with no carrier added (n.c.a.) nucleophilic [18F]fluoride. The simple procedure gives bench-stable, complex iodonium precursors in good yields without the need for laborious anhydrous conditions. Further alteration to the precursor counterion can be readily achieved for a range of halides and pseudo halides by a simple modification of the workup. Preliminary "hot" and "cold" fluorination results show the suitability of the compounds for the production of [18F]F-DOPA.

Fluorination of an arylboronic ester using [18F]selectfluor bis(triflate): Application to 6-[18F]fluoro-l-DOPA

The Ag-mediated electrophilic [18F]fluorination of an arylboronic ester is reported. This new radiochemical transformation uses [ 18F]selectfluor bis(triflate) in acetone. The process gave 6-[ 18F]fluoro-l-DOPA with a RCY of 19 ± 12% and a specific activity of 2.6 ± 0.3 GBq μmol-1.

NUCLEOPHILIC FLUORINATION OF AROMATIC COMPOUNDS

Iodylbenzene derivatives substituted with electron donating as well as electron withdrawing groups on the aromatic ring are used as precursors in aromatic nucleophilic substitution reactions. The iodyl group (IO2) is regiospecifically substituted by nucleophilic fluoride to provide the corresponding fluoroaryl derivatives. No-carrier-added [F-18] fluoride ion derived from anhydrous [F- 18]KF/Kryptofix, [F-18]CsF or a quaternary ammonium fluoride (e.g., Me4NF, Et4NF, n-Bu4NF, (PhCH2)4NF) exclusively substitutes the iodyl moiety in these derivatives and provides high specific activity F- 18 labeled fluoroaryl analogs. Iodyl derivatives of a benzothiazole analog and 6-iodyl-L-dopa derivatives have been synthesized as precursors and have been used in the preparation of no-carrier-added [F-18]fluorobenzothiazole as well as 6-[F-18]fluoro-L-dopa.

NO-CARRIER-ADDED NUCLEOPHILIC [F-18] FLUORINATION OF AROMATIC COMPOUNDS

Phenyliodonium ylide derivatives substituted with electron donating as well as electron withdrawing groups on the aromatic ring are shown for use as precursors in aromatic nucleophilic substitution reactions. The iodonium ylide group is substituted by nucleophiles such as halide ions to provide the corresponding haloaryl derivatives. No- carrier-added [F-18]fluoride ion exclusively substitutes the iodonium ylide moiety in these derivatives and provides high specific activity F- 18 labeled fluoro derivatives. Protected L-dopa-6-iodonium ylide derivative have been synthesized as a precursors for the preparation of no-carrier-added 6-[F- 18]fluoro-L-dopa. The iodonium ylide group in this L-dopa.derivative is nucleophilically substituted by no-carrier-added [F-18]fluoride ion to provide a [F-18]fluoro intermediates which upon acid hydrolysis yielded 6-[F- 18]fluoro-L-dopa.