578-12-1Relevant articles and documents
Synthesis of precursors for 18F-labeling of folic acid for PET application
Groehn, Viola,Moser, Rudolf,Ross, Tobias L.,Betzel, Thomas,Mueller, Cristina,Schibli, Roger,Ametamey, Simon
, p. 3639 - 3648 (2011/12/16)
Radiolabeled folate derivatives have the potential to target folate receptor-positive tumor cells for noninvasive diagnosis via positron emission tomography (PET) and single photon emission computed tomography (SPECT). We report the regiospecific synthesis of N2-(N,N-dimethylaminomethylene) -2′-nitrofolic acid di-tert-butyl ester (13) and N2-(N,N- dimethylaminomethylene)-N10-formyl-2′-nitrofolic acid dimethyl ester (25), which are precursors for the radiolabeling of folic acid with the PET isotope 18F. A modular synthetic strategy was applied: Fmoc- and Boc-protected 4-amino-2-nitrobenzoic acid were linked via amide bonds to di-tert-butyl l-glutamate and dimethyl l-glutamate, respectively, to form building blocks 10 and 19. After Fmoc and Boc removal, both compounds were coupled to 6-(bromomethyl)pterin hydrobromide to give crude 2′-nitrofolic acid di-tert-butyl ester and 2′-nitrofolic acid dimethyl ester. After formylation of 2′-nitrofolic acid dimethyl ester at N10 and the introduction of an N,N-dimethylaminomethylene group at N2, precursor 25 was obtained in an overall yield of 3%. The analogous 2′- fluoroderivative 28 was obtained in 7% overall yield from 4-amino-2- fluorobenzoic acid. Precursor 13 was obtained from 2′-nitrofolic acid di-tert-butyl ester in 6% yield after N2-protection. The synthesis of the reference materials 2′-nitro- and 2′-fluorofolic acid was achieved by the reaction of N-(4-amino-2-nitrobenzoyl)- and N-(4-amino-2- fluorobenzoyl)-l-glutamic acid with 6-(bromomethyl)pterin hydrobromide, giving 7% and 14% overall yield, respectively. Georg Thieme Verlag Stuttgart. New York.
