Tyrosines, fluoro

Synthesis of fluorine-18 labelled fluoro-m-tyrosine, fluoro-m-tyramine and fluoro-3-hydroxyphenylacetic acid... 

A similar strategy, using a recently described PTC [158], was used to transform [2- F]fluoro-4-methoxy-benzylbromide into [2- F]fluoro-L-tyrosine (ee> 97%, 25% decay corrected, 100 min) (Scheme 26) [158b]. 

Figure 2 lists some other labelled compounds obtained by fluorodestannylation 4- and 6-p F]fluoro-/7 -tyramine [123], 2-[ F]fluoro-L-tyrosine [124], 2-[ F] oxoquazepam, an agonist of benzodiazepine receptors [125], 7-[ F]fluorota-crine, a potential agent for mapping acetylcholinesterase [126] and 2-[ F]fluoro-benzidine, a potential radioligand to image amyloid deposits in the brain [127]. 

The successful use of [ F]FDG in oncology PET imaging has prompted the design of several other radiopharmaceuticals, such as [ F]FLT ([ F]fluorothymi-dine, used as cellular proliferation marker. Scheme 36) [152-154], F-MISO ([ F] fluoromisonidazole, used to assess tissue hypoxia. Scheme 37) [155], c/s-4-[ F] fluoro-L-proline (used as abnormal collagen synthesis marker. Scheme 38) [156] and 0-(2-[ F]fluoroethyl)-L-tyrosine (used as amino acid transport and/or protein synthesis marker. Scheme 39) [157]. All these fluorine-18-labelled molecules have been prepared by aliphatic nucleophilic fluorination followed by a deprotection reaction. 

E. Hess, S. Sichler, A. Kluge, H.H. Coenen, Synthesis of 2-[18F]fluoro-L-tyrosine via regiospecific fluoro-de-stannylation, Appl. Radiat. Isot. 57 (2002) 185-191. 

Fluoro-ethyl-tyrosine (P F]- Radiolabeled amino Oncology... 

A strategy was developed to target such inhibitors to the CNS. (E)- S-Fluoro-methylene-m-tyrosine (26), the amino acid bioprecursor to 22f, was synthesized. The amino acid crosses the blood-brain barrier and is decarboxylated by... 

S.-C. Huang, J. Quintana, N. Satyamurthy, G. Lacan, D.-C. Yu, M.E. Phelps, J.R. Barrio, [ F]Fluoro- -fluoromethylene-m-tyrosine derivatives show stereo, geometrical, and regio specificities as in vivo central dopaminergic probes in monkeys, Nucl. Med. Biol. 26 (1999) 365-370. 

Fluorination of the aromatic ring (or in some cases also the introduction of the 18F isotope) in some bioactivc compounds has been successfully performed (e.g., fluoroantipyrine. fluoro-dopa).21 24,35 Regiospecific fluorination of the tyrosine ring of the A-terminal tetrapeptide amide (Tyr — n-Ala — Phe — Gly-NH2) sequence of the opiate peptide dermorphin was achieved in good yield by reaction with acetyl hypofluoritc to give 28.21... 

The very short reaction times required for the alkylation of substrate 11a with benzylic bromides using Nobin as an asymmetric phase-transfer catalyst are important for the synthesis of 18F-fluorinated amino adds for use in positron-emission tomography (PET)-imaging studies. Thus, Krasikova and Belokon have developed a synthesis of 2-[18F]fluoro-L-tyrosine and 6-[18F]fluoro-L-Dopa employing a (S)-Nobin-catalyzed asymmetric alkylation of glycine derivative 11a as the key step, as shown in Scheme 8.14 [29]. The entire synthesis (induding semi-preparative HPLC purification) could be completed in 110 to 120 min, which corresponds to one half-life of18 F. Both the chemical and enantiomeric purity of the final amino acids were found to be suitable for clinical use. 

The lipase-catalysed hydrolysis of methyl 2-fluoro-2-arylpropionates was proposed to proceed via a mechanism whereby, after ester hydrolysis, the enzyme facilitates the elimination of fluoride ion with the formation of a carbocation stabilized by the adjacent C02 group.230 Determination of the crystal structure of human sialidase Neu2, an enzyme that catalyses the hydrolysis of sialic acids, reveals a tyrosine residue that is positioned in the active site to stabilize the carbocation proposed as an intermediate in the hydrolysis.231 ll-Fluoro-all-frans-retinol is found to undergo isomerization to its 11 -cis form in the presence of visual cycle enzymes, in contrast to a previous study where no isomerization was reported.232 The result of the prior study was taken as evidence for a carbonium ion pathway in the isomerization. Although the authors of the present study do not rule out such a mechanism, they suggest that the isomerization mechanism remains unknown. Data obtained in a study of the oxidation of... 

The above iodides have been used as 1 -labelled building blocks in the preparations of [3-nC]tyrosine, (9-methyl[3-nC]tyrosine, /7-chloro[3-nC]phenylalanine and / -fluoro[3-JlC]phenylalanine by alkylations of glycine derivatives241. The [nC]ethyl ether derivatives (using sodium ethoxide as nucleophile) and 3-nitrophenyl-4-methoxy[(Z-nC]benzyl ether (using sodium 3-nitrophenolate) have been synthesized also, employing 4-methoxy(ar-14C)benzyl iodide 18324. ... 

The reaction was used to prepare many types of biologically interesting derivatives including fluoro hexestrol 29, fluoro tyrosine 30, various 4-fluorosteroidal enones 31, 6-fluorosteroids268, fluorobimans e.g. 32269 and fluorinated opiatic peptides 33, X = F, similar to dermorphin (equation 152)270. 

The compound l-fluoro-2,4-dinitrobenzene (FDNB) reacts with free amino, imidazole, and phenolic groups at neutral to alkaline pH to yield the corresponding, colored dinitrophenyl (DNP) compounds. Thus, FDNB will react with the free, unprotonated a-amino groups on amino acids, as well as with the side chains of lysine, histidine, and tyrosine (Fig. 6-1). Dansyl chloride is another compound that is known to react with the unprotonated, N-terminal amino groups of peptides. De-rivatization of peptides with this compound yields fluorescent products that provide a very sensitive method of detection of the amino acid derivatives (Fig. 6-2). 

Toyo oka T, Mantani T, Kato M. Reversible labeling of tyrosine residue in peptide using 4-fluoro-7-nitro-2,l,3-benzoxadiazole 131. and N-acetyl-L-cysteine. Analyt. Sci. 2003 19 341-346. 

To characterize protein-ligand interactions by F NMR, the ligand or the protein can be labeled with fluorine to produce spectra without overwhelming complexity. Proteins expressed in E.coli and tissue culture have been labeled with fluorine by biosynthetic incorporation of fluoro analogs of tryptophan, phenylalanine and tyrosine. Conformational properties of receptor... 

C11H12FN03 N-acetyl-2-fluoro-DL-phenylalanine 66574-84-3 25.00 1.2317 2 21998 C11H13N04 N-acetyl-L-tyrosine 537-55-3 22.50 1.1975 2... 

---