Fluoro-L-proline

This solid phase radiofluorination was also shown efficient for the stereospecific and semi-automated preparation of cis- and fran5-[4- F]fluoro-L-proline, markers of the collagen synthesis [1091 (Scheme 52). 

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. 

K. Hamacher, Synthesis of n.c.a. cis- and trans-4-[ F]fluoro-L-proline, radiotracers for PET-investigation of disordered matrix protein synthesis, J. Label. Compds Radiopharm. 42 (1999) 1135-1144. 

FJFluoroproUne in Positron Emission Tomography There have been several reports of the synthesis of [ F]4-fluoro-L-proline. The first synthesis reported in 1983 involved reaction of tetraethylammonium [ FJfluoride with 4-A -tosly-4-trifluoromethanesulfonyloxy-L-proline methyl ester " (Fig. 3.17). Hamacher and coworkers reported the syntheses of no-carrier-added (NCA) cis-and tra 5 -[ F]4-fluoro-L-prolines by Kryptohx 222-mediated nucleophilic [ F] fluorination of cis- and trans- A-t-Boc-4-tosyloxy-L-prolines followed by... 

Gottlieb, A.A. Fujita, Y Undenfriend, S. Witkop, B. Incorporation of cis- and trans-4-fluoro-L-prolines and hydroxylation of the trans isomer during collagen biosynthesis. Biochemistry 1965, 4, 2507-2513. 

Mazza, S.M. Stereospecific, semi-automated, N.C.A. syntheses of cA-4-[ F]fluoro-L-proline and fra 5-4-[ F]fluoro-L-proline. /. Label. Compd. Radiopharm. 2000, 43, 1047-1058. 

Wallace WE, Gupta NC, Hubbs AF, Mazza SM, Bishop HA, Keane MJ, BatteUi LA, Ma J, Schleiff P. Cw-4-[ F]Fluoro-L-Proline PET imaging of pulmonary fibrosis in a rabbit model. J Nucl Med 2002 43 413-420. 

Gerig JT, McLeod RS (1973) Conformation of cis- and /raini-4-fluoro-L-proline in aqueous solution. J Am Chem Soc 95 5725-5729... 

Effective pathway towards 3-fluoropyrrole 37 was elaborated on the base of easily available methyl tranv-4-hydroxy-L-prolinate 32. After Boc-protection of this compound followed by oxidation with PDC, ketone obtained 34, was converted into difluoride 35 by the reaction with DAST. N-Boc deprotection of 35 with trifluoroacetic acid afforded, after basic treatment, free base 36 which was aromatized by activated manganese dioxide into methyl 4-fluoro-lH-pyrrole-2-carboxylate 37 [15, 19],... 

A simple and rapid method of separating optical isomers of amino acids on a reversed-phase plate, without using impregnated plates or a chiral mobile phase, was described by Nagata et al. [27]. Amino acids were derivatized with /-fluoro-2,4-dinitrophenyl-5-L-alanine amide (FDAA or Marfey s reagent). Each FDAA amino acid can be separated from the others by two-dimensional elution. Separation of L- and D-serine was achieved with 30% of acetonitrile solvent. The enantiomers of threonine, proline, and alanine were separated with 35% of acetonitrile solvent and those of methionine, valine, phenylalanine, and leucine with 40% of acetonitrile solvent. The spots were scraped off the plate after the... 

It has been described the reaction between acetone (13.6 equiv.) with a-fluoro and a,a-difluoro (l-keto esters catalyzed by (5)-proline (20 mol%) in DMSO at 25°C [67], with good yield (87%), low diastereoselectivity (11% de) and high enantiose-lectivity (81%) being obtained in the reaction of ethyl 2-fluoroacetoacetonate. 

Since intramolecular transannular aldol reactions create two new rings and at least two new stereogenic centers in a single process, the corresponding cyclic p-hydroxy ketones are useful for the synthesis of polycyclic natural products. The trons-4-fluoro proline 48 is superior to (S)-proline in catalysis of this type of reaction, affording excellent diastereoselectivity and enantioselectivity (Scheme 28.4). The utility of this reaction has been demonstrated in a total synthesis of (-l-)-hirustene (50), is a fungal metabolite first isolated from the basidiomycete Coriolus consors [27]. 

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