Fluoroalanine, specifically 3-fluoro-alanine, is a fluorinated analogue of the amino acid alanine. Historically considered as an antibiotic, it also has potential applications as a radioactive tracer in positron emission tomography (PET).
The first reported syntheses of fluoroalanine in 1976 involved treating cysteine with difluorine under an inert atmosphere. This produced a mixture of 3-fluoroalanine and 3,3-difluoroalanine, with the former as the major component.
3-Fluoroalanine, 3,3-difluoroalanine, and 3,3,3-trifluoroalanine can also be synthesised by treating alanine directly with UV-irradiated trifluoromethyl hypofluorite.
Optically pure 3-fluoroalanines can be produced through an oxazolidinone intermediate that can be obtained from L- or D-serine. Enzymatic synthesis of alanine with varying degrees of fluorination has been reported, using substrates such as 3-fluoropyruvate and a serine-derivatised sulfamidate.
3-Fluoroalanine produced using the radioactive <sup>18</sup>F isotope has potential applications in Positron Emission Tomography as a radioactive tracer. The D-enantiomer has shown promise in differentiating between bacterial infection and sterile inflammation. A deuterated L-enantiomer expressed enhanced tumour uptake, warranting further biological investigation into its use as a cancer imaging agent.
3-Fluoroalanine is described as unstable and generally unsuitable for peptide synthesis. Under basic conditions, it is prone to dehydrofluorination, and the proximity of the fluorine substituent to the amine group reduces the nucleophilicity of the latter. However, it has been successfully used in developing analogues to the immunosuppressant Cyclosporin A. Additionally, dehydrofluorination of 3-fluoroalanine produces a double-bond, providing a route for further amino acid functionalisation. In 2015, the synthesis of N-Fmoc-protected 3-fluoroalanine grants viable routes towards incorporating fluorinated alanine probes within synthetic peptides.
While fluoroalanine may refer to various isomers of 3-fluoroalanine, other functional analogues and isotopologues are of note.