Asymmetric Synthesis of Carbon-11 Labelled α-Amino Acids for PET

For PET applications in oncological and neurological diagnostics, amino acids have been studied both clinically and pre-clinically during the last 35 years. Nowadays two applications of labelled amino acids for visualisation of tumours attract the main attention: [C-11] or [F-18]amino acids as substrates of specific membrane transport systems or in vivo measurement of protein synthesis rate. In this review we focussed on C-11-labelled amino acids, since synthetic approaches to [F-18]amino acids have been extensively reviewed in the literature. Most of optically pure C-11-labelled amino acids (except [C-11]methionine) have been prepared via low-yield non-reliable synthetic procedures. Low availability hampers their evaluation as biological probes. The first synthesis of racemic [C-11]lactic acid as an [C-11]amino acid precursor was published in 1941. It took more than thirty years to develop the first synthesis of a racemic [C-11]amino acid, it was published in 1973. Early examples of asymmetric synthesis of [C-11]amino acids led to relatively low enantiomeric excess, up to 82%. Amino acids synthons developed by groups led by Oppolzer, Seebach, Belokon and Horwell allowed highly stereospecific preparation of [C-11]amino acids. Enzymatic and biotechnological approaches, catalytic [C-11]alkylation of achiral glycine synthons or catalytic hydrogenation of [C-11]precursors have not resulted in any practically useful syntheses yet. The importance for PET using new substituted amino acids is briefly discussed.