Diastereoselectively labeled (3S)-[4-13C]-L-valine and regioselectively labeled [3-Â3CH3]-L-isoleucine hydrochlorides were synthesized in 54% and 62% respective overall yields from L-aspartic acid.
Carbon-13 labeled amino acids and their derivatives are important probes for the study of biochemical systems due to their enhanced spectroscopic detectability. In addition to acting as tracers for the elucidation of various metabolic pathways ]-s with the aid of 13C NMR 9 and/or infrared spectroscopy, 1° they are useful for NMR structural studies of proteins.t ht 2 This approach requh'es the complete assignment of 1H resonances, a task that is complicated by chemical shift overlap and consequently requires multi-dimensional heteronuclear NMR. ]316 Many of these methods rely on IH-13C or 13C-13C correlation, and often necessitate regio-and/or stereoselective isotopic enrichment, tS,17-t9 Other NMR techniques, such as Rotational Resonance, 2°-25 can provide structural information even for non-crystalline or insoluble proteins, but they also require selective isotopic enrichment. 26-3° This selective enrichment is generally accomplished by the judicious incorporation of synthetically or biosynthetically 31 derived, carbon-13 labeled amino acids. In light of the importance of such probes, we wish to report efficient syntheses of diastereoselectively labeled [13C]-L-valine and regioselectively labeled [13C]-L-isoleucine hydrochlorides 7 and 16 in 54% and 62% respective overall yields from L-aspartic acid. 33
Scheme 1
Bnl~l--CO2CH3 2. 1~;H31