New catalytic strategies for one-pot total synthesis of L-carnosine

The global market of L-Carnosine is experiencing a steady growth driven by its spreading applications in nutrition, therapeutics, and cosmetics. L-Carnosine, a dipeptide composed of β-alanine and L-histidine plays key roles in oxidative stress reduction and energy metabolism with a therapeutic potential extending to conditions like diabetes, Alzheimer’s, and Parkinson’s diseases. In an attempt to develop a more sustainable synthetic pathway able to afford L-Carnosine in satisfactory yield and enantiopurity, we set up a one-pot protocol starting from compound 14, ethyl methyl (Z)-2-(2-cyanoacetamido)-3-(1H-imidazol-4-yl)acrylate, synthesized as a Privileged Precursor (PP) of L-Carnosine. The asymmetric reduction of the C=C bond in PP with [RhCOD(R,R)-Ephos]+TfO-, followed by the hydrogenation of the CN moiety using a Rh/C heterogeneous catalyst under basic conditions, afforded the desired product with an overall 68% yield and up to 73% e.e. as confirmed by HPLC-MS analysis. Although the developed protocol reduces synthetic and purification steps, further optimization is still ongoing to enable industrial application.