Synthesis and hyperpolarization of 13C and 2H labeled vinyl pyruvate and pyruvate

Abstract

The hyperpolarization of nuclear spins has enabled unique applications in chemistry, biophysics, and particularly in metabolic imaging. Parahydrogen-induced polarization (PHIP) offers a fast and cost-efficient way of hyperpolarization. Nevertheless, PHIP lags behind dynamic nuclear polarization (DNP), which is already being evaluated in clinical studies. This shortcoming is mainly due to problems in the synthesis of the corresponding PHIP precursor molecules. The most widely used DNP tracer in clinical studies, particularly for the detection of prostate cancer, is 1-13C-pyruvate. The ideal derivative for PHIP is the deuterated vinyl ester because the spin physics allows for 100% polarization. Unfortunately, there is no efficient synthesis for vinyl esters of -ketocarboxylic acids in general and pyruvate in particular. Here, we present an efficient new method for the preparation of vinyl esters, including 13C labeled, fully deuterated vinyl pyruvate using a palladium catalyzed procedure. Using 50 % enriched parahydrogen and mild reaction conditions, a 13C polarization of 12% was readily achieved; 36% are expected with 100% pH2. Higher polarization values can be potentially achieved with optimized reaction conditions.