Synthesis of Unsaturated Precursors for Parahydrogen-Induced Polarization and Molecular Imaging of 1-13C-Acetates and 1-13C-Pyruvates via Side Arm Hydrogenation.

Abstract

Hyperpolarized forms of 1-13C-acetates and 1-13C-pyruvates are used as diagnostic contrast agents for molecular imaging of many diseases and disorders. Here, we report the synthetic preparation of 1-13C isotopically enriched and pure from solvent acetates and pyruvates derivatized with unsaturated ester moiety. The reported unsaturated precursors can be employed for NMR hyperpolarization of 1-13C-acetates and 1-13C-pyruvates via parahydrogen-induced polarization (PHIP). In this PHIP variant, Side arm hydrogenation (SAH) of unsaturated ester moiety is followed by the polarization transfer from nascent parahydrogen protons to 13C nucleus via magnetic field cycling procedure to achieve hyperpolarization of 13C nuclear spins. This work reports the synthesis of PHIP-SAH precursors: vinyl 1-13C-acetate (55% yield), allyl 1-13C-acetate (70% yield), propargyl 1-13C-acetate (45% yield), allyl 1-13C-pyruvate (60% yield), and propargyl 1-13C-pyruvate (35% yield). Feasibility of PHIP-SAH 13C hyperpolarization was verified by 13C NMR spectroscopy: hyperpolarized allyl 1-13C-pyruvate was produced from propargyl 1-13C-pyruvate with 13C polarization of ∼3.2% in CD3OD and ∼0.7% in D2O. 13C magnetic resonance imaging is demonstrated with hyperpolarized 1-13C-pyruvate in aqueous medium.