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

[Image: see text] Hyperpolarized forms of 1-(13)C-acetates and 1-(13)C-pyruvates are used as diagnostic contrast agents for molecular imaging of many diseases and disorders. Here, we report the synthetic preparation of 1-(13)C 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-(13)C-acetates and 1-(13)C-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 (13)C nucleus via magnetic field cycling procedure to achieve hyperpolarization of (13)C nuclear spins. This work reports the synthesis of PHIP-SAH precursors: vinyl 1-(13)C-acetate (55% yield), allyl 1-(13)C-acetate (70% yield), propargyl 1-(13)C-acetate (45% yield), allyl 1-(13)C-pyruvate (60% yield), and propargyl 1-(13)C-pyruvate (35% yield). Feasibility of PHIP-SAH (13)C hyperpolarization was verified by (13)C NMR spectroscopy: hyperpolarized allyl 1-(13)C-pyruvate was produced from propargyl 1-(13)C-pyruvate with (13)C polarization of ∼3.2% in CD(3)OD and ∼0.7% in D(2)O. (13)C magnetic resonance imaging is demonstrated with hyperpolarized 1-(13)C-pyruvate in aqueous medium.