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.

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 CD3 OD and ∼0.7% in D2 O. 13 C magnetic resonance imaging is demonstrated with hyperpolarized 1-13 C-pyruvate in aqueous medium.