Synthesis of Isotopically Modified Derivatives of Dopamine, Serotonin, and Doxorubicin with Boc-Pro and Boc-[2H]Pro

Abstract

Boc-Pro-Dox, Boc-Pro-DOPA, Boc-Pro-Srt, and Pro-Dox, Pro-DOPA, Pro-Srt, as well as Boc-[²Н]Pro-Dox, Boc-[²Н]Pro-DOPA, Boc-[²Н]Pro-Srt, and [²Н]Pro-Dox, [²Н]Pro-DOPA, [²Н]Pro-Srt have been synthesized for the first time. Boc-[²Н]Pro is the most promising reagent for the preparation of deuterated compounds. The hydrogenation of Boc-ΔPro in ethyl acetate on palladium catalyst has allowed the introduction of deuterium by a factor of 1.6–1.65 larger than by the hydrogenation of unsaturated proline bound to serotonin and by a factor of three larger than by the hydrogenation of unsaturated proline bound to dopamine. Due to doxorubicin instability under conditions of unsaturated proline hydrogenation, its condensation with Boc-[²Н]Pro is the sole possibility to prepare Boc-[²Н]Pro-Dox. The content of isotopomers in the deuterated products has been determined by mass spectrometry.