Semiconductor photocatalysis to engineering deuterated N-alkyl pharmaceuticals enabled by synergistic activation of water and alkanols
Zhaofei Zhang, Chuntian Qiu, Yangsen Xu, Qing Han, Junwang Tang, Kian Ping Loh, Chenliang Su
Abstract
Abstract Precisely controlled deuterium labeling at specific sites of N -alkyl drugs is crucial in drug-development as over 50% of the top-selling drugs contain N -alkyl groups, in which it is very challenging to selectively replace protons with deuterium atoms. With the goal of achieving controllable isotope-labeling in N -alkylated amines, we herein rationally design photocatalytic water-splitting to furnish [H] or [D] and isotope alkanol-oxidation by photoexcited electron-hole pairs on a polymeric semiconductor. The controlled installation of N -CH 3, -CDH 2, -CD 2 H, -CD 3 , and - 13 CH 3 groups into pharmaceutical amines thus has been demonstrated by tuning isotopic water and methanol. More than 50 examples with a wide range of functionalities are presented, demonstrating the universal applicability and mildness of this strategy. Gram-scale production has been realized, paving the way for the practical photosynthesis of pharmaceuticals.