%0 Journal Article
%T Visible Light-Mediated Late-Stage Thioetherification of Mercaptopurine Derivatives.
%A Ge Y
%A Peng Y
%A Xie R
%A Luo Y
%A Li Y
%A Chen G
%J Chemistry
%V 0
%N 0
%D 2024 Jun 26
%M 38923704
%F 5.02
%R 10.1002/chem.202401774
%X We disclose herein a novel and general radical approach to alkylthiopurines, encompassing 4 types of thiopurines, as well as their corresponding ribosides. This strategy is achieved through visible light-mediated late-stage functionalization of the sulfur atoms of mercaptopurines. The in situ-generated disulfide was proposed as the pivotal neutral intermediate for this transformation. We present herein a novel photo-mediated homolytic C-S bond formation for the preparation of alkylthiopurines and alkylthiopurine nucleosides. Despite the presence of reactive sites for the Minisci reaction, chemoselective S-alkylation remained the predominant pathway. This method allows for the late-stage introduction of a broad spectrum of alkyl groups onto the sulfur atom of unprotective mercaptopurine derivatives, encompassing 2-, 6-, and 8-mercaptopurine rings. Organoborons serve as efficient and eco-friendly alkylating reagents, providing advantages in terms of readily availability, stability, and reduced toxicity. Further derivatization of the thioetherified nucleosides, together with anti-tumor assays, led to the discovery of potent anti-tumor agents with an IC50 value reaching 6.1 μM (Comp. 31 for Jurkat).