Abstract：
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).
摘要：
我们在此提出了一种新型的光介导的均裂C-S键形成，用于制备烷基硫嘌呤和烷基硫嘌呤核苷。尽管存在Minisci反应的反应位点，化学选择性S-烷基化仍然是主要途径。这种方法可以在后期将广谱的烷基引入到未保护的巯基嘌呤衍生物的硫原子上，包括2-，6-，和8-巯基嘌呤环。有机硼可用作高效且环保的烷基化试剂，在容易获得方面提供优势，稳定性,减少毒性。硫醚化核苷的进一步衍生化，与抗肿瘤试验一起，导致发现了有效的抗肿瘤剂，其IC50值达到6.1µM（比较。31代表Jurkat）。
