Chemically modified nucleosi(ti)des and functional oligonucleotides (ONs, including therapeutic oligonucleotides, aptamer, nuclease, etc.) have been identified playing an essential role in the areas of medicinal chemistry, chemical biology, biotechnology, and nanotechnology. Introduction of functional groups into the nucleobases of ONs mostly relies on the laborious de novo chemical synthesis. Due to the importance of nucleosides modification and aforementioned limitations of functionalizing ONs, herein, we describe a highly efficient site-selective alkylation at the C8-position of guanines in guanosine (together with its analogues), GMP, GDP, and GTP, as well as late-stage functionalization of dinucleotides and single-strand ONs (including ssDNA and RNA) through photo-mediated Minisci reaction. Addition of catechol to assist the formation of alkyl radicals via in situ generated boronic acid catechol ester derivatives (BACED) markedly enhances the yields especially for the reaction of less stable primary alkyl radicals, and is the key to success for the post-synthetic alkylation of ONs. This method features excellent chemoselectivity, no necessity for pre-protection, wide range of substrate scope, various free radical precursors, and little strand lesion. Downstream applications in disease treatment and diagnosis, or as biochemical probes to study biological processes after linking with suitable fluorescent compounds are expected.

化学修饰的核苷和功能性寡核苷酸（ONs，包括治疗性寡核苷酸、适体、核酸酶等）已被确定在药物化学、化学生物学、生物技术和纳米技术领域发挥着重要作用。将官能团引入 ON 的核碱基中主要依赖于费力的从头化学合成。由于核苷修饰的重要性和上述功能化 ON 的限制，本文中，我们描述了鸟苷（及其类似物）、GMP、GDP 和 GTP 中鸟嘌呤 C8 位的高效位点选择性烷基化通过光介导的 Minisci 反应对二核苷酸和单链 ON（包括 ssDNA 和 RNA）进行后期功能化。通过原位生成的硼酸儿茶酚酯衍生物（BACED）添加儿茶酚来辅助烷基自由基的形成，显着提高了产率，特别是对于不太稳定的伯烷基自由基的反应，并且是合成后烷基化成功的关键ON。该方法具有化学选择性好、无需预保护、底物范围广、自由基前体多样、链损伤小等特点。预计在疾病治疗和诊断中的下游应用，或在与合适的荧光化合物连接后作为生化探针来研究生物过程。