Expanding DNA functionality has significant implications in nucleic acid chemistry, biology, and beyond. Therefore, developing new chemical tools for site-specific post-synthetic modification of nucleic acids is urgently needed. Herein, we demonstrate the first site-specific DNA post-synthetic modification via visible-light-catalyzed decarboxylative allylation. Allyl sulfone groups were introduced into DNA, not only at the terminal sites via amide formation but also at internal and terminal positions during DNA solid-phase synthesis. This visible-light-catalyzed decarboxylative allylation proceeds rapidly on DNA bearing allyl sulfone groups under open-air conditions within minutes, exhibiting excellent chemoselectivity and compatibility with various functional groups while retaining DNA integrity. Specifically, introducing allyl sulfones into DNA via solid-phase synthesis enables site-specific modification on chemically synthesized single-stranded DNA (internal and terminal positions), hybridized double-stranded DNA, and enzymatically amplified long-chain DNA under visible light irradiation. The versatile reactivity of allyl sulfone scaffolds further enables diverse on-DNA photocatalytic transformations, promising to advance the chemical toolbox for DNA post-synthetic modification through diverse photochemical methods.

中文翻译：

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通过快速光催化烯丙基化进行位点特异性 DNA 合成后修饰


扩展 DNA 功能对核酸化学、生物学等领域具有重大影响。因此，迫切需要开发新的化学工具来对核酸进行位点特异性合成后修饰。在此，我们通过可见光催化脱羧烯丙基化展示了第一个位点特异性 DNA 合成后修饰。烯丙基砜基团不仅通过酰胺形成在末端位点引入到 DNA 中，而且还在 DNA 固相合成过程中引入到内部和末端位置。这种可见光催化的脱羧烯丙基化反应在露天条件下在几分钟内在带有烯丙基砜基团的 DNA 上快速进行，表现出优异的化学选择性和与各种官能团的相容性，同时保持 DNA 完整性。具体来说，通过固相合成将烯丙基砜引入DNA中，可以在可见光照射下对化学合成的单链DNA（内部和末端位置）、杂交的双链DNA和酶促扩增的长链DNA进行位点特异性修饰。烯丙基砜支架的多功能反应性进一步实现了多种DNA上光催化转化，有望通过多种光化学方法推进DNA合成后修饰的化学工具箱。