Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical Sciences, Chongqing University, 401331 Chongqing, P. R. China.
Pharmaceutical Department of Chongqing Three Gorges Central Hospital, Chongqing University Three Gorges Hospital, 404100 Chongqing, P. R. China.
Org Biomol Chem. 2023 Mar 8;21(10):2162-2166. doi: 10.1039/d2ob02278h.
Viridicatin alkaloids as natural products have attracted great interest due to their unique core scaffold. To fully exploit their potential application in DNA-encoded chemical libraries that would facilitate drug discovery, we here describe an efficient on-DNA synthesis of viridicatin alkaloid-like scaffolds from isatins and DNA-tagged aldehydes. Promoted by benzenesulfonyl hydrazide, this reaction provided the corresponding DNA-conjugated viridicatin alkaloid-like products in moderate-to-excellent conversion yields, and DNA compatibility validated by enzymatic ligation and qPCR evaluation exhibited the feasible utility of this methodology in DEL synthesis. Cross substrate scope study, together with subsequent on-DNA chemical diversification, further showed the competence of this approach in focused natural product-like encoded library construction.
由于其独特的核心支架，作为天然产物的变色烯生物碱引起了极大的兴趣。为了充分利用它们在 DNA 编码化学文库中的潜在应用，从而促进药物发现，我们在这里描述了一种从色酮和 DNA 标记醛高效合成类似于变色烯生物碱支架的方法。在苯磺酰肼的促进下，该反应以中等至优异的转化率提供了相应的 DNA 连接的类似于变色烯生物碱的产物，通过酶连接和 qPCR 评估验证的 DNA 相容性表明了该方法在 DEL 合成中的可行用途。交叉底物范围研究，以及随后的 DNA 化学多样化，进一步表明了该方法在聚焦于天然产物样编码文库构建中的能力。
