氰基胍环化方法构建瑞德西韦的碱基。

Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095-1569, United States.

Department of Chemistry, University of California, Berkeley, California 94720, United States.

Org Lett. 2020 Nov 6;22(21):8430-8435. doi: 10.1021/acs.orglett.0c03052. Epub 2020 Oct 21.

We report an alternative approach to the unnatural nucleobase fragment seen in remdesivir (Veklury). Remdesivir displays broad-spectrum antiviral activity and is currently being evaluated in Phase III clinical trials to treat patients with COVID-19. Our route relies on the formation of a cyanoamidine intermediate, which undergoes Lewis acid-mediated cyclization to yield the desired nucleobase. The approach is strategically distinct from prior routes and could further enable the synthesis of remdesivir and other small-molecule therapeutics.

我们报告了瑞德西韦（Veklury）中所见到的非天然核苷片段的另一种方法。瑞德西韦具有广谱抗病毒活性，目前正在进行 III 期临床试验，以治疗 COVID-19 患者。我们的路线依赖于氰基脒中间体的形成，该中间体经路易斯酸介导的环化反应生成所需的核苷。该方法在策略上与先前的路线不同，可能进一步促进瑞德西韦和其他小分子治疗药物的合成。