Nirmatrelvir is an inhibitor of the SARS-CoV-2 main protease and is the active ingredient in Paxlovid. Nirmatrelvir presents a significant synthetic challenge, in no small part due to a cost-driving lactam-containing fragment with two stereogenic centers. Our goal was to help decrease the cost of nirmatrelvir by developing a scalable low-cost synthesis of this fragment, avoiding the use of cryogenic conditions reported in the initial route. Herein, we disclose three catalytic asymmetric routes toward this fragment, via (i) chiral Lewis acid (copper) catalysis, (ii) chiral Bro̷nsted base organocatalysis, and (iii) chiral bifunctional hydrogen-bond-donor organocatalysis.

中文翻译：

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开发新的催化不对称路线以实现 Nirmatrelvir 的成本驱动构件


Nirmatrelvir 是 SARS-CoV-2 主要蛋白酶的抑制剂，也是 Paxlovid 的活性成分。 Nirmatrelvir 提出了重大的合成挑战，这在很大程度上是由于具有两个立体中心的含内酰胺片段的成本驱动。我们的目标是通过开发该片段的可扩展低成本合成方法来帮助降低 nirmatrelvir 的成本，避免使用初始路线中报道的低温条件。在此，我们公开了该片段的三种不对称催化途径，通过（i）手性路易斯酸（铜）催化，（ii）手性布朗斯台德碱有机催化，和（iii）手性双功能氢键供体有机催化。