分子の原子1個を置換する新手法で創薬を高速化（New method swaps single atom in a molecule to speed drug discovery） 記事の日付と機関名：2026-08-31 シカゴ大学（UChicago）

2026-08-31 シカゴ大学（UChicago）

＜関連情報＞

• https://news.uchicago.edu/story/new-method-swaps-single-atom-molecule-speed-drug-discovery
• https://www.nature.com/articles/s41586-026-10933-6

イソオキサゾールからのピロールの合成（O-C骨格編集による） Synthesis of pyrroles from isoxazoles by an O-to-C skeletal edit

Abigail J. Bracken,Alexandra P. Lawrie,Isabella F. Romita & Mark D. Levin
Nature  Published:19 August 2026
DOI:https://doi.org/10.1038/s41586-026-10933-6

Abstract

Isoxazoles and pyrroles feature prominently in pharmaceutical and bioactive compounds of interest^1,2. Although their core structures differ by only a single atom (O versus C), their respective de novo ring assemblies require vastly different syntheses, as the electronically consonant isoxazole core is amenable to a range of disconnections that are inaccessible for the corresponding pyrroles^3,4. Given the structural similarity between these two heterocyclic classes, skeletal editing offers an opportunity to meet this need, as it empowers non-traditional retrosynthetic disconnections⁵. Here we achieve an O-to-C atom replacement of isoxazoles, affording pyrroles in a one-pot sequence. We identify the N-propargylic enaminone as a key intermediate connecting the two heterocycle classes, providing a retrosynthetic disconnection orthogonal to traditional syntheses for otherwise challenging pyrrole scaffolds⁶. During our investigations, we encountered unexpected enaminone reactivity and developed a predictive computational model capturing the conformational features controlling reaction outcomes⁷. Regioselective syntheses of elusive pyrroles can be achieved by linking these two heterocycles with an O-to-C replacement reaction.