{"title":"A comprehensive understanding of the mechanism of the biomimetic total synthesis of brevianamide A†","authors":"Wenqiang Xu, Tian-Yu Sun, Yingtong Di, Xiaojiang Hao and Yun-Dong Wu","doi":"10.1039/D4OB00915K","DOIUrl":null,"url":null,"abstract":"<p >Recently, several studies on the chemical synthesis of brevianamide A (<strong>BA</strong>) were reported. In particular, a highly efficient and remarkably selective synthetic strategy was reported by Lawrence's group. However, a unified mechanistic understanding of these results is still lacking. We have carried out a DFT study and proposed a unified mechanism to understand these experimental results. Starting from intermediate <strong>2</strong>, the most favorable reaction sequence is a fast tautomerization, followed by a σ-migration of the base moiety, and a final inverse-electron demanding Diels–Alder reaction, resulting in the formation of the <strong>BA</strong> product stereoselectively. This reaction mechanism can also be applied to understand the biosynthesis of <strong>BA</strong> that involves enzymatic catalysis.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Bio Materials","FirstCategoryId":"92","ListUrlMain":"https://pubs.rsc.org/en/content/articlelanding/2024/ob/d4ob00915k","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
引用次数: 0
Abstract
Recently, several studies on the chemical synthesis of brevianamide A (BA) were reported. In particular, a highly efficient and remarkably selective synthetic strategy was reported by Lawrence's group. However, a unified mechanistic understanding of these results is still lacking. We have carried out a DFT study and proposed a unified mechanism to understand these experimental results. Starting from intermediate 2, the most favorable reaction sequence is a fast tautomerization, followed by a σ-migration of the base moiety, and a final inverse-electron demanding Diels–Alder reaction, resulting in the formation of the BA product stereoselectively. This reaction mechanism can also be applied to understand the biosynthesis of BA that involves enzymatic catalysis.