{"title":"处理复杂问题","authors":"Francesco Zamberlan","doi":"10.1038/s41929-024-01244-y","DOIUrl":null,"url":null,"abstract":"<p>Now, as they report in <i>Chem</i>, Bortz, Bennett and Fasan leverage a cytochrome P450 site-selective C–H oxyfunctionalization as the key step to install functional groups as handles for directing chemical transformations of the scaffold, generating a library of complex small molecules, through a chemoenzymatic DOS (ceDOS) strategy.</p><p>The team used variants of fatty acid hydroxylase P450<sub>BM3</sub>, which were previously engineered for the regio- and stereoselective transformations of the sesquiterpene lactone parthenolide (PTL), a model target substrate that has anti-cancer and anti-inflammatory activity, into 9(S)-hydroxy-PTL, 14-hydroxy-PTL, and 1,10-epoxy-PTL. The stereoselectively installed functional groups were treated as chemical handles enabling diversity-generating transformations of PTL via, but not limited to, acid-catalysed rearrangements and (macro)cyclizations, ring-opening or -closing metathesis reactions, oxidations and esterifications, 1,4-additions and Diels–Alder cycloadditions on installed dienophiles. Overall, this structural diversification effort led to a library of 51 compounds. Chemoinformatic tools confirmed the elevated degree of diversity and complexity of the library, which encompasses a chemical space larger than that achievable with more common late-stage C–H functionalization strategies. Additionally, proof-of-principle assays showed a range of biological activities against cancer cell lines.</p>","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":null,"pages":null},"PeriodicalIF":42.8000,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Handles for complexity building\",\"authors\":\"Francesco Zamberlan\",\"doi\":\"10.1038/s41929-024-01244-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Now, as they report in <i>Chem</i>, Bortz, Bennett and Fasan leverage a cytochrome P450 site-selective C–H oxyfunctionalization as the key step to install functional groups as handles for directing chemical transformations of the scaffold, generating a library of complex small molecules, through a chemoenzymatic DOS (ceDOS) strategy.</p><p>The team used variants of fatty acid hydroxylase P450<sub>BM3</sub>, which were previously engineered for the regio- and stereoselective transformations of the sesquiterpene lactone parthenolide (PTL), a model target substrate that has anti-cancer and anti-inflammatory activity, into 9(S)-hydroxy-PTL, 14-hydroxy-PTL, and 1,10-epoxy-PTL. The stereoselectively installed functional groups were treated as chemical handles enabling diversity-generating transformations of PTL via, but not limited to, acid-catalysed rearrangements and (macro)cyclizations, ring-opening or -closing metathesis reactions, oxidations and esterifications, 1,4-additions and Diels–Alder cycloadditions on installed dienophiles. Overall, this structural diversification effort led to a library of 51 compounds. Chemoinformatic tools confirmed the elevated degree of diversity and complexity of the library, which encompasses a chemical space larger than that achievable with more common late-stage C–H functionalization strategies. Additionally, proof-of-principle assays showed a range of biological activities against cancer cell lines.</p>\",\"PeriodicalId\":18845,\"journal\":{\"name\":\"Nature Catalysis\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":42.8000,\"publicationDate\":\"2024-10-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature Catalysis\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.1038/s41929-024-01244-y\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, PHYSICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Catalysis","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1038/s41929-024-01244-y","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}
Now, as they report in Chem, Bortz, Bennett and Fasan leverage a cytochrome P450 site-selective C–H oxyfunctionalization as the key step to install functional groups as handles for directing chemical transformations of the scaffold, generating a library of complex small molecules, through a chemoenzymatic DOS (ceDOS) strategy.
The team used variants of fatty acid hydroxylase P450BM3, which were previously engineered for the regio- and stereoselective transformations of the sesquiterpene lactone parthenolide (PTL), a model target substrate that has anti-cancer and anti-inflammatory activity, into 9(S)-hydroxy-PTL, 14-hydroxy-PTL, and 1,10-epoxy-PTL. The stereoselectively installed functional groups were treated as chemical handles enabling diversity-generating transformations of PTL via, but not limited to, acid-catalysed rearrangements and (macro)cyclizations, ring-opening or -closing metathesis reactions, oxidations and esterifications, 1,4-additions and Diels–Alder cycloadditions on installed dienophiles. Overall, this structural diversification effort led to a library of 51 compounds. Chemoinformatic tools confirmed the elevated degree of diversity and complexity of the library, which encompasses a chemical space larger than that achievable with more common late-stage C–H functionalization strategies. Additionally, proof-of-principle assays showed a range of biological activities against cancer cell lines.
期刊介绍:
Nature Catalysis serves as a platform for researchers across chemistry and related fields, focusing on homogeneous catalysis, heterogeneous catalysis, and biocatalysts, encompassing both fundamental and applied studies. With a particular emphasis on advancing sustainable industries and processes, the journal provides comprehensive coverage of catalysis research, appealing to scientists, engineers, and researchers in academia and industry.
Maintaining the high standards of the Nature brand, Nature Catalysis boasts a dedicated team of professional editors, rigorous peer-review processes, and swift publication times, ensuring editorial independence and quality. The journal publishes work spanning heterogeneous catalysis, homogeneous catalysis, and biocatalysis, covering areas such as catalytic synthesis, mechanisms, characterization, computational studies, nanoparticle catalysis, electrocatalysis, photocatalysis, environmental catalysis, asymmetric catalysis, and various forms of organocatalysis.