Jun Yang, Brandon Singh, Gabriel Cohen and Chi P. Ting*,
{"title":"Chemoenzymatic Synthesis of 13-Oxoverruculogen","authors":"Jun Yang, Brandon Singh, Gabriel Cohen and Chi P. Ting*, ","doi":"10.1021/jacs.3c07078","DOIUrl":null,"url":null,"abstract":"<p >Verruculogens are rare fumitremorgin alkaloids that contain a highly unusual eight-membered endoperoxide. In this paper, we report a concise chemoenzymatic synthesis of 13-oxoverruculogen using enzymatic C–H peroxidation and rhodium-catalyzed C–C bond activation reactions to install the eight-membered endoperoxide and the pentacyclic core of the natural product, respectively. Our strategy involves the use of 13-<i>epi</i>-fumitremorgin B as a substrate analog for endoperoxidation by verruculogen synthase, FtmOx1. The resulting product, 13-<i>epi</i>-verruculogen, is the first unnatural endoperoxide generated by FtmOx1 and is used in the first synthesis of 13-oxoverruculogen. This strategy enables a 10-step synthesis of this natural product from commercially available starting materials and illustrates a hybrid approach utilizing biocatalytic and transition-metal-catalyzed reactions to access challenging alkaloid architectures. Moreover, this work demonstrates the use of native enzyme promiscuity as a viable strategy for the chemoenzymatic synthesis of natural products.</p>","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":14.4000,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the American Chemical Society","FirstCategoryId":"92","ListUrlMain":"https://pubs.acs.org/doi/10.1021/jacs.3c07078","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
Verruculogens are rare fumitremorgin alkaloids that contain a highly unusual eight-membered endoperoxide. In this paper, we report a concise chemoenzymatic synthesis of 13-oxoverruculogen using enzymatic C–H peroxidation and rhodium-catalyzed C–C bond activation reactions to install the eight-membered endoperoxide and the pentacyclic core of the natural product, respectively. Our strategy involves the use of 13-epi-fumitremorgin B as a substrate analog for endoperoxidation by verruculogen synthase, FtmOx1. The resulting product, 13-epi-verruculogen, is the first unnatural endoperoxide generated by FtmOx1 and is used in the first synthesis of 13-oxoverruculogen. This strategy enables a 10-step synthesis of this natural product from commercially available starting materials and illustrates a hybrid approach utilizing biocatalytic and transition-metal-catalyzed reactions to access challenging alkaloid architectures. Moreover, this work demonstrates the use of native enzyme promiscuity as a viable strategy for the chemoenzymatic synthesis of natural products.
期刊介绍:
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