IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-49629-8.html
   My bibliography  Save this article

Asymmetric total synthesis of polycyclic xanthenes and discovery of a WalK activator active against MRSA

Author

Listed:
  • Min-Jing Cheng

    (Jinan University
    Jinan University)

  • Yan-Yi Wu

    (Jinan University
    Jinan University)

  • Hao Zeng

    (Army Medical University)

  • Tian-Hong Zhang

    (Jinan University
    Jinan University)

  • Yan-Xia Hu

    (Jinan University
    Jinan University)

  • Shi-Yi Liu

    (Southern University of Science and Technology))

  • Rui-Qin Cui

    (Southern University of Science and Technology))

  • Chun-Xia Hu

    (Southern University of Science and Technology))

  • Quan-Ming Zou

    (Army Medical University)

  • Chuang-Chuang Li

    (Southern University of Science and Technology)

  • Wen-Cai Ye

    (Jinan University
    Jinan University)

  • Wei Huang

    (Southern University of Science and Technology))

  • Lei Wang

    (Jinan University
    Jinan University)

Abstract

The development of new antibiotics continues to pose challenges, particularly considering the growing threat of multidrug-resistant Staphylococcus aureus. Structurally diverse natural products provide a promising source of antibiotics. Herein, we outline a concise approach for the collective asymmetric total synthesis of polycyclic xanthene myrtucommulone D and five related congeners. The strategy involves rapid assembly of the challenging benzopyrano[2,3-a]xanthene core, highly diastereoselective establishment of three contiguous stereocenters through a retro-hemiketalization/double Michael cascade reaction, and a Mitsunobu-mediated chiral resolution approach with high optical purity and broad substrate scope. Quantum mechanical calculations provide insight into stereoselective construction mechanism of the three contiguous stereocenters. Additionally, this work leads to the discovery of an antibacterial agent against both drug-sensitive and drug-resistant S. aureus. This compound operates through a unique mechanism that promotes bacterial autolysis by activating the two-component sensory histidine kinase WalK. Our research holds potential for future antibacterial drug development.

Suggested Citation

  • Min-Jing Cheng & Yan-Yi Wu & Hao Zeng & Tian-Hong Zhang & Yan-Xia Hu & Shi-Yi Liu & Rui-Qin Cui & Chun-Xia Hu & Quan-Ming Zou & Chuang-Chuang Li & Wen-Cai Ye & Wei Huang & Lei Wang, 2024. "Asymmetric total synthesis of polycyclic xanthenes and discovery of a WalK activator active against MRSA," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49629-8
    DOI: 10.1038/s41467-024-49629-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-49629-8
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-49629-8?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Shuhei Kawamura & Hang Chu & Jakob Felding & Phil S. Baran, 2016. "Nineteen-step total synthesis of (+)-phorbol," Nature, Nature, vol. 532(7597), pages 90-93, April.
    2. Kyle W. Quasdorf & Larry E. Overman, 2014. "Catalytic enantioselective synthesis of quaternary carbon stereocentres," Nature, Nature, vol. 516(7530), pages 181-191, December.
    3. Zongqiang Wang & Bimal Koirala & Yozen Hernandez & Matthew Zimmerman & Steven Park & David S. Perlin & Sean F. Brady, 2022. "A naturally inspired antibiotic to target multidrug-resistant pathogens," Nature, Nature, vol. 601(7894), pages 606-611, January.
    4. Elizabeth J. Culp & Nicholas Waglechner & Wenliang Wang & Aline A. Fiebig-Comyn & Yen-Pang Hsu & Kalinka Koteva & David Sychantha & Brian K. Coombes & Michael S. Nieuwenhze & Yves V. Brun & Gerard D. , 2020. "Evolution-guided discovery of antibiotics that inhibit peptidoglycan remodelling," Nature, Nature, vol. 578(7796), pages 582-587, February.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Christopher J. Barden & Fan Wu & J. Pedro Fernandez-Murray & Erhu Lu & Shengguo Sun & Marcia M. Taylor & Annette L. Rushton & Jason Williams & Mahtab Tavasoli & Autumn Meek & Alla Siva Reddy & Lisa M., 2024. "Computer-aided drug design to generate a unique antibiotic family," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    2. Po-Kai Peng & Andrew Isho & Jeremy A. May, 2024. "Regio- and enantioselective synthesis of acyclic quaternary carbons via organocatalytic addition of organoborates to (Z)-Enediketones," Nature Communications, Nature, vol. 15(1), pages 1-9, December.
    3. Xueqin Shu & Yingying Shi & Yi Huang & Dan Yu & Baolin Sun, 2023. "Transcription tuned by S-nitrosylation underlies a mechanism for Staphylococcus aureus to circumvent vancomycin killing," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Bin Ma & Caiyu Lu & Yiling Wang & Jingwen Yu & Kankan Zhao & Ran Xue & Hao Ren & Xiaofei Lv & Ronghui Pan & Jiabao Zhang & Yongguan Zhu & Jianming Xu, 2023. "A genomic catalogue of soil microbiomes boosts mining of biodiversity and genetic resources," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    5. Zongbin Jia & Liang Cheng & Long Zhang & Sanzhong Luo, 2024. "Asymmetric C–H Dehydrogenative Alkenylation via a Photo-induced Chiral α‑Imino Radical Intermediate," Nature Communications, Nature, vol. 15(1), pages 1-8, December.
    6. Laura Nies & Susheel Bhanu Busi & Mina Tsenkova & Rashi Halder & Elisabeth Letellier & Paul Wilmes, 2022. "Evolution of the murine gut resistome following broad-spectrum antibiotic treatment," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    7. Ming-Ming Li & Tianze Zhang & Lei Cheng & Wei-Guo Xiao & Jin-Tao Ma & Li-Jun Xiao & Qi-Lin Zhou, 2023. "Ketone α-alkylation at the more-hindered site," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    8. Mathias H. Hansen & Martina Adamek & Dumitrita Iftime & Daniel Petras & Frauke Schuseil & Stephanie Grond & Evi Stegmann & Max J. Cryle & Nadine Ziemert, 2023. "Resurrecting ancestral antibiotics: unveiling the origins of modern lipid II targeting glycopeptides," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    9. Zhuo Cheng & Bei-Bei He & Kangfan Lei & Ying Gao & Yuqi Shi & Zheng Zhong & Hongyan Liu & Runze Liu & Haili Zhang & Song Wu & Wenxuan Zhang & Xiaoyu Tang & Yong-Xin Li, 2024. "Rule-based omics mining reveals antimicrobial macrocyclic peptides against drug-resistant clinical isolates," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    10. Jiawen Wang & Faqian He & Xiaoyu Yang, 2021. "Asymmetric construction of acyclic quaternary stereocenters via direct enantioselective additions of α-alkynyl ketones to allenamides," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    11. Wan-Hong Wen & Yue Zhang & Ying-Ying Zhang & Qian Yu & Chu-Chu Jiang & Man-Cheng Tang & Jin-Yue Pu & Lian Wu & Yi-Lei Zhao & Ting Shi & Jiahai Zhou & Gong-Li Tang, 2021. "Reductive inactivation of the hemiaminal pharmacophore for resistance against tetrahydroisoquinoline antibiotics," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    12. Qian Li & Shang Chen & Kui Zhu & Xiaoluo Huang & Yucheng Huang & Zhangqi Shen & Shuangyang Ding & Danxia Gu & Qiwen Yang & Hongli Sun & Fupin Hu & Hui Wang & Jiachang Cai & Bing Ma & Rong Zhang & Jian, 2022. "Collateral sensitivity to pleuromutilins in vancomycin-resistant Enterococcus faecium," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    13. Jiekai Sun & Xu Wang & Ye Gao & Shuangyu Li & Ziwei Hu & Yan Huang & Baoqiang Fan & Xia Wang & Miao Liu & Chunhua Qiao & Wei Zhang & Yipeng Wang & Xingyue Ji, 2024. "H2S scavenger as a broad-spectrum strategy to deplete bacteria-derived H2S for antibacterial sensitization," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    14. Wen-Biao Wu & Bing Xu & Xue-Chun Yang & Feng Wu & Heng-Xian He & Xu Zhang & Jian-Jun Feng, 2024. "Enantioselective formal (3 + 3) cycloaddition of bicyclobutanes with nitrones enabled by asymmetric Lewis acid catalysis," Nature Communications, Nature, vol. 15(1), pages 1-9, December.
    15. Dongquan Zhang & Miaomiao Li & Jiajia Li & Aijun Lin & Hequan Yao, 2021. "Rhodium-catalyzed intermolecular enantioselective Alder–ene type reaction of cyclopentenes with silylacetylenes," Nature Communications, Nature, vol. 12(1), pages 1-7, December.
    16. Andrew M. King & Daniel A. Anderson & Emerson Glassey & Thomas H. Segall-Shapiro & Zhengan Zhang & David L. Niquille & Amanda C. Embree & Katelin Pratt & Thomas L. Williams & D. Benjamin Gordon & Chri, 2021. "Selection for constrained peptides that bind to a single target protein," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    17. Stefan Wiesler & Goh Sennari & Mihai V. Popescu & Kristen E. Gardner & Kazuhiro Aida & Robert S. Paton & Richmond Sarpong, 2024. "Late-stage benzenoid-to-troponoid skeletal modification of the cephalotanes exemplified by the total synthesis of harringtonolide," Nature Communications, Nature, vol. 15(1), pages 1-8, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49629-8. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.