Enones from aldehydes and alkenes by carbene-catalyzed dehydrogenated couplings
A new class of chiral pyranone fused indole derivatives were prepared by means of N-heterocyclic carbene (NHC) organocatalysis and demonstrated notable antibacterial activity against Xanthomonas oryzae pv oryzae (Xoo). Bioassays showed that compounds (3S,4R)-5b, (3S,4R)-5d, and (3S,4R)-5l exhibited...
| Main Authors: | , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2024
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| Online Access: | https://hdl.handle.net/10356/174241 |
| _version_ | 1811679419849244672 |
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| author | Tang, Kun Su, Fen Pan, Shijie Lu, Fengfei Luo, Zhongfu Che, Fengrui Wu, Xingxing Chi, Robin Yonggui |
| author2 | School of Chemistry, Chemical Engineering and Biotechnology |
| author_facet | School of Chemistry, Chemical Engineering and Biotechnology Tang, Kun Su, Fen Pan, Shijie Lu, Fengfei Luo, Zhongfu Che, Fengrui Wu, Xingxing Chi, Robin Yonggui |
| author_sort | Tang, Kun |
| collection | NTU |
| description | A new class of chiral pyranone fused indole derivatives were prepared by means of N-heterocyclic carbene (NHC) organocatalysis and demonstrated notable antibacterial activity against Xanthomonas oryzae pv oryzae (Xoo). Bioassays showed that compounds (3S,4R)-5b, (3S,4R)-5d, and (3S,4R)-5l exhibited promising in vitro efficacy against Xoo, with EC50 values of 9.05, 9.71, and 5.84 mg/L, respectively, which were superior to that of the positive controls with commercial antibacterial agents, bismerthiazol (BT, EC50 = 27.8 mg/L) and thiodiazole copper (TC, EC50 = 70.1 mg/L). Furthermore, single enantiomer (3S,4R)-5l was identified as an optimal structure displaying 55.3% and 52.0% curative and protective activities against Xoo in vivo tests at a concentration of 200 mg/L, which slightly surpassed the positive control with TC (curative and protective activities of 47.2% and 48.8%, respectively). Mechanistic studies through molecular docking analysis revealed preliminary insights into the distinct anti-Xoo activity of the two single enantiomers (3S,4R)-5l and (3R,4S)-5l, wherein the (3S,4R)-configured stereoisomer could form a more stable interaction with XooDHPS (dihydropteroate synthase). These findings underscore the significant anti-Xoo potential of these chiral pyranone fused indole derivatives, and shall inspire further exploration as promising lead structures for a novel class of bactericides to combat bacterial infections and other plant diseases. |
| first_indexed | 2024-10-01T03:08:52Z |
| format | Journal Article |
| id | ntu-10356/174241 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:08:52Z |
| publishDate | 2024 |
| record_format | dspace |
| spelling | ntu-10356/1742412024-07-22T02:11:40Z Enones from aldehydes and alkenes by carbene-catalyzed dehydrogenated couplings Tang, Kun Su, Fen Pan, Shijie Lu, Fengfei Luo, Zhongfu Che, Fengrui Wu, Xingxing Chi, Robin Yonggui School of Chemistry, Chemical Engineering and Biotechnology Agricultural Sciences Enones Cross dehydrogenative coupling A new class of chiral pyranone fused indole derivatives were prepared by means of N-heterocyclic carbene (NHC) organocatalysis and demonstrated notable antibacterial activity against Xanthomonas oryzae pv oryzae (Xoo). Bioassays showed that compounds (3S,4R)-5b, (3S,4R)-5d, and (3S,4R)-5l exhibited promising in vitro efficacy against Xoo, with EC50 values of 9.05, 9.71, and 5.84 mg/L, respectively, which were superior to that of the positive controls with commercial antibacterial agents, bismerthiazol (BT, EC50 = 27.8 mg/L) and thiodiazole copper (TC, EC50 = 70.1 mg/L). Furthermore, single enantiomer (3S,4R)-5l was identified as an optimal structure displaying 55.3% and 52.0% curative and protective activities against Xoo in vivo tests at a concentration of 200 mg/L, which slightly surpassed the positive control with TC (curative and protective activities of 47.2% and 48.8%, respectively). Mechanistic studies through molecular docking analysis revealed preliminary insights into the distinct anti-Xoo activity of the two single enantiomers (3S,4R)-5l and (3R,4S)-5l, wherein the (3S,4R)-configured stereoisomer could form a more stable interaction with XooDHPS (dihydropteroate synthase). These findings underscore the significant anti-Xoo potential of these chiral pyranone fused indole derivatives, and shall inspire further exploration as promising lead structures for a novel class of bactericides to combat bacterial infections and other plant diseases. Ministry of Education (MOE) Nanyang Technological University National Research Foundation (NRF) Submitted/Accepted version We acknowledge funding supports from the National Natural Science Foundation of China (Nos. 21732002, 22061007, 22071036, and 22207022); Frontiers Science Center for Asymmetric Synthesis and Medicinal Molecules, National Natural Science Fund for Excellent Young Scientists Fund Program (Overseas), the starting grant of Guizhou University [(2022)47)], Department of Education, Guizhou Province [Qianjiaohe KY number (2020)004]; The 10 Talent Plan (Shicengci) of Guizhou Province ([2016] 5649); Science and Technology Department of Guizhou Province [Qiankehe-jichu-ZK[2022]zhongdian024], ([2018]2802, [2019]1020), QKHJC-ZK[2022]-455; Department of Education of Guizhou Province (QJJ(2022)205); Program of Introducing Talents of Discipline to Universities of China (111 Program, D20023) at Guizhou University; Singapore National Research Foundation under its NRF Investigatorship (NRF-NRFI2016-06) and Competitive Research Program (NRF-CRP22-2019-0002); Ministry of Education, Singapore, under its MOE AcRF Tier 1 Award (RG7/20, RG70/21), MOE AcRF Tier 2 (MOE2019-T2-2-117), and MOE AcRF Tier 3 Award (MOE2018-T3-1-003); a Chair Professorship Grant, and Nanyang Technological University. 2024-03-25T07:47:44Z 2024-03-25T07:47:44Z 2024 Journal Article Tang, K., Su, F., Pan, S., Lu, F., Luo, Z., Che, F., Wu, X. & Chi, R. Y. (2024). Enones from aldehydes and alkenes by carbene-catalyzed dehydrogenated couplings. Chinese Chemical Letters, 35(9), 109495-. https://dx.doi.org/10.1016/j.cclet.2024.109495 1001-8417 https://hdl.handle.net/10356/174241 10.1016/j.cclet.2024.109495 38386000 2-s2.0-85186200502 9 35 109495 en NRF-NRFI2016-06 NRF-CRP22-2019-0002 RG7/20 RG70/21 MOE2019-T2-2-117 MOE2018-T3-1-003 Chinese Chemical Letters © 2024 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. All rights reserved. This article may be downloaded for personal use only. Any other use requires prior permission of the copyright holder. The Version of Record is available online at http://doi.org/10.1016/j.cclet.2024.109495. application/pdf |
| spellingShingle | Agricultural Sciences Enones Cross dehydrogenative coupling Tang, Kun Su, Fen Pan, Shijie Lu, Fengfei Luo, Zhongfu Che, Fengrui Wu, Xingxing Chi, Robin Yonggui Enones from aldehydes and alkenes by carbene-catalyzed dehydrogenated couplings |
| title | Enones from aldehydes and alkenes by carbene-catalyzed dehydrogenated couplings |
| title_full | Enones from aldehydes and alkenes by carbene-catalyzed dehydrogenated couplings |
| title_fullStr | Enones from aldehydes and alkenes by carbene-catalyzed dehydrogenated couplings |
| title_full_unstemmed | Enones from aldehydes and alkenes by carbene-catalyzed dehydrogenated couplings |
| title_short | Enones from aldehydes and alkenes by carbene-catalyzed dehydrogenated couplings |
| title_sort | enones from aldehydes and alkenes by carbene catalyzed dehydrogenated couplings |
| topic | Agricultural Sciences Enones Cross dehydrogenative coupling |
| url | https://hdl.handle.net/10356/174241 |
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