SIOC English
化学学报
高级检索

化学学报 >

0 0

DOI: https://doi.org/10.6023/A26060210

研究论文

Coniochaetone类天然产物的克级规模合成★

  • 李铁鹏 ,
  • 何海兵 ,
  • 杨鲍潮 ,
  • 高栓虎
展开
  • a华东师范大学化学与分子工程学院 石油化工分子转化与反应工程全国重点实验室 上海市绿色化学与化工过程绿色化重点实验室 上海 200062;
    b上海市分子智造前沿科学基地 上海 200062
★“纪念兰州大学化学学科创建80 周年”专辑

收稿日期: 2026-06-19

  网络出版日期: 2026-07-21

基金资助

国家自然科学基金 (No. 22225105, 22201076, 22301078), 国家重点研发计划 (2022YFC2804200), “中央高校基本科研业务费专项资金”

收起

Gram-scale Synthesis of Coniochaetones

  • Tiepeng Li ,
  • Haibing He ,
  • Baochao Yang ,
  • Shuanhu Gao
Expand
  • aState Key Laboratory of Petroleum Molecular & Process Engineering, Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062;
    bShanghai Frontiers Science Center of Molecule Intelligent Syntheses, Shanghai 200062

Received date: 2026-06-19

  Online published: 2026-07-21

Supported by

National Natural Science Foundation of China (22225105, 22201076, 22301078), the National High Technology Research and Development Program of China(2022YFC2804200), “the Fundamental Research Funds for the Central Universities”

Fold

摘要

Coniochaetone类天然产物是一类具有稠合环戊烷环的色酮类衍生物,最早从粪生真菌Coniochaeta saccardoi中分离获得。其中,coniochaetone A表现出显著的细胞毒性和抗紫色色杆菌活性。本研究中,我们利用Ramachary发展的还原性Knoevenagel缩合/环化反应高效构建了三环核心骨架,随后经过苄位氧化和官能团转化完成了coniochaetone类天然产物的合成,并实现了其克级规模的放大,为其生物活性研究奠定基础。

关键词： coniochaetones; 缩合; 苄位氧化; 克级规模合成

本文引用格式

李铁鹏 , 何海兵 , 杨鲍潮 , 高栓虎 . Coniochaetone类天然产物的克级规模合成★[J]. 化学学报, 0 : 0 . DOI: 10.6023/A26060210

Abstract

Coniochaetones are chromone derivatives bearing a fused cyclopentanoid ring, originally isolated from the coprophilous fungus Coniochaeta saccardoi. In terms of biological activity, coniochaetone A displays potent cytotoxicity and activity against Chromobacterium violaceum. In our previous work, we accomplished the syntheses of tetrahydroxanthone natural products bearing a fused cyclohexane ring, including diversonol, kibdelone C, ascherxanthone A, and rugulotrosin A. Among these, the synthesis of rugulotrosin A featured a Knoevenagel condensation/6π-electronic cyclization cascade followed by an aromatization process. Our initial synthetic plan targeted the pivotal intermediate 17 via a palladium-catalyzed carbonylative cross-coupling of 18 and 19. However, this approach was plagued by regioselectivity issues at the 1,3-dicarbonyl nucleophile: C-attack furnished the desired tricarbonyl 17, whereas O-attack gave benzoic enol ester 24. Although 24 could, in principle, be converted to 17 via a Fries-type rearrangement, this transformation proved unsuccessful in our hands, with 24 predominating. Consequently, we revised our strategy toward 17 using a Roskamp reaction/Dieckmann condensation sequence. Unfortunately, under Lewis acid conditions, the Roskamp protocol exclusively delivered the 1,2-aryl migration product 27 rather than the desired 1,2-hydride shift adduct. We therefore turned to Ramachary’s reductive Knoevenagel condensation/cyclization, which efficiently constructed the tricyclic core framework. The subsequent installation of the benzylic oxidation state proved challenging, as most oxidizing conditions led to decomposition of the substrate. After extensive screening, we successfully introduced a tert-butylperoxy group at the benzylic position under the conditions of palladium on activated carbon (Pd/C), tert-butyl hydroperoxide (TBHP), and potassium carbonate (K2CO3). This intermediate was then converted to ketone 30 via Kornblum-DeLaMare rearrangement. Final deprotection of the methyl ether delivered coniochaetone A (1). Reduction of the C-1 carbonyl group in 1 afforded coniochaetone B (2), and subsequent selective methylation of the secondary alcohol furnished coniochaetone C (3) under mild conditions of silver oxide (Ag2O) and methyl iodide (MeI). Following the establishment of this efficient route, we successfully achieved the gram-scale synthesis of coniochaetones, laying the foundation for further biological activity studies.

Key words： coniochaetones; condensation; benzylic oxidation; gram-scale synthesis

参考文献

[1] (a) Wang H.-j.; Gloer J. B.; Scott J. A.; Malloch D. Tetrahedron Lett.1995, 36, 5847-5850. (b) Khamthong, N.; Rukachaisirikul, V.; Phongpaichit, S.; Preedanon, S.; Sakayaroj, J. Tetrahedron 2012, 68, 8245-8250. (c) Deng, L.; Niu, S.; Liu, X.; Che, Y.; Li, E. Fitoterapia 2013, 89, 8-14. (d) González‐Andrade, M.; DeláValle, P.; Macías‐Rubalcava, M.; L; Sosa‐Peinado, A.; Del Carmen González, M.; Mata, R. Chem. Biodivers. 2013, 10, 328-337. (e) Wei, X.; Feng, C.; Li, X. H.; Mao, X. X.; Luo, H. B.; Zhang, D. M.; Rong, L.; Xie, Z. Y.; Yu, X.; Li, J.; Ye, W. C.; Huang, X. J.; Zhang, C. X. Chem. Biodivers. 2019, 16, e1900052. (f) Salendra, L.; Lin, X.; Chen, W.; Pang, X.; Luo, X.; Long, J.; Liao, S.; Wang, J.; Zhou, X.; Liu, Y.; Yang, B. Nat. Prod. Res. 2019, 35, 900-908. (g) Trisuwan, K.; Rukachaisirikul, V.; Borwornwiriyapan, K.; Phongpaichit, S.; Sakayaroj, J. Tetrahedron Lett. 2014, 55, 1336-1338. (h) Kornsakulkarn, J.; Saepua, S.; Komwijit, S.; Rachtawee, P.; Thongpanchang, C. Tetrahedron 2014, 70, 2129-2133. (i) Xia, M.-W.; Cui, C.-B.; Li, C.-W.; Wu, C.-J.; Peng, J.-X.; Li, D.-H. Mar. Drugs 2015, 13, 5219-5236. (j) Liu, F.-a.; Lin, X.; Zhou, X.; Chen, M.; Huang, X.; Yang, B.; Tao, H. Molecules 2017, 22, 1999. (1k) Bashiri, S.; Abdollahzadeh, J.; Di Lecce, R.; Alioto, D.; Górecki, M.; Pescitelli, G.; Masi, M.; Evidente, A. J. Nat. Prod. 2020, 83, 447-452. (l) Pang, X.; Wang, P.; Liao, S.; Zhou, X.; Lin, X.; Yang, B.; Tian, X.; Wang, J.; Liu, Y. Phytochemistry 2022, 202, 113311. (m) Zhang, A.-L.; Zou, Z.-B.; Guo, Y.-Q.; Su, W.-S.; Xie, C.-L.; Li, L.-S.; Gao, C.-H.; Yang, X.-W. Chem. Biodivers. 2026, 23, e71299.
[2] Wang C.-N.; Lu H.-M.; Gao C.-H.; Guo L.; Zhan Z.-Y.; Wang J.-J.; Liu Y.-H.; Xiang S.-T.; Wang J.; Luo, X.-W. Nat. Prod. Res.2020, 35, 5596-5603.
[3] Murali M.; Ahmed F.; Gowtham H. G.; Aribisala J. O.; Abdulsalam R. A.; Shati A. A.; Alfaifi M. Y.; Sayyed R. Z.; Sabiu S.; Amruthesh, K. N. Sci. Rep.2023, 13, 15505.
[4] Adpressa D. A.; Stalheim K. J.; Proteau P. J.; Loesgen, S. ACS Chem. Biol.2017, 12, 1842-1847.
[5] Bashiri S.; Abdollahzadeh J.; Di Lecce R.; Alioto D.; Górecki M.; Pescitelli G.; Masi M.; Evidente, A. J. Nat. Prod.2020, 83, 447-452.
[6] (a) Xiao Z.; Cai S.; Shi Y.; Yang B.; Gao, S. Chem. Commun. 2014, 50,5254-5257. (b) Xiao, Z.; Li, Y.; Gao, S.Org. Lett. 2017, 19, 1834-1837. (c) Dai, Y.; Ma, F.; Shen, Y.; Xie, T.; Gao, S. Org. Lett. 2018, 20, 2872-2875. (d) Chen, J.; Li, Y.; Xiao, Z.; He, H.; Gao, S. Org. Lett. 2020, 22, 1485-1489.
[7] Mori K. A.,G.; Monti, H.Synlett 1998, 259.
[8] Ramachary D. B.; Reddy Y. V.; Kishor, M. Org. Biomol. Chem.2008, 6, 4188-4197.
[9] Seth S.; Jhulki S.; Moorthy, J. N. Eur. J. Org. Chem.2013, 2013, 2445-2452.
[10] (a) Korsager S.; Nielsen D. U.; Taaning R. H.; Lindhardt A. T.; Skrydstrup, T. Chem. Eur. J.2013, 19, 17687-17691. (b) Nielsen, D. U.; Korsager, S.; Lindhardt, A. T.; Skrydstrup, T. Adv. Synth. Catal. 2014, 356, 3519-3524. (c) Korsager, S.; Nielsen, D. U.; Taaning, R. H.; Skrydstrup, T. Angew. Chem. Int. Ed. 2013, 52, 9763-9766. (d) Lu, W.; Li, Y.; Wang, C.; Xue, D.; Chen, J.-G.; Xiao, J. Org. Biomol. Chem. 2014, 12, 5243-5249. (e) Jensen, M. T.; Juhl, M.; Nielsen, D. U.; Jacobsen, M. F.; Lindhardt, A. T.; Skrydstrup, T. J. Org. Chem. 2016, 81, 1358-1366.
[11] (a) Wu Q.-G.; Liang R.-L.; Yang, J.-F. Pestic. Biochem. Physiol.2025, 215, 106692;(b) Ndikuryayo, F.; Kang, W.-M.; Wu, F.-X.; Yang, W.-C.; Yang, G.-F. Eur. J. Med. Chem. 2019, 166, 22-31.
[12] Schmidt A.; Boland, W. J. Org. Chem.2007, 72, 1699-1706.
[13] Lewis A. R.; Reber, K. P. Tetrahedron Lett.2016, 57, 1083-1086.
[14] Nobuta T.; Tsuchiya N.; Suto Y.; Yamagiwa, N. Org. Biomol. Chem.2024, 22, 703-707.
[15] Yin J.; Kong L.; Wang C.; Shi Y.; Cai S.; Gao, S. Chem. Eur. J.2013, 19, 13040-13046.
[16] Trost B. M.; Shen H. C.; Dong L.; Surivet J.-P.; Sylvain, C. J. Am. Chem. Soc.2004, 126, 11966-11983.
[17] Kirillova M. S.; Muratore M. E.; Dorel R.; Echavarren, A. M. J. Am. Chem. Soc.2016, 138, 3671-3674.
[18] (a) Buchner E.; Curtius, T. Ber. Dtsch. Chem. Ges.1885, 18, 2371-2377. (b) Fang T.; Liu C. Chem. Catal.2024, 4, 100872.
[19] Bugaut X.; Roulland, E. Eur. J. Org. Chem.2012, 2012, 908-912.
[20] (a) Amancha P. K.; Liu H.-J.; Ly T. W.; Shia, K.-S. Eur. J. Org. Chem.2010, 2010, 3473-3480. (b) Yang, B.; Li, G.; Wang, Q.; Zhu, J. J. Am. Chem. Soc. 2023, 145, 5001-5006. (c) Yamada, K.; Kato, M.; Takahashi, S.; Izawa, H.; Murakami, K.; Yamada, H.; Katsuta, R.; Ishigami, K.; Wakamori, S. J. Org. Chem. 2026, 91, 3188-3195. (d) Ramachary, D. B.; Vijayendar Reddy, Y. J. Org. Chem. 2010, 75, 74-85.
[21] Zhao, H.; Ponnam, D.; Li Y.; Li, M.; Yang, J.; Chen J.; Fan, B. Acta Chim. Sinica, 2026, 84, 293-298 (in Chinese). (赵红艳, Ponnam, Ponnam, 李亚彤, 李明珠, 杨晶雯, 陈景超, 樊保敏, 化学学报, 2026, 84, 293-298.)
[22] Endo Y.; Hasegawa M.; Matsui T.; Yagi H.; Hino S.; Mazaki Y. Org. Lett.2014, 16, 5608-5611.
[23] Wang Y.; Huang S.-X.; Xia P.; Xia Y.; Yang Z.-Y.; Kilgore N.; Morris-Natschke S. L.; Lee, K.-H. Bioorg. Med. Chem. Lett.2007, 17, 4316-4319.
[24] Liu J.; Hu K.-F.; Qu J.-P.; Kang Y.-B. Org. Lett.2017, 19, 5593-5596.
[25] Ortiz G.; Liu P.; Naing S. H. H.; Muller V. R.; Miller, E. W. J. Am. Chem. Soc.2019, 141, 6631-6638.
[26] Lee H.-Y.; Sha, C.-K. J. Org. Chem.2011, 77, 598-605.
[27] Han X.; Wan C.; Li X.; Li H.; Yang D.; Du S.; Xiao Y.; Qin, Z. Bioorg. Med. Chem. Lett.2015, 25, 2438-2441.
[28] (a) Zaed A. M.; Swift M. D.; Sutherland, A. Org. Biomol. Chem.2009, 7, 2678-2680. (b) Yu, J.-Q.; Corey, E. J. Org. Lett. 2002, 4, 2727-2730. (c) Yu, J.-Q.; Corey, E. J. J. Am. Chem. Soc. 2003, 125, 3232-3233. (d) Yu, J.-Q.; Wu, H.-C.; Corey, E. J. Org. Lett. 2005, 7, 1415-1417.
[29] (a) Wen, G.; Gu, S.; He, H.; Gao, S. Chin. J. Org. Chem. 2025, 45, 977-987 (in Chinese). (文国恩,谷硕,何海兵,高栓虎,有机化学, 2025, 45, 977-987.) (b) Huang, J.; Yin, R.; Cao, T. Acta Chim. Sinica, 2025, 83, 1424-1434 (in Chinese). (黄俊, 尹蓉, 曹婷婷, 化学学报, 2025, 83, 1424-1434.)
[30] (a) Zhang H.-Y.; Ge C.; Zhao J.; Zhang Y. Org. Lett.2017, 19, 5260-5263. (b) Chen Y.; Tian T.; Li, Z. Org. Chem. Front.2019, 6, 632-636.
[31] (a) Lee S.; Paek S.-M.; Yun H.; Kim N.-J.; Suh Y.-G. Org. Lett.2011, 13, 3344-3347. (b) Kuethe J. T.; Wong A.; Wu J.; Davies I. W.; Dormer P. G.; Welch C. J.; Hillier M. C.; Hughes D. L.; Reider, P. J. J. Org. Chem.2002, 67, 5993-6000.
[32] Liu, X.; Xu, T.; Qin, Y. Chin. J. Org. Chem., 2025, 45, 3098-3112 (in Chinese). (刘小宇, 许庭瑞, 秦勇, 有机化学, 2025, 45, 3098-3112.)
[33] Schmidt B.; Hauke S.Eur. J. Org. Chem. 2014, 2014, 1951-1960.
[34] Li, T.; He, H.; Gao, S. CN 202511976707.0, 2025 (in Chinese). (李铁鹏,何海兵,高栓虎, CN 202511976707.0, 2025. )
Options
文章导航

/

〈 〉