{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T10:14:14Z","timestamp":1784628854517,"version":"3.55.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T00:00:00Z","timestamp":1725235200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T00:00:00Z","timestamp":1725235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22171011, 21977002, 21822101"],"award-info":[{"award-number":["22171011, 21977002, 21822101"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011620","name":"Center for Life Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011620","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Beijing National Laboratory for Molecular Sciences Shenzhen Bay Laboratory"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"DOI":"10.1038\/s41467-024-52134-7","type":"journal-article","created":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T17:02:07Z","timestamp":1725296527000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Divergent syntheses of complex Veratrum alkaloids"],"prefix":"10.1038","volume":"15","author":[{"given":"Yinliang","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runting","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Tian","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2156-3198","authenticated-orcid":false,"given":"Tuoping","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,2]]},"reference":[{"key":"52134_CR1","doi-asserted-by":"crossref","unstructured":"Greenhill, J. V. & Grayshan, P. The Cevane Group of Veratrum Alkaloids; Academic Press: 41, 177\u2212252 (1992).","DOI":"10.1016\/S0099-9598(08)60107-8"},{"key":"52134_CR2","doi-asserted-by":"crossref","unstructured":"Heretsch, P. & Giannis, A. The Veratrum and Solanum Alkaloids; Academic Press: 74, 201\u2212232 (2015).","DOI":"10.1016\/bs.alkal.2014.11.002"},{"key":"52134_CR3","doi-asserted-by":"publisher","first-page":"5934","DOI":"10.3390\/molecules26195934","volume":"26","author":"ML Dirks","year":"2021","unstructured":"Dirks, M. L., Seale, J. T., Collins, J. M. & McDougal, O. M. Review: Veratrum californicum alkaloids. Molecules 26, 5934\u20135953 (2021).","journal-title":"Molecules"},{"key":"52134_CR4","doi-asserted-by":"publisher","first-page":"3553","DOI":"10.1242\/dev.125.18.3553","volume":"125","author":"JP Incardona","year":"1998","unstructured":"Incardona, J. P., Gaffield, W., Kapur, R. P. & Roelink, H. The teratogenic Veratrum alkaloid cyclopamine inhibits sonic hedgehog signal transduction. Development 125, 3553\u20133562 (1998).","journal-title":"Development"},{"key":"52134_CR5","doi-asserted-by":"publisher","first-page":"2743","DOI":"10.1101\/gad.1025302","volume":"16","author":"JK Chen","year":"2002","unstructured":"Chen, J. K., Taipale, J., Cooper, M. K. & Beachy, P. A. Inhibition of hedgehog signaling by direct binding of cyclopamine to smoothened. Genes Dev. 16, 2743\u20132748 (2002).","journal-title":"Genes Dev."},{"key":"52134_CR6","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1039\/C5NP00153F","volume":"33","author":"J Chen","year":"2016","unstructured":"Chen, J. I Only Have eye for ewe: the discovery of cyclopamine and development of hedgehog pathway-targeting drugs. Nat. Prod. Rep. 33, 595\u2013601 (2016).","journal-title":"Nat. Prod. Rep."},{"key":"52134_CR7","doi-asserted-by":"publisher","first-page":"2267","DOI":"10.1016\/S0040-4020(01)97614-8","volume":"20","author":"H Budzikiewicz","year":"1964","unstructured":"Budzikiewicz, H. Zum massenspektroskopischen fragmentierungsverhalten von steroidalalkaloiden. Tetrahedron 20, 2267\u20132278 (1964).","journal-title":"Tetrahedron"},{"key":"52134_CR8","doi-asserted-by":"publisher","first-page":"2079","DOI":"10.1016\/S0031-9422(00)91555-3","volume":"12","author":"TJ Gilbertson","year":"1973","unstructured":"Gilbertson, T. J. Zygacine and zygadenine: the major alkaloids from Zygadenus gramineus. Phytochemistry 12, 2079\u20132080 (1973).","journal-title":"Phytochemistry"},{"key":"52134_CR9","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1161\/01.CIR.13.4.596","volume":"13","author":"E Meilman","year":"1956","unstructured":"Meilman, E. The management of hypertensive cardiovascular disease. Circulation 13, 596\u2013607 (1956).","journal-title":"Circulation"},{"key":"52134_CR10","first-page":"240","volume":"19","author":"Y Zhao","year":"2008","unstructured":"Zhao, Y. et al. Research development towards the pharmacology and toxicology of Veratrum alkaloids. Tradit. Chin. Drug Res. Clin. Pharmacol. 19, 240\u2013242 (2008).","journal-title":"Tradit. Chin. Drug Res. Clin. Pharmacol."},{"key":"52134_CR11","doi-asserted-by":"publisher","first-page":"1716","DOI":"10.1038\/s41401-018-0065-z","volume":"39","author":"X-y Zhang","year":"2018","unstructured":"Zhang, X.-y, Bi, R.-y, Zhang, P. & Gan, Y.-h Vetradine modifies the gating of human voltage-gated sodium channel Nav1.7. Acta Pharmacol. Sin. 39, 1716\u20131724 (2018).","journal-title":"Acta Pharmacol. Sin."},{"key":"52134_CR12","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1021\/acschemneuro.9b00621","volume":"11","author":"RA Craig","year":"2020","unstructured":"Craig, R. A., Garrison, C. E., Nguyen, P. T., Yarov-Yarovoy, V. & Du Bois, J. Veratridine: a Janus-faced modulator of voltage-gated sodium ion channels. Acs. Chem. Neurosci. 11, 418\u2013426 (2020).","journal-title":"Acs. Chem. Neurosci."},{"key":"52134_CR13","doi-asserted-by":"publisher","first-page":"2225","DOI":"10.3390\/ijms23042225","volume":"23","author":"A Gulsevein","year":"2022","unstructured":"Gulsevein, A. et al. Veratridine can bind to a site at the mouth of the channel pore at human cardiac sodium channel NaV1.5. Int. J. Mol. Sci. 23, 2225 (2022).","journal-title":"Int. J. Mol. Sci."},{"key":"52134_CR14","doi-asserted-by":"publisher","first-page":"4521","DOI":"10.1021\/ja00993a048","volume":"89","author":"T Masamune","year":"1967","unstructured":"Masamune, T., Takasugi, M., Murai, A. & Kobayashi, K. C-Nor-D-homo steroids and related alkaloids. IX. Synthesis of jervine and related alkaloids. J. Am. Chem. Soc. 89, 4521\u20134523 (1967).","journal-title":"J. Am. Chem. Soc."},{"key":"52134_CR15","doi-asserted-by":"publisher","first-page":"4523","DOI":"10.1021\/ja00993a049","volume":"89","author":"WS Johnson","year":"1967","unstructured":"Johnson, W. S., DeJongh, H. A. P., Coverdale, C. E., Scott, J. W. & Burckhardt, U. Synthesis of veratramine. J. Am. Chem. Soc. 89, 4523\u20134524 (1967).","journal-title":"J. Am. Chem. Soc."},{"key":"52134_CR16","doi-asserted-by":"publisher","first-page":"4524","DOI":"10.1021\/ja00993a050","volume":"89","author":"WS Johnson","year":"1967","unstructured":"Johnson, W. S., Cox, J. M., Graham, D. W. & Whitlock, H. W. The total synthesis of 17-acetyl-5\u03b1-etiojerva-12,14,16-trien-3\u03b2-ol. J. Am. Chem. Soc. 89, 4524\u20134526 (1967).","journal-title":"J. Am. Chem. Soc."},{"key":"52134_CR17","doi-asserted-by":"publisher","first-page":"5332","DOI":"10.1021\/ja01021a083","volume":"90","author":"JP Kutney","year":"1968","unstructured":"Kutney, J. P. et al. Total synthesis of steroidal derivatives. V. The total synthesis of Veratrum alkaloids. 1. verarine. J. Am. Chem. Soc. 90, 5332\u20135334 (1968).","journal-title":"J. Am. Chem. Soc."},{"key":"52134_CR18","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1021\/ja00445a059","volume":"99","author":"JP Kutney","year":"1977","unstructured":"Kutney, J. P. et al. Synthetic studies in the Veratrum alkaloid series. The total synthesis of C18-functionalized C-nor-D-homo steroid derivatives-valuable intermediates in the total synthesis of Veratrum alkaloids. J. Am. Chem. Soc. 99, 963\u2013964 (1977).","journal-title":"J. Am. Chem. Soc."},{"key":"52134_CR19","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1021\/ja00445a060","volume":"99","author":"JP Kutney","year":"1977","unstructured":"Kutney, J. P. et al. Synthetic studies in the Veratrum alkaloid series. The total synthesis of verticine. J. Am. Chem. Soc. 99, 964\u2013966 (1977).","journal-title":"J. Am. Chem. Soc."},{"key":"52134_CR20","doi-asserted-by":"publisher","first-page":"7911","DOI":"10.1002\/anie.200902520","volume":"48","author":"A Giannis","year":"2009","unstructured":"Giannis, A., Heretsch, P., Sarli, V. & St\u00f6\u00dfel, A. Synthesis of cyclopamine using a biomimetic and diastereoselective approach. Angew. Chem., Int. Ed. 48, 7911\u20137914 (2009).","journal-title":"Angew. Chem., Int. Ed."},{"key":"52134_CR21","doi-asserted-by":"publisher","first-page":"21760","DOI":"10.1021\/jacs.3c09085","volume":"145","author":"M Sofiadis","year":"2023","unstructured":"Sofiadis, M. et al. Convergent total synthesis of (\u2013)-cyclopamine. J. Am. Chem. Soc. 145, 21760\u201321765 (2023).","journal-title":"J. Am. Chem. Soc."},{"key":"52134_CR22","doi-asserted-by":"publisher","first-page":"25086","DOI":"10.1021\/jacs.3c10362","volume":"145","author":"H Shao","year":"2023","unstructured":"Shao, H. et al. Asymmetric synthesis of cyclopamine, a hedgehog (Hh) signaling pathway inhibitor. J. Am. Chem. Soc. 145, 25086\u201325092 (2023).","journal-title":"J. Am. Chem. Soc."},{"key":"52134_CR23","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-49748-2","volume":"15","author":"W Hou","year":"2024","unstructured":"Hou, W. et al. Divergent and gram-scale syntheses of (\u2013)-veratramine and (\u2013)-cyclopamine. Nat. Commun. 15, 5332 (2024).","journal-title":"Nat. Commun."},{"key":"52134_CR24","doi-asserted-by":"publisher","first-page":"16394","DOI":"10.1021\/jacs.1c08756","volume":"143","author":"KJ Cassaidy","year":"2021","unstructured":"Cassaidy, K. J. & Rawal, V. H. Enantioselective total synthesis of (+)-heilonine. J. Am. Chem. Soc. 143, 16394\u201316400 (2021).","journal-title":"J. Am. Chem. Soc."},{"key":"52134_CR25","doi-asserted-by":"publisher","first-page":"1825","DOI":"10.1021\/jacs.3c13492","volume":"146","author":"Y Jin","year":"2024","unstructured":"Jin, Y., Hok, S., Bacsa, J. & Dai, M. Convergent and efficient total synthesis of (+)-heilonine enabled by C\u2013H functionalizations. J. Am. Chem. Soc. 146, 1825\u20131831 (2024).","journal-title":"J. Am. Chem. Soc."},{"key":"52134_CR26","doi-asserted-by":"publisher","first-page":"5150","DOI":"10.1021\/acs.orglett.7b02434","volume":"19","author":"G Stork","year":"2017","unstructured":"Stork, G. et al. Synthetic study toward total synthesis of (\u00b1)\u22124-methylenegermine. Org. Lett. 19, 5150\u20135153 (2017).","journal-title":"Org. Lett."},{"key":"52134_CR27","doi-asserted-by":"publisher","first-page":"1913","DOI":"10.1021\/ja01517a033","volume":"81","author":"SM Kupchan","year":"1959","unstructured":"Kupchan, S. M. & Narayanan, C. R. Veratrum alkaloids. XXVIII. The structure and configuration of germine. J. Am. Chem. Soc. 81, 1913\u20131921 (1959).","journal-title":"J. Am. Chem. Soc."},{"key":"52134_CR28","doi-asserted-by":"publisher","first-page":"2242","DOI":"10.1021\/ja01494a038","volume":"82","author":"SM Kupchan","year":"1960","unstructured":"Kupchan, S. M. et al. Veratrum alkaloids. XXXVIII. The structure and configuration of protoverine. J. Am. Chem. Soc. 82, 2242\u20132251 (1960).","journal-title":"J. Am. Chem. Soc."},{"key":"52134_CR29","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1002\/hlca.200790078","volume":"90","author":"J Tang","year":"2007","unstructured":"Tang, J. et al. Four new germine esters from Veratrum dahuricum. Helv. Chim. Acta 90, 769\u2013775 (2007).","journal-title":"Helv. Chim. Acta"},{"key":"52134_CR30","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1248\/cpb.59.909","volume":"59","author":"N Tanaka","year":"2012","unstructured":"Tanaka, N., Suto, S. & Kobayashi, J. Veramadines A and B, new steroidal alkaloids from veratrum maackii var. japonicum. Chem. Pharm. Bull. 59, 909\u2013912 (2012).","journal-title":"Chem. Pharm. Bull."},{"key":"52134_CR31","doi-asserted-by":"publisher","first-page":"20202","DOI":"10.1021\/jacs.3c08039","volume":"145","author":"Y Guo","year":"2023","unstructured":"Guo, Y. et al. Enantioselective total synthesis of (\u2013)-zygadenine. J. Am. Chem. Soc. 145, 20202\u201320207 (2023).","journal-title":"J. Am. Chem. Soc."},{"key":"52134_CR32","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1021\/ja01534a053","volume":"80","author":"RB Woodward","year":"1958","unstructured":"Woodward, R. B. & Brutcher, F. V. cis-Hydroxylation of a synthetic steroid intermediate with iodine, silver acetate and wet acetic acid. J. Am. Chem. Soc. 80, 209\u2013211 (1958).","journal-title":"J. Am. Chem. Soc."},{"key":"52134_CR33","doi-asserted-by":"publisher","first-page":"11304","DOI":"10.1021\/ja304547s","volume":"134","author":"C Cheng","year":"2012","unstructured":"Cheng, C. & Brookhart, M. Iridium-catalyzed reduction of secondary amides to secondary amines and imines by diethylsilane. J. Am. Chem. Soc. 134, 11304\u201311307 (2012).","journal-title":"J. Am. Chem. Soc."},{"key":"52134_CR34","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1021\/jo00110a034","volume":"60","author":"DL Boger","year":"1995","unstructured":"Boger, D. L. & McKie, J. A. An efficient synthesis of 1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indol\u22124-one (CBI): an enhanced and simplified analog of the CC-1065 and duocarmycin alkylation subunits. J. Org. Chem. 60, 1271\u20131275 (1995).","journal-title":"J. Org. Chem."},{"key":"52134_CR35","first-page":"161","volume":"34","author":"KA El Sayed","year":"1996","unstructured":"El Sayed, K. A., McChesney, J. D., Halim, A. F., Zaghloul, A. M. & Lee, I.-S. A study of alkaloids in Veratrum viride Aiton. Pharm. Biol. 34, 161\u2013173 (1996).","journal-title":"Pharm. Biol."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-52134-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-52134-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-52134-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T17:03:07Z","timestamp":1725296587000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-52134-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,2]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["52134"],"URL":"https:\/\/doi.org\/10.1038\/s41467-024-52134-7","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,2]]},"assertion":[{"value":"28 June 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 August 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 September 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"7639"}}