Total synthesis of qinghaosu

Schmid, G.; Hofheinz, W.

doi:10.1021/ja00341a054

Cited by 329Organic Chemistry Synthesis MethodsAdvanced Synthetic Organic ChemistryBiological Activity of Diterpenoids and Biflavonoids

Total synthesis of qinghaosu

Schmid, G., Hofheinz, W.·1983·Journal of the American Chemical Society

DOI 10.1021/ja00341a054

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ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTotal synthesis of qinghaosuG. Schmid and W. HofheinzCite this: J. Am. Chem. Soc. 1983, 105, 3, 624–625Publication Date (Print):February 1, 1983Publication History Published online1 May 2002Published inissue 1 February 1983https://pubs.acs.org/doi/10.1021/ja00341a054https://doi.org/10.1021/ja00341a054research-articleACS PublicationsRequest reuse permissionsArticle Views4456Altmetric-Citations272LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

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Chemical synthesis of artemisinin is far too expensive for many in the Third World because of the structural complexity of the target and the large number of steps in published synthetic routes.
“Although artemisinin can be produced by chemical synthesis [171,228,229,230,231,232,233,234,235,236,237,238,239], the structural complexity of this target and the large number of steps involved in all published synthetic routes render this approach far too expensive for many in the Third World who are most affected by malaria.”
From The Biosynthesis of Artemisinin (Qinghaosu) and the Phytochemistry of Artemisia annua L. (Qinghao) (2010) · cites this paper as [228]

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Hoffmann, R. W., Lanz, J. W., Metternich, R. E., et al. (1987) · Angewandte Chemie International Edition in English · doi:10.1002/anie.198711451 · Cited by 74 · see citing works
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Background
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Martinez, B. C., & Staba, E. J. (1988) · Advances in cell culture · doi:10.1016/b978-0-12-007906-3.50009-7 · Cited by 63 · see citing works
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Johnson, M., & Croteau, R. (1984) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(84)90274-1 · Cited by 61 · see citing works
Laboratory selection of Artemisia annua L. for high artemisinin yielding types
Pras, N., Visser, J. F., Batterman, S., Woerdenbag, H. J., Malingré, T. M., & Lugt, C. (1991) · Phytochemical Analysis · doi:10.1002/pca.2800020208 · Cited by 61 · see citing works
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Kocieński, P., Pontiroli, A., & Liu, Q. (2001) · Journal of the Chemical Society Perkin Transactions 1 · doi:10.1039/b102961b · Cited by 60 · see citing works
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Wan, L. Q., Kong, G., Liu, M., Jiang, M., Cheng, D., & Chen, F. (2022) · Green Synthesis and Catalysis · doi:10.1016/j.gresc.2022.07.007 · Cited by 63 · see citing works
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Oguri, H., Hiruma, T., Yamagishi, Y., Oikawa, H., Ishiyama, A., Otoguro, K., Yamada, H., & Ōmura, S. (2011) · Journal of the American Chemical Society · doi:10.1021/ja200374q · Cited by 58 · see citing works
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Tiwari, M. K., & Chaudhary, S. (2020) · Medicinal research reviews (Print) · doi:10.1002/med.21657 · Cited by 47 · see citing works
A Novel Asymmetric Total Synthesis of (+)-Artemisinin
Constantino, M. G., Beltrame, M., da Silva, G. V. J., & Zukerman-Schpector, J. (1996) · Synthetic Communications · doi:10.1080/00397919608003621 · Cited by 58 · see citing works
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Patel, O. P., Beteck, R. M., & Legoabe, L. J. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113193 · Cited by 56 · see citing works
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Jung, M., Li, X., Bustos, D. A., ElSohly, H. N., & McChesney, J. D. (1989) · Tetrahedron Letters · doi:10.1016/s0040-4039(01)93831-6 · Cited by 56 · see citing works
Morphogenetic variation for artemisinin and volatile oil in Artemisia annua
Gupta, S. K., Singh, P., Bajpai, P., Ram, G., Singh, D., Gupta, M. M., Jain, D. C., Khanuja, S. P., & Kumar, S. (2002) · Industrial Crops and Products · doi:10.1016/s0926-6690(02)00049-3 · Cited by 55 · see citing works
Development of a sensitive monoclonalantibody-based enzyme-linked immunosorbent assay for the antimalaria active ingredient artemisinin in the Chinese herb Artemisia annua L.
He, S., Tan, G., Li, G., Tan, W., Nan, T., Wang, B., Li, Z., & Li, Q. X. (2008) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-008-2527-5 · Cited by 54 · see citing works
Effect of growth regulators and amino acids on artemisinin production in the callus of Artemisia absinthium
Zia, M., Mannan, A., & ., M. F. C. (2007) · Pakistan Journal of Botany · Cited by 52 · see citing works
Synthesis of (+)-artemisinin and (+)-deoxoartemisinin from arteannuin B and arteannuic acid
Nowak, D. M., & Lansbury, P. T. (1998) · Tetrahedron · doi:10.1016/s0040-4020(97)10286-1 · Cited by 51 · see citing works
Isolation of high artemisinin-yielding clones of Artemisia annua
Jain, D. C., Mathur, A. K., Gupta, M. M., Singh, A. K., Verma, R. K., Gupta, A. P., & Kumar, S. (1996) · Phytochemistry · doi:10.1016/s0031-9422(96)00369-x · Cited by 51 · see citing works
Synthetic chemistry fuels interdisciplinary approaches to the production of artemisinin
Corsello, M. A., & Garg, N. K. (2014) · Natural Product Reports · doi:10.1039/c4np00113c · Cited by 53 · see citing works

Authors: Schmid, G., & Hofheinz, W.
Venue: Journal of the American Chemical Society
Publisher: American Chemical Society (ACS)
Published: 1983-02
Volume: 105
Issue: 3
Pages: 624-625
ISSN: 0002-7863 (ISSN-L)
1520-5126
DOI: 10.1021/ja00341a054
OpenAlex: W2020026562
Cited by: 329
References: 0
Citations by year: 2026: 2 · 2025: 5 · 2024: 11 · 2023: 3 · 2022: 7 · 2021: 7 · 2020: 9 · 2019: 10 · 2018: 11 · 2017: 6 · 2016: 12 · 2015: 5 · 2014: 10 · 2013: 13 · 2012: 16
FWCI: 9.15
Type: journal article
Language: en
Open access: closed
Locations: Journal of the American Chemical Society (publishedVersion)
Topics: Physical Sciences › Chemistry › Organic Chemistry › Organic Chemistry Synthesis Methods
Physical Sciences › Chemistry › Organic Chemistry › Advanced Synthetic Organic Chemistry
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biological Activity of Diterpenoids and Biflavonoids
Keywords: artemisinin, total synthesis, sesquiterpene lactones, antimalarial drugs, natural product synthesis

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