{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:20:27Z","timestamp":1791408027302,"version":"4.3.3"},"reference-count":38,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5720","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2005,4,15]]},"abstract":"<jats:p>Complex antibiotics based on natural products are almost invariably prepared by semisynthesis, or chemical transformation of the isolated natural products. This approach greatly limits the range of accessible structures that might be studied as new antibiotic candidates. Here we report a short and enantioselective synthetic route to a diverse range of 6-deoxytetracycline antibiotics. The common feature of this class is a scaffold of four linearly fused rings, labeled A through D. We targeted not a single compound but a group of structures with the D ring as a site of structural variability. A late-stage, diastereoselective C-ring construction was used to couple structurally varied D-ring precursors with an AB precursor containing much of the essential functionality for binding to the bacterial ribosome. Five derivatives were synthesized from benzoic acid in yields ranging from 5 to 7% over 14 to 15 steps, and a sixth, (-)-doxycycline, was synthesized in 8.3% yield over 18 steps.<\/jats:p>","DOI":"10.1126\/science.1109755","type":"journal-article","created":{"date-parts":[[2005,4,14]],"date-time":"2005-04-14T19:52:56Z","timestamp":1113508376000},"page":"395-398","source":"Crossref","is-referenced-by-count":279,"title":["A Convergent Enantioselective Route to Structurally Diverse 6-Deoxytetracycline Antibiotics"],"prefix":"10.1126","volume":"308","author":[{"given":"Mark G.","family":"Charest","sequence":"first","affiliation":[{"name":"Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian D.","family":"Lerner","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason D.","family":"Brubaker","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dionicio R.","family":"Siegel","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew G.","family":"Myers","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"crossref","unstructured":"C. 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Comm."},{"key":"e_1_3_1_33_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo00395a048"},{"key":"e_1_3_1_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(01)95472-3"},{"key":"e_1_3_1_35_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo00357a047"},{"key":"e_1_3_1_36_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-1980-28963"},{"key":"e_1_3_1_37_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo00869a022"},{"key":"e_1_3_1_38_2","doi-asserted-by":"publisher","DOI":"10.1021\/om00162a016"},{"key":"e_1_3_1_39_2","unstructured":"We thank D. Kahne and C. Walsh for helpful discussions and W. Brubaker (Farmington Pharma Development) and C. Thoma and J. Thanassi (Achillion Pharmacueticals) for antibacterial screening. This work was supported by NIH grant AI48825 NSF predoctoral graduate fellowships (M.G.C. and J.D.B.) and the Deutscher Akademischer Austausch Dienst (C.D.L.). A.G.M. serves on the scientific advisory boards of Vicuron Pharmaceuticals and Miikana Therapeutics and is a consultant for Pfizer. The research described here is independent."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1109755","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T03:48:59Z","timestamp":1704858539000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1109755"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,4,15]]},"references-count":38,"journal-issue":{"issue":"5720","published-print":{"date-parts":[[2005,4,15]]}},"alternative-id":["10.1126\/science.1109755"],"URL":"https:\/\/doi.org\/10.1126\/science.1109755","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,4,15]]}}}