Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 15 April 2005:
Vol. 308. no. 5720, pp. 395 - 398
DOI: 10.1126/science.1109755
Prev | Table of Contents | Next

Reports

A Convergent Enantioselective Route to Structurally Diverse 6-Deoxytetracycline Antibiotics

Mark G. Charest, Christian D. Lerner, Jason D. Brubaker, Dionicio R. Siegel, Andrew G. Myers*

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.

Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.

* To whom correspondence should be addressed. E-mail: myers{at}chemistry.harvard.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Engineered Biosynthesis of a Novel Amidated Polyketide, Using the Malonamyl-Specific Initiation Module from the Oxytetracycline Polyketide Synthase.
W. Zhang, B. D. Ames, S.-C. Tsai, and Y. Tang (2006)
Appl. Envir. Microbiol. 72, 2573-2580
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)