Research in our lab focuses on synthetic organic chemistry and its applications to biological problems. In the area of diversity-oriented synthesis, we are developing new synthetic routes and strategies to access small molecules containing structural motifs commonly found in biologically active natural products. These efforts provide exciting opportunities to develop new synthetic methodologies and insights into chemical reactivity. After efficient, flexible synthetic routes have been developed, discovery libraries are synthesized for screening against promising new targets in cancer and infectious diseases through collaborations with other labs in the Tri-Institutional program and the NIH Molecular Libraries Initiative.
We are also engaged in a complementary program involving rational design of novel antibiotics that target natural product biosynthetic pathways. We use mechanistic and structural information about individual targets of interest to design small molecule inhibitors. Among these are compounds that block siderophore biosynthesis pathways critical for bacterial iron uptake and virulence. We again leverage synergistic multidisciplinary collaborations with biologists in our Tri-Institutional program and elsewhere in these efforts. More information about these projects is available below.
Key Review Articles
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Cisar, J. S.; Tan, D. S.* "Small molecule inhibition of microbial natural product biosynthesis – An emerging antibiotic strategy." Chem. Soc. Rev. 2008, 37, 1320–1329.
[ Abstract | PDF | PMC ]
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Tan, D. S.* "Diversity-oriented synthesis: Exploring the intersections between chemistry and biology." Nature Chem. Biol. 2005, 1, 74–84.
[ Abstract | PDF ]
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