Background:

• 2003-2004 Hellman Foundation Fellow

The principal focus of my research is to use the power of organic synthesis to study problems of biological and medicinal interest. The templates for our work are found in the vast array of unique substances provided by nature. Natural products offer the opportunity to advance the art of organic synthesis, enhance our knowledge of chemical reactivity, while, at the same time, positioning the synthetic chemist to have a significant impact in emerging fields of biology and medicine. Broadly described, our efforts encompass two major areas of interest: 1) the identification of novel antibacterial agents that function via inhibition of bacterial cell wall (peptidoglycan) biosynthesis, and 2) the synthesis and biological study of novel agents for use in cancer chemotherapy. Cell wall biosynthesis is an essential function for the viability of bacterial cells. Since the biosynthetic pathway is unique to bacterial cells, any agent that interrupts a single enzymatic event in the cell wall biosynthetic cascade might be expected to display selective toxicity toward bacterial cells. Nature has provided a variety of chemotherapeutic agents that act at various points within the cell wall biosynthetic pathway. Our goal is to leverage our expertise in the chemical synthesis of the biosynthetic intermediates to better understand the mechanisms by which these novel natural products induce their antibiotic activity. A second area of interest is in the synthesis and study of agents with applications in cancer chemotherapy. Although our principal interest is in marine-derived agents that inhibit actin polymerization, we are also interested in the dynamics of DNA recognition and chemical structure. Our synthetic targets are selected based upon their novelty, complexity, and mechanism of action. We strive to develop novel synthetic methodology and to provide a challenging and stimulating research environment.

Selected Publications:

Wohlrab, A.; Lamer, R.; VanNieuwenhze, M. S. "Total Synthesis of Plusbacin A3 : A Depsipeptide Antibiotic Active Against Vancomycin-Resistant Bacteria," J. Am. Chem. Soc. 2007 , 129, 4175-4177.

Guzmán-Martínez, A.; Lamer, R.; Narayan; VanNieuwenhze, M. S.* "Total Synthesis of Lysobactin," J. Am. Chem. Soc . 2007, 129 , 6017-6021.

Narayan, R. S.; VanNieuwenhze, M. S. "Synthesis of Substrates and Biochemical Probes for Study of the Peptidoglycan Biosynthetic Pathway, " Eur. J. Org. Chem. 2007, 1399-1414.

Perelman, L. A.; Schwarz, M. P.; Wohlrab, A. VanNieuwenhze, M. S.; Sailor, M. J. "A Simplified Biomolecule Attachment Strategy for Biosensing using a Porous Si Oxide Interferometer," Phys. Stat. Sol. (a) 2007, 204, 1394-1398.

Guzmán-Martínez, A.; VanNieuwenhze, M. S. "An Efficient Synthesis of an Orthogonally-Protected β-Hydroxyasparagine," Synlett 2007, 1513-1516.

Narayan, R. S.; VanNieuwenhze, M. S. "Versatile and Stereoselective Syntheses of Orthogonally Protected β-Methylcysteine and β-Methyllanthionine," Org. Lett. 2005, 7, 2655.

Fahy, E.; Subramaniam, S.; Brown, H. A.; Glass, C. K.; Merrill, Jr, A. H.; Murphy, R. C.; Raetz, C. R. H.; Russell, D. W.; Seyama, Y.; Shaw, W.; Shimizu, T.; Spener, F.; van Meer, G.; VanNieuwenhze, M. S., White, S. H.; Witztum, J. L.; Dennis, E. A. "A Comprehensive Classification System for Lipids," J. Lipid Res. 2005, 46, 839.