The science of organic synthesis is central to both the discovery and manufacturing of pharmaceuticals and other fine chemicals and the emergence of subdisciplines of biology that are becoming increasingly focused on phenomena at the molecular level (e.g. molecular, synthetic, and chemical biology). Over the last half-century revolutionary advances in synthetic organic chemistry have made it possible to synthesize virtually any molecule given enough time, money, and manpower. However, this is frequently not enough since a lack of practical and cost-effective synthetic access can and does prevent promising drug leads from ever helping patients. The grand challenge for synthetic organic chemistry is therefore to advance the field of synthesis to the point where any molecule can be not only synthesized, but also synthesized in a way that minimizes the cost, time, and manpower required as well as environmental impact. Our group’s research is focused on eliminating synthetic considerations as a barrier to the discovery of new therapeutics.
Chemoselective Hydroxylation of Aliphatic sp3 C–H Bonds Using a Ketone Catalyst and Aqueous H2O2. C. J. Pierce, M. K. Hilinski, Org. Lett. 2014, 16, 6504–6507.
Improving the Affinity of SL0101 for RSK Using Structure-Based Design. R. M. Mrozowski, R. Vemula, B. Wu, Q. Zhang, B. R. Schroeder, M. K. Hilinski, D. E. Clark, S. M. Hecht, G. A. O’Doherty, D. A. Lannigan, ACS Med. Chem. Lett. 2013, 4, 175–179.
Insights into the Inhibition of the p90 Ribosomal S6 Kinase (RSK) by the Flavonol Glycoside SL0101 from the 1.5 Å Crystal Structure of the N-Terminal Doman of RSK2 with Bound Inhibitor. D. Utepbergenov, U. Derewenda, N. Olekhnovich, G. Szukalska, B. Banerjee, M. K. Hilinski, D. A. Lannigan, P. T. Stukenberg, Z. S. Derewenda, Biochemistry 2012, 51, 6499–6510.
Analogues of the RSK Inhibitor SL0101: Optimization of In Vitro Biological Stability. M. K. Hilinski, R. M. Mrozowski, D. E. Clark, D. A. Lannigan, Bioorg. Med. Chem. Lett. 2012, 22, 3244–3247.
Function-Oriented Synthesis: Biological Evaluation of Laulimalide Analogues Derived from a Last Step Cross Metathesis Diversification Strategy. S. L. Mooberry, M. K. Hilinski, E. A. Clark, P. A. Wender Mol. Pharmaceutics 2008, 5, 829–838.