Merritt B. Andrus
BS, Brigham Young University (1986)
Ph.D., University of Utah (1986-1991)
NIH Postdoctoral Fellow, Harvard University (1991-1993)
Assistant Professor, Purdue University (1993-1997)
Efforts in our lab are focused on methods for the synthesis of biologically active natural products that possess unique structures and potential for combinatorial library construction and screening. New methods include metal catalyzed couplings and condensations to assemble key intermediates. Libraries of structural variants are then made and used to probe receptor binding and improve activity.
Recent work includes the synthesis of the polyene stipiamide, a new reversal agent of multidrug resistance (MDR). Various non-natural compounds have been made that restore the potency of cancer drugs to resistant cancer cell lines. New synthetic methods include a copper-tin conjugate addition and palladium acetylene couplings. A combinatorial library, an array of variants using a new solution-phase based approach, has been made and screened based on a simplified stipiamide motif. More potent compounds were identified, and characterized. New oligomeric MDR reversal agents are also under consideration along with photoaffinity labels for the causative MDR protein, Pgp.
Other targets include geldanamycin, a potent anti-cancer agent with a challenging array of functionality. A new anti glycolate asymmetric aldol reaction has been developed to generate the 1,2-methoxy, hydroxy functionality. Computer aided variants will also be made and tested for binding to heat shock protein 90, a key chaperon of oncogenic kinases, and known target for geldanamycin. A far more simple, yet no less important target is the stilbene resveratrol, the suspected causative agent of the 'French Paradox.' Diets rich in foods that contain this material, grapes in particular, lead to lower rates of cancer and heart disease. New coupling methods and strategies were developed to produce this material that will now be used to produce structural variants for various screens. General synthetic methods with broad application are also under development using new ligands for copper. Asymmetric allylic oxidation of olefins using peresters gives allyl ester products in high enantioselectivity. Mechanistic studies and new transformations that have not received great attention in the past are now under study.
Wong, Y., Osmond, G., Brewer, K.I., Tyler, D.S., and Andrus, M.B. “Synthesis of 4'-ester analogs of resveratrol and their evaluation in malignant melanoma and pancreatic cell lines.” Bioorg Med Chem Lett. 20(3) (2010):1198-201.
Andrus, M.B., Christiansen, M.A., Hicken, E.J., Gainer, M.J., Bedke, D.K., Harper, K.C., Mikkelson, S.R., Dodson, D.S., and Harris, D.T. “Phase-transfer-catalyzed asymmetric acylimidazole alkylation.” Org Lett. 9(23) (2007):4865-8.
Andrus, M.B., Hicken, E.J., Stephens, J.C., and Bedke, D.K. “Total synthesis of the hydroxyketone kurasoin A using asymmetric phase-transfer alkylation.” J Org Chem. 71(22) (2006):8651-4.
- NSF Career Award (1995)
- Procter & Gamble University Exploratory Research Award (1996)