Browder Research Group, Spring 2012

Mike Hirschman, Amanda Jevons, Melanie Hipple, Ky Mickelsen, Chris Oulton

 

Application procedure for undergraduate research positions.

Prosepective graduate students should consult the department web page.

 

The Browder Group in interested in developing novel methodologies for the synthesis of organic compounds of medicinal interest, as well as designing and preparing new materials for use in alternative energy solutions. Our traditional synthetic work employs heterocyclic and related structures in generating both cyclic and acyclic products. Among our target molecules are potential inhibitors of bacterial growth; azapeptides, which are known antiviral agents; and an approach to the bryozoan isolate myriaporone 4. In addition, we have found a solid polymer electrolyte formulation that, when employed in a structural supercapacitor, can be used to store power in a thin, lightweight material.

 

Design, synthesis, and evaluation of inhibitors of bacterial amino acid biosynthesis. With the increase in antibiotic resistant strains of bacteria in recent years, it is more important now than ever to discover compounds that work against previously untargeted bacterial metabolic pathways. The "essential" amino acids (those that are consumed by mammals but produced by plants and bacteria) present unexploited biosynthetic pathways whose function may be disrupted to diminish bacterial growth. The Gage group has demonstrated that bacteria lacking specific genes for amino acid biosynthesis do not grow even in rich media. Our group designed and synthesized libraries of potential inhibitors of specific enzymes in amino acid biosynthetic pathways. These compounds are then screened for biological activity in the Gage laboratory. The screening data is then used to refine our design to generate additional libraries of inhibitors.

Fabrication of supercapacitors featuring solid polymer electrolytes. Multifunctional materials are of great interest because of their ability to "multitask." In conjuction with Dr. Constantin Ciocanel in Mechanical Engineering, we have designed and fabricated a structural supercapacitor, a power storage material that is also capable of supporting mass, encasing electronics, or otherwise providing shape and form. This material could be used, for example, to store the energy from a solar panel within the framing of the panel itself. As a result, the batteries to store the generated electricity are obsolete. A key component of the supercapacitor is a solid polymer electrolyte that both provides physical form and strength as well as conducts electricity for charging and discharging the material. Our ongoing work includes optimization of the solid polymer electrolyte by investigating appropriate polymer formulations along with ideal levels of conductive ions.

Methodology for the total synthesis of myriaporone 4. Myriaporone 4 is a potent anticancer compound found in organisms in delicate marine ecosystems.  Because harvest from the natural source would be both ecologically destructive and inefficient, the compound must be synthesized in the laboratory for further studies and development as a chemotherapeutic agent.  The Browder Group is developing a new, efficient reaction sequence that will facilitate the synthesis of myriaporone 4 or its analogs.  Our two-step sequence couples simple, acyclic precursors under standard esterification conditions, and then uses a known cyclization reaction to generate a fused bicyclic system, which is applicable to the synthesis of myriaporone 4 and related compounds. Notably, this process allows us to introduce a great deal of molecular complexity in very few laboratory manipulations, which will increase the efficiency of synthesis of the target natural product.

Azapeptide synthesis. A reaction discovered in our laboratory that generated sought-after and difficult to synthesize hydrazone carbamates.  These substituted hydrazones can be used as precursors to azapeptides, desirable medicinal compounds with antiviral and antihypertensive activities.  Our method will allow for a great variety of carbon backbones that may be employed in synthesis of hydrazone carbamates, and subsequently a large number of different azapeptide products that will be examined for biological activity.

Synthesis of oximes. Oximation of alpha,beta-unsaturated oxime compounds is often complicated by competing 1,4-addition and other side reactions.  We have found that use of inorganic lithium bases in simple hydroxyamine condensation reactions allows for facile oximation of alpha,beta-unsaturated ketones without forming 1,4-addition products.  The method employs readily available and inexpensive reagents, and requires lower reaction times and temperatures than the hydroxylamine condensation conditions typically used.

Copper-induced cyclization reactions of oximes. Isoxazoles are finding increasing applications in medicinal formulations, from antibiotics to vascular and neuroactive drugs. We have developed a method for isoxazole synthesis that is facile and employs inexpensive and readily available materials. The method is applicable to a number of different substitution patterns, which allows for the production of a wide variety of isoxazole products. However, the unusual reaction conditions warrant continued exploration of the reaction to better elucidate the course of the reaction..

 

Recent publications (* undergraduate coauthor)

“Copper Induced Cyclization of α,β-Unsaturated Carbonyl Compounds to Isoxazoles.” Cindy C. Browder, Christopher B. Moss,* Matthew B. Kraft,* Paige L. Petrucka,* Tara S. Morey,* Christopher W. Leach,* and Nicholas C. Gearhart,* Letters in Organic Chemistry, 2011, 8, 229-233.

“A method for the selective formation of dimethyl acetals in the presence of hydroxylamine.” Mickelsen, K. J.;* Tajc, C. M.;* Greenwood, K. R.;* Browder, C. C. Synth. Commun. 2012, 42, 186-194. DOI: 10.1080/00397911.2010.523156

“Recent Advances in Intramolecular Nitrile Oxide Cycloadditions in the Synthesis of 2-Isoxazolines.” Browder, C. C. Current Org. Synth. 2011, 8, 628-644.

“Biosynthesis of the 3,4-Dihydroxybenzoate Moieties of Petrobactin by Bacillus anthracis.” Andrew T. Koppisch, Kinya Hotta, David T. Fox, Christy E. Ruggiero, Chu-Young Kim, Timothy Sanchez, Srinivas Iyer, Cindy C. Browder, Pat J. Unkefer, and Clifford J. Unkefer. J. Org. Chem. 2008, 73, 5759-5765. DOI: 10.1021/jo800427f

 

Dr. Browder maintains a strong commitment to undergraduate involvement in laboratory research. Any current or prospective NAU students -- graduate or undergraduate -- who are interested in gaining research experience in the Browder Research Group are encouraged to discuss research opportunities with Dr. Browder. Prerequisites for joining the Browder Group include successful completion of CHM 235 and CHM 235L (or equivalent), and completion of CHM 238 and CHM 238L is preferred.