Michael D. Mosher, Ph.D., Dipl.Brew.
Chair and Professor
Department of Chemistry and Biochemistry
Director, Brewing Lab Science Program
University of Northern Colorado
Greeley, CO 80639
Office: (970) 351-2559
Fax: (970) 351-2533
Novel Routes to 2-Isoxazolines and Related Heterocycles
ISO-1, an inhibitor of the proinflammatory cytokine MIF, has been shown to exhibit preventative properties toward Type 1 Diabetes in transgenic mice. We have shown that this compound, and derivatives, can be prepared by the intra-molecular cyclization of a beta,gamma-unsaturated oxime. The reaction utilizes a palladium(II) catalyst to effect the cyclization, and depending upon the specific ligands employed, can result in modest stereocontrol of the reaction.
Recent studies in our laboratory have shown that palladium(0) can mediate a tandem intra-molecular cyclization / aryl coupling. The reaction involves the cyclization of a beta,gamma-unsaturated oxime in the presence of a substituted arene. Yields for the reaction are variable and dependent upon the electronic effects of the substituents.
In other work, our group is exploring the intercalative properties of O-substituted N-acridinyl hydroxylamines. These compounds are prepared by coupling the O-substituted hydroxylamine with 9-chloroacridine. The results of an initial study indicate that these compounds are effective DNA intercalators that also express some biological activity (as measured by MTT assay). Further work in this area will involve exploration of the kinetics of hydrolysis of these compounds, evaluation of the specific interactions during intercalation, and modification of the O-substituted compounds to enhance biological activity. priately substituted alkene. While this method for isoxazoline synthesis can be useful, regiochemical and stereochemical concerns limit the utility of the method in some cases.
In addition to our work with heterocyclic chemistry, we have begun exploring two major areas of research in beer brewing. The first of these projects involves the exploration of the mechanism of hop acid isomerization. Initial work in this area indicates that the isomerization is likely catalyzed by compounds existing within the hop oil or wort. The goal of the project is to confirm the first order reaction kinetics and to illucidate the details of the mechanism of the reaction. The second of the projects involves the use of spectroscopic techniques for the analysis of components in beer. For example, we have shown that %ABV can be rapidly analyzed by using ATR. We are currently exploring beer as an analyte for chemoinformatic analysis.
- Mosher, M.D.; Branan, D.; Kelter, P.B., Chemistry - The Practical Science, 2nd Edition, Roberts Publishing, Denver, CO, USA; ~1200 pp. (24 chapters) in preparation with planned BBD 2016 Fall
- “Potential DNA bis-Intercalating Agents. Synthesis and Antitumor Activity of N,N'-(Methylenedi-4,1-cyclohexanediyl-bis(9-acridinamine) Isomers”, Gribble, G.W.; Mosher, M.D.; Jaycox, G.D.; Cory, M.; Fairley, T.A. Heterocycles, 2014, 88(1), 535-546. doi: 10.3987/COM-13-S(S)77
- “Podcasting in Organic Chemistry”, Mosher, M.D., in “Advances in Teaching Organic Chemistry”, Duffy-Matzner, J., Pacheco, K. Eds., ACS Symposium Series; American Chemical Society: Washington, DC, 2012, 1108, 225-231. doi: 10.1021/bk-2012-1108.ch014
- “Non-cyclization routes to 2-Isoxazolines and 2-Isoxazoline N-oxides”, Mosher, M.D. Curr. Org. Syn., 2011, 8(5), 645-658.
- “Organic Mastery: an activity for the undergraduate classroom”, Mosher, M.D.; Mosher, M.W.; Garoutte, M. J. Chem. Educ., 2012, 89(5), 646-648. doi:10.1021/ed200015v
- “5-Bromomethyl-4,5-dihydroisoxazoles”, Mosher, M.D.; Norman, A.L.; Shurrush, K.A. Tetrahedron Lett., 2009, 50, 5647-5648. doi:10.1016/j.tetlet.2009.07.106
- “Bis-anthracenyl Isoxazolyl Amides have Enhanced Anticancer Activity”, Gajewski, M.; Beall, H.; Schnieder, M.; Stranahan, S.M.; Mosher, M.D.; Rider, K.C.; Natale, N.R. Bioorg. Med. Chem. Lett., 2009, 19, 4067-4069; doi:10.1016/j.bmcl.2009.06.019
- “Design, Synthesis and Biological Evaluation of a Novel Class of Anticancer Agents: Anthracenylisoxazole Lexitropsin Conjugates”, Han, X.; Li, C.; Mosher, M.D.; Rider, K.C.; Zhou, P.; Crawford, R.L.; Fusco, W.; Paszczynski, A.; Natale, N.R. J. Bioorg. Med. Chem., 2009, 17, 1671-1680; doi:10.1016/j.bmc.2008.12.056