new functional groups. (3) Developing novel routes for functionalizing readily available organic building blocks DEPARTMENT OF CHEMISTRY such as alkenes and alkynes. (4) Exploring the reduc- tive coupling of aldehydes and alkynes or enones and alkynes. Recent studies have demonstrated strategies involving redox isomerization to avoid the use of reduc- Graduate Program ing agents in processes of this type. (5) The discovery of new glycosylation methods and their application in collaborative projects involving enzymatic C-H oxida- tion reactions.

Traditional Synthetic Novel C–H Bond Approach Functionalization Approach Fluorinated amino acids can be used to make super-stable “Tef- O O N O NH N lon” proteins; here the interior of a small protein is packed with the Michigan offers a diverse selection of research oppor- 2 Br 1. Br cat. PdII fluorous amino acid hexafluoroleucine (Marsh). O N tunities in Organic Chemistry with particular strengths Y Y Y N 2. NH3/MeOH Oxidant–X in Organometallic Chemistry, Organic Synthesis, Bioor- X X H 3. CH3I ganic Chemistry, and Organic Materials. Our innovative treatment of autoimmune diseases and cancer. (3) Anti-anxiety research rotation program allows students to explore Anti-convulsant Developing and applying chemical tools to study a range of exciting possibilities before choosing an Palladium-catalyzed C-H functionalization of an arene (Sanford). the role of oxidants as signaling molecules and the advisor. Specific research projects in each area are biological basis of aging. (4) Elucidating catalytic highlighted below. mechanisms and essential active site features of me- talloenzymes and ribozymes, including protein farnes- Organic Synthesis yltransferase, UDP-3-O-acyl-GlcNAC deacetylase, his- R3 H tone deacetylase and ribonuclease P. These studies O Ni(0) O R2 Designing efficient synthetic routes to complex organic + should enhance our ability to design potent inhibitors + O R2 R3 molecules remains a challenge. At Michigan, several H R4 R of these enzymes useful for the treatment of cancer 1 R1 O R4 research groups are working on total syntheses using or bacterial infections. (5) Exploring the interface methods developed in their labs. Recent synthetic Nickel-catalyzed coupling of an aldehyde, alkyne and enone via redox between biological macromolecules and materials isomerization (Montgomery). targets include aigialomycin D, cephalotaxine, and chemistry through the de-novo design of extensively aphanorphine. fluorinated “Teflon” proteins. Such proteins exhibit useful new properties such as increased thermal sta- Organometallic Chemistry OH O CH 3 bility, resistance to unfolding in organic solvents, and Transition-metal mediated bond formation can be a O O resistance to degradation by proteases. versatile and efficient transformation in any organic N H HO O synthesis. At Michigan, several research groups are fo- N Me OH HO cused on the use of transition metals in reaction discov- HO OH Me ery, synthetic methodology development, mechanistic OMe aigialomycin D Cephalotaxine Aphanorphine chemistry, and complex molecule synthesis. Highlights of ongoing research projects include: (1) Developing new transition-metal catalyzed reactions for the ste- Bioorganic Chemistry reoselective synthesis of saturated heterocycles such as tetrahydrofurans and pyrrolidines. (2) Discovering Research efforts in Bioorganic Chemistry at Michigan methods to transform inert carbon-hydrogen bonds into focuses on applying chemical principles, particularly those of organic chemistry, to solve problems in human health. Highlights of ongoing research projects include: (1) Developing strategies for reprogramming gene ex- O O Br cat. Pd2(dba)3 pression using small molecules, both natural products and cat. dppb N NH Ph ‘designer’ molecules. These molecules are being used Ph + NaOtBu, Toluene N 105 °C as mechanistic probes of eukaryotic transcription as well 82% yield N as prototypes for transcription-targeted therapeutics for Detecting redox-regulated proteins in living cells. (A) Sulfenic acid >20:1 dr post-translational modifications are selectively detected via the diseases ranging from diabetes to cancer. (2) Identify- cell-permeable probe DAz-1. (B) Visualization of protein sulfenic Palladium-catalyzed reaction of an γg-amino olefin and an aryl ing novel molecular targets and small molecules for the acids in MEF cells treated with DAz-1 (right) or untreated (left) bromide (Wolfe). (Carroll). Organic Chemistry

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at the www.umich.edu/~michchem/ Michigan University Chemistry 2008 734-647-4865 [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] www.umich.edu/~michchem [email protected] toll free 888-999-2436 or 734-764-7278 toll free cover: Highlights of research in Organic Chemistry at cover: Highlights of research Michigan. Gary Glick Masato Koreeda Anna Mapp Neil Marsh Adam J. Matzger Anne McNeil John Montgomery Melanie Sanford David Sherman Edwin Vedejs Wolfe John P. Ronald Woodard Website: Email: Phone: Fax: Further Information For more information about specific research interests, go to: www.umich.edu/~michchem. Please feel free to contact faculty directly: Kate S. Carroll Brian Coppola Fierke Carol How to Apply Application to the Chemistrythe University of Michigan Graduateis online at www.umich.edu/ Program ~michchem/graduate/ at admission, see www.umich. For questions regarding by edu/~michchem or contact the department Life in Ann Arbor in Ann Life The University of Michigan offers a rich intellectual envi- ronment. Opportunities for research and collaboration in Organic Chemistry are enhanced by top-ranked - pro grams in Medicinal Chemistry, Biochemistry, and the Life Institute. Sciences 110,000, of city small a Arbor, Ann in located is University The with town college a of charm and comfort the combining of a largethe vivid cultural life city. n S S 9 1 H 9 C S S S S 9 1 H 9 C S S n S S S Optical microscope image of a novel small- Optical microscope (McNeil). molecule based hydrogel S 9 S 1 H 9 S C S S S 9 S 1 H 9 S C Organic Materials research at Michigan is focused focused is Michigan at research Materials Organic synthetic through properties functional creating on modifications to polymers and small-molecules. Highlights of ongoing research projects include: (1) Developing techniques to control the process of crystallization using organic polymers as phase im- with materials making of goal the with directors chemistry materials Combinatorial function. proved nov- Developing (2) efforts. these in role vital a plays el routes for the efficientproduction of new mem- bers of conjugated oligomers and polymers with oligothio- fused as such constraints, structural planar phenes, and their studying behavior in state solid the as it relates to important appli- device cations such as organic tran- film thin (OTFTs). sistors These - struc ture types also find ap- plication in the construction of porous solids for applications ranging from gas storage to . (3) Design- ing new molecules that induce hydrogelation in the presence of an analyte for use in chemical and biological sensing. (4) Developing living po- con- new of synthesis the for methods lymerization jugated polymer architectures for optoelectronic applications. Organic Materials Methodology development for the synthesis of conjugated polymers and oligomers of fused-ring thiophene compounds (Matzger).