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Professor of ChemistryProfessor of
Primary Office: E531 CBIowa City, IA 52242
Primary Office Phone: 319-335-1365
Email: email@example.comWeb: More About Dr. Wiemer - Related Websites and Resources
BS, Chemistry, Marquette UniversityPhD, Organic Chemistry, University of Illinois, UrbanaPhD, Organic Chemistry, University of Illinois-Urbana
Post Doctorate, Organic Chemistry, Cornell University
Biosciences Graduate Program
Our research interests include development of new strategies for organic synthesis based on organophosphorus compounds, design and synthesis of various ãunnaturalä compounds as metabolic probes or antimetabolites, and synthesis of biologically active natural products.
The natural products we target are primarily terpenoids or compounds that contain significant terpenoid portions. Past goals included the diterpenoid (+)-jatrophone (1) of interest as a potential anti-cancer agent, and the sesquiterpenoids arenarol (2) and avarol which were of interest as potential anti-HIV agents. Current targets include cylindrol A (3) and related inhibitors of farnesyl:protein transferase, prenylated benzoic acids that we have isolated from tropical plants as potential anti-insect and anti-fungal agents, and the schweinfurthins
Total synthesis of such complicated targets often requires development of new approaches to the formation of a particular substructure. This is part of the challenge, and the opportunity, of this research. A major focus of our efforts has been development of new methods for formation of carbon-phosphorus bonds and new applications of organophosphorus compounds in organic synthesis. For example, we have explored use of electrophilic phosphorus reagents for preparation of b-keto phosphonates. While b-keto phosphonates are synthetic intermediates of great value, especially in the Horner-Wadsworth-Emmons (HWE) condensation, applications of these compounds have been restricted due to the difficulty of preparing some classes. We have discovered a route to cyclic §-keto phosphonates via rearrangement of cyclic vinyl phosphates, and developed a general method for preparing b-keto phosphonates through reaction of enolates with P(III) halides. These methodologies lead to new strategies for facile assembly of complex molecules, and often become key parts of our total syntheses. They also have allowed preparation of complex nucleoside and carbohydrate derivatives of interest for their potential biological activity.
Our interests in terpenoid synthesis and organophosphorus chemistry have combined to generate an investigation of terpene metabolism. In collaboration with Prof. Raymond J. Hohl, UI Departments of Internal Medicine and Pharmacology, we have designed several families of terpenoid phosphonates as analogues of farnesyl pyrophosphate (FPP). FPP serves as both a key metabolic intermediate in steroid biosynthesis and as a metabolic reagent for addition of lipophilic terpenoid units to a variety of proteins. For example, farnesylation of RAS proteins is a critical step in the posttranslational processing that results in their membrane association. Because RAS proteins must become membrane bound to serve as signaling proteins and regulate cell proliferation, the farnesylation step has been identified as a promising target for development of potential anti-cancer agents. Through synthesis and bioassay of farnesyl pyrophosphate analogues, we hope to clarify their value as potential anti-cancer agents, and learn how to redirect protein posttranslational processing.
Date Last Modified: 06/07/2014 -
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