Scholarship of Discovery
Pharmacologic intervention with stereochemical probes allows for the treatment of medical conditions by affecting receptors in the body and causing receptors to respond to the presence of the probe. Novel cyclopropyl derivatives were synthesized could serve as a stereochemically rigid probes of certain pharmacological receptors and could have potential use as a drug. A probe is a molecule or ligand that can bind to and interact with a receptor in the human body. This interaction triggers a desirable response by increasing or decreasing the presence of a compound (e.g. dopamine for depression) in order to repair a chemical imbalance in the system. Cyclopropyl rings are a structure commonly found in drugs due to their strengthening effects on activity. (Wilson, Beale, & Block, 2011). These cyclopropyl rings found in drugs, including those for anti-depressants, cytochrome P450 inhibitors, and as 5-HT receptor ligands (Christmas, Coulson, Maxwell, & Riddell, 1972), (Vanveravong, Kanthasamy, Lucaites, Nelson, & Nichols, 1998), (Ortiz de Montellano, Correia, 1983). This experiment begins by forming an alkene, then uses the Simmons-Smith reaction to create a cyclopropyl ring with three other substituents: an amino group, an acetoxy group, and a phenyl group. Here we attempt to form the cyclopropyl probes using a series of three reactions. The first reaction forms an alkane that can then by transformed into an alkene with the desire substituents. The Simmons-Smith reaction is then used to transform the alkene into the cyclopropyl ring. The first two reactions in the series were completed and IR spectra suggest that the desired products were synthesized. The next phase of the synthesis would begin with the Simmons-Smith reaction to form the cyclopropyl derivatives, these derivatives should be diastereomers of the desired cyclopropyl ring. The compound may be of use as an antidepressant, antihistamine, and analgesic because of this cyclopropyl structure (Wilson, Beale, & Block, 2011). Upon synthesis, these diastereomers will be tested for pharmacologic activity at the 5-HT receptor and use as an anti-depressant. The diastereomers will also be tested to see if they interfere with cytochrome P450 and drug metabolism.
Hohn, Grace, "Synthesis, Including Microwave Promotion, of Selected Cyclopropyl Derivatives as Stereochemically Rigid Probes of Certain Pharmalogical Receptors" (2017). Honors Program Projects. 65.