University of Wisconsin - La Crosse
Subject Listing - Chemistry
Advisor: Dr. Aaron Monte
Friday, Oral Session 5, Presentation 4, Karpen Hall 038
SYNTHESIS OF SELECTIVE SEROTONIN 5-HT2A AND 5-HT2C RECEPTOR AGONIST
Serotonin (5-hydroxytryptamine, 5-HT), a major neurotransmitter of the central nervous system, is involved in a wide range of neuronal processes. Some of these include the regulation of mood, sleep cycles, awareness/consciousness, and memory. To initiate specific responses, serotonin typically binds to an appropriate 5-HT receptor population and initiates a chain of biochemical events that alters the brain`s physiology in some way. The 5-HT2 receptor is one type of 5-HT receptor and consists of at least three distinct subclasses, 5-HT2A, 5-HT2B, and 5-HT2C. In previous work in this laboratory, a serotonin agonist was prepared that showed high affinity for 5-HT2A/2C receptors but did not show selectivity for either one of the two. We present here the synthesis of two new agonist ligands that may have differential affinities for the 5-HT2A or 5-HT2C receptor subtypes. The eight-step synthesis was begun with commercially available para-methoxyphenol, which was modified by introducing bromoethyl and bromopropyl groups to the aromatic oxygen atoms. A tandem ring closure using n-butyllithium was then performed to create the key tricyclic intermediate. Formylation of this asymmetric intermediate gave two regioisomers, which were separated chromatographically and carried through a parallel sequence allowing final elaboration of the desired alkylamine sidechains. Subsequent pharmacological analysis of the two target molecules will provide a more detailed depiction of the 5-HT2A/2C agonist binding site.
Advisor: Dr. Aaron Monte, Professor and Chair, Department of Chemistry, University of Wisconsin - La Crosse, La Crosse, WI