The goal of this project was to synthesize and test novel TAAR regulators. Various aminoindane derivatives in the literature have been shown to be potent agonists or antagonists for the TAAR receptor. By testing different, but similar structures more potent agonists and antagonists could be uncovered. This, in turn, would allow more thorough research of the biological activities involved with the receptor. Developing these compounds could therefore lead to advancements in the treatment of patients with thyroid hormone related diseases. The following work in progress reports the synthesis and trouble shooting involved for the formation of novel indane derivatives and their subsequent regulatory behaviors with the TAAR-1 receptor. 5-Hydroxy-1-indanone underwent a copper coupling reaction with 6 equivalents of phenyl boronic acid to produce 5-phenoxy-1-indanone (72% yield). A grignard addition-elimination sequence gave (Z)-5-phenoxy-1-phenylindene (69.7% yield) using phenyl-magnesium-bromide and p-Toluene-Sulfonic Acid An attempt was made to do a hydroboration with sodium borohydride and boron tri-fluoride followed by an amination with 1.25 equivalents hydroxyl-amine-O-sulfonic acid to give the desired aminoindane, however analysis of the reaction via 1HNMR, GC/MS and IR shows that an oxidation and not an amination occurred at the 1,2 carbon-carbon double bond. Repeated trials of the reaction show the same result. An alternative route was attempted via a mesylation of the alcohol group in order to allow a subsequent SN2 substitution with sodium azide, however all reaction conditions have shown negligible, if any, mesylation activity. In order for the regulatory behaviors of the compound to be examined, a suitable synthesis of the desired amines needs to be discovered.
Faculty Mentor: Matthew Hart, Chemistry
Kevin presented at the 237th ACS National Meeting and Exposition March 21-26, 2009 in Salt Lake City, UT