Abstract

Many people are diagnosed with thyroid related disorders, and many more are unaware of their existing thyroid problems. T1AM, a naturally occurring metabolite of the thyroid hormone (TH), has been shown to activate the Trace Amine Associated Receptor 1 (TAAR1) and exhibits effects that oppose those of the TH. It is, therefore, likely that there is regulatory relationship between T1AM and the TH. In order to better understand this relationship, a compound must be developed that will effectively block TAAR1. Previously our lab has examined the two different mirror images of apomorphine. One of the mirror images inhibited and the other activated TAAR1. The project described herein, is targeted toward the synthesis of a truncated ergoline, which is structurally similar to both T1AM and apomorphine. Only one mirror image is present in the naturally occurring form of ergolines, and they are known to be activators of TAAR1. To determine if the non-natural mirror image is an effective inhibitor, it is essential that an efficient synthesis be developed that will allow for the formation of both mirror images of the truncated ergoline. Several steps have been optimized using the desired system, and several other steps have been optimized using a model system. Currently the key step for the completion of the truncated ergoline is being examined using data collected from the model system.