Jesse Ondersma

 

Progress Towards the Synthesis of Apomorphine

Recently a thyroid hormone metabolite, T1AM, was found which activates a rat trace amine-associated receptor (rTAAR1) and induced rapid physiological responses in mice, such as: reduced cardiac output, reduced metabolism, and hypothermia. R()apomorphine has been shown to elicit the same rapid activation of  rTAAR1. S(+)apomorphine, however, shows very little if any activation of rTAAR1. Our objective is to develop an enantioselective synthesis of apomorphine which can be modified to synthesize analogs to explore the molecular basis of apomorphine induced rTAAR1 activation. To this end, we have been synthesizing the two key fragments in a novel synthetic route to apomorphine. For the synthesis of the first fragment we have explored the protection and iodination of a catechol. For the synthesis of the second fragment we have explored the formation of a lactam by a series of reactions. Upon completion of our synthetic apomorphine it will be compared with the commercially available product. Both enantiomers will be measured for rTAAR1 activation to determine the EC50 of each and to determine if the (S) enantiomer is an antagonist of rTAAR1.

Faculty Mentor: Matthew E. Hart

Page last modified July 14, 2009