The monoamine neurotransmitter dopamine (DA) has an important role in the pharmaceutical industry. DA plays key roles in locomotion, cognition, and addiction. Further understanding of these neurotransmitters could lead to countless discoveries. Our research focuses on the D1-like family of DA receptors, which have been implicated in memory formation. Further investigation into the pharmacological effects of D1-selective agonists could lead to treatments for people with cognitive deficits.<br/>The compound 5-phenyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[h]isoquinoline-7,8- diol, synthesized as a racemic mixture previously, was noted to be a high-affinity D1-like receptor-selective agonist. Due to the fact that one enantiomer may have a higher affinity or greater potency than the other, greater insight into the activity of this compound may be found by synthesizing and separating the enantiomers.<br/>The first step in the reaction is a Perkin transformation, which belongs in the class of aldol-like condensation reactions. The alkene is catalytically reduced in an atmosphere of hydrogen. The acid is reduced to the alcohol, which is then converted to a better leaving group in order to undergo an SN2 reaction with a cyanide ion. The nitrile is hydrolyzed and an intramolecular Friedel-Crafts reaction forms the tetralone ring. A Michael reaction between the unsaturated nitrile and the lithiated oxazoline is used to add two additional carbon atoms, though a malonic ester synthesis also has been considered. Additional progress is underway to complete the isoquinoline scaffold and form diastereomeric amides with an enantiopure carboxylic acid, which will hopefully be separable by crystallization or chromatography.<br/>Once fully synthesized and separated, each enantiomer will be evaluated in cellular systems for affinity and potency at various brain receptors. These chemical tools will be used to shed light on binding in the dopamine receptor in efforts to improve DA-selective drug design.

Toward the enantiomeric resolution of an extremely potent and selective D1 dopamine receptor agonist

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