Exploratory study of ionophoric spiroethers and spioketals
Bipolar disorder, also known as manic-depressive illness, is a brain disorder that can be treated successfully with lithium salts. Lithium ionophores can be used to construct a Li+ ion selective electrode, which can in turn be used for effective monitoring of lithium levels in blood. Lithium ionophores synthesized previously in the group form insoluble complexes upon complexation. Consequently, two new molecules were designed to enhance the solubility of the complexes formed with lithium. Methods to synthesize these compounds have been explored and described. The area of biphasic complexation has also been explored by synthesizing compounds with alkoxyethyl side chains as ligating sites for metal ions. Desired compounds were synthesized starting from inositol in short and efficient routes. Complexation studies were performed in the solution phase and gas phase using picrate extraction studies and mass spec, respectively. En route to the synthesis of spiroether lithium ionophores cyclohexanone intermediates with spiroether units in the alpha and beta position were found to equilibrate. Corresponding cyclopentanones were also found to exhibit this behavior. Influence of ring size of the equilibrium was investigated by synthesizing cyclopentanones containing a combination of five and six membered spiroether functionality. Oxonium ion-initiated pinacolic ring expansion reaction has been previously reported by our group. This discovery takes advantage of the fact that ketone adducts of metalated vinyl ethers are amenable to conversion to oxonium ions under acid-catalyzed conditions. This results in a diastereoselective ring expansion and spiroketone formation. Our next advance into spirocyclic chemistry involves application of pinacolic ring expansion methodology in the synthesis of 1,6-dioxaspiro[4.5]decane frameworks. Subsequent transformations result in the conversion of spiroketones formed to spiroketal frameworks. Efforts were made to apply the pinacol ring expansion methodology in the synthesis of AL-2 and lissoketal. With an efficient synthesis of 6.19 in hand, attention was focused on alkylation at C3 position. However, alkylation was thwarted. The final approach has given rise to a strategy that involves construction of the unsaturated pyran ring from known spiroketal 6.26 and has allowed for the synthesis of Olefin 6.31. With Olefin 6.31 in hand, synthesis of lissoketal might be realized through more transformations.
School:The Ohio State University
School Location:USA - Ohio
Source Type:Master's Thesis
Keywords:ionophores spiroketals spiroethers
Date of Publication:01/01/2006