ORGN 128 |
| The use of substituted cyclopropane scaffolds to study neurotransmitter modulators has highlighted a need for the rapid conversion of cyclopropane carboxaldehydes into a variety of substituted amines by reductive amination. We have established a procedure for parallel processing of these reactions using solid-supported ammonium cyanoborohydride and employing an amine-scavenger resin to facilitate product purification. Thus both enantiomers of a range of aldehydes were converted into the corresponding 1°, 2° and 3° amines by reaction with ammonium chloride, methylamine and dimethylamine or morpholine respectively. In this initial library, isolated yields of pure amines were 10-60% without chromatographic purification. The 1° amines were typically isolated in reduced yields due to the formation of significant amounts of double alkylation products and work is continuing to improve efficiency in the preparation of 1° amines. Initial biological data for these compounds indicate that they exhibit promising selectively for serotonin transporter sites over dopamine and norepinephrine, suggesting potential future applications as SSRI's. The parallel synthesis of this library of compounds as well as their exciting biological activity will be discussed.
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Asymmetric Reactions and Syntheses, Physical Organic Chemistry, Combinatorial Chemistry, Total Synthesis
8:00 PM-10:00 PM, Sunday, 26 March 2006 Georgia World Congress Center -- Ex. Hall B4, Poster
Division of Organic Chemistry |
