Browsing by Subject "Distributed Drug Discovery"

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    Saponification of N-Acylated L-Phenylalanine Wang and Merrifield Resins. Assessment of Cleavage Efficiency and Epimerization
    (Office of the Vice Chancellor for Research, 2013-04-05) Carnahan, Jon M.; O'Donnell, Martin J. O.; Samaritoni, J. Geno; Crews, DeMarcus K.; Lawrence, Brian M.; Scott, William L.
    As part of a continuing effort to modify Distributed Drug Discovery (D3) synthetic procedures to enhance safety and accommodate the limited resources available to students in developing-world countries, we have recently begun to examine alternatives to trifluoroacetic acid (TFA)-cleavage of amino acid derivatives from polystyrene-based resins. Cleavage of a representative example, N-(4-chlorobenzoyl)-L-phenylalanine, from both Wang and Merrifield resins was accomplished in thirty minutes at room temperature using 0.5M sodium hydroxide in methanol/tetrahydrofuran. In a side-by-side comparison with cleavage using TFA, results indicated that saponification from Wang resin was incomplete after thirty minutes. Experiments designed to examine separately the effect of reaction time, temperature, and concentration were performed and results will be presented. Additionally, investigations were performed to assess the degree of epimerization which had occurred during cleavage of Merrifield-bound L-phenylalanine acylated with both (R)- and (S)-mandelic acid. Results revealed a small but significant amount of epimerization (15:1 to 31:1 diastereomeric ratios) after a thirty-minute cleavage time at room temperature.
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    Solid-Phase Synthesis of Arylpiperazine Derivatives and Implementation of the Distributed Drug Discovery (D3) Project in the Search for CNS Agents
    (MDPI, 2011-05-19) Zajdel, Paweł; Król, Joanna; Grychowska, Katarzyna; Pawłowski, Maciej; Subra, Gilles; Nomezine, Gaël; Martinez, Jean; Satała, Grzegorz; Bojarski, Andrzej J.; Zhou, Ziniu; O’Donnell, Martin J.; Scott, William L.; Chemistry and Chemical Biology, School of Science
    We have successfully implemented the concept of Distributed Drug Discovery (D3) in the search for CNS agents. Herein, we demonstrate, for the first time, student engagement from different sites around the globe in the development of new biologically active compounds. As an outcome we have synthesized a 24-membered library of arylpiperazine derivatives targeted to 5-HT1A and 5-HT2A receptors. The synthesis was simultaneously performed on BAL-MBHA-PS resin in Poland and the United States, and on BAL-PS-SynPhase Lanterns in France. The D3 project strategy opens the possibility of obtaining potent 5-HT1A/5-HT2A agents in a distributed fashion. While the biological testing is still centralized, this combination of distributed synthesis with screening will enable a D3 network of students world-wide to participate, as part of their education, in the synthesis and testing of this class of biologically active compounds.