Browsing by Author "Hitchens, Jake R."

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    Aminolytic Cleavage from Wang Resin. A New Distributed Drug Discovery Laboratory for the Undergraduate Curriculum
    (Office of the Vice Chancellor for Research, 2016-04-08) Scott, William L.; Burris, Sarah D.; Hitchens, Jake R.; Samaritoni, J. Geno; O’Donnell, Martin J.
    When treated with ammonia or methylamine, unnatural amino acids bound to Wang resin (1) are released as their corresponding amides 2 in good yield and purity. When carried out at room temperature, aminolytic cleavage proceeds slowly with a four-day exposure to ammonia in methanol representing an optimal reaction time. Aminolytic cleavage proceeds well with unhindered primary amines, however, the hindered amine isopropylamine and benzylamines are unacceptably slow to effect cleavage. Use of the secondary amine pyrrolidine led to a complex mixture. Due to the large stoichiometric amine excess required, the scope is currently limited to unhindered, volatile, primary amines. The overall synthesis of 2 from BPI-Gly-Wang resin represents a new Distributed Drug Discovery Laboratory (D3-7) and was rolled out to the spring 2016 Organic II laboratory.
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    The Synthesis and Biological Activity of N-Acylated Amino Acids. A Collaborative Effort of Distributed Drug Discovery (D3)
    (Office of the Vice Chancellor for Research, 2016-04-08) Scott, William L.; Popiołek, Łukasz; Biernasiuk, Anna; Hitchens, Jake R.; Samaritoni, J. Geno; O’Donnell, Martin J.
    As part of a Distributed Drug Discovery collaborative effort between students at IUPUI and Medical University of Lublin (Poland), the solid-phase combinatorial synthesis of a series of natural, acylated tyrosine (1) and phenylalanine (2) analogs was carried out in replicated fashion. The crude samples were purified and characterized by LC/MS, proton NMR, and in cases involving novel structures, by proton and carbon-13 NMR and high-resolution mass spectrometry. The samples were characterized in biological assays at the Medical University of Lublin against the Gram-positive bacteria Staphylococcus aureus ATCC 25923, Staphylococcus epidermidis ATCC 12228, Bacillus cereus ATCC 10876, Bacillus subtilis ATCC 10876, and Micrococcus luteus ATCC 10240. Although activity of the 2-nitro and 3-nitro derivatives of phenylalanine was not reproduced by the IUPUI samples, the 5-chlorosalicylic acid derivative 1g demonstrated good activity against M. luteus (MIC = 62.5 g/mL) and moderate activity against S. aureus, S. epidermidis, and B. cereus. O Cl OH HN OH OH O O Ar HN X OH O 1 X = OH 2 X = H 1g