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JCE Featured Molecules
William F. Coleman
Molecular Models of Pharmaceuticals
Wellesley College Wellesley, MA 02481
Cholera Drugs and a Cough Suppressant April 2009 Featured Molecules This month we feature molecules from two papers that deal with aspects of medicinal chemistry. Chriss McDonald gives us a straightforward synthesis of the new cholera drug virstatin (1) and Todd Hamilton and Frank Wiseman describe an analysis of the familiar cough suppressant dextromethorphan (2). We also include structures of several other substances used in treating cholera and other diseases characterized by virulent diarrhea— tetracycline, nitazoxanide, ciprofloxacin, and a structure of the backbone of the fluoroquinolones—as well as the starting material in the virstatin synthesis. The virstatin structure demonstrates once again the importance of having three-dimensional structures available for students to examine. In the supplementary material for ref 1 it is mentioned that the interpretation of the 1H NMR spectrum of
the molecule is simplified by the presence of a plane of symmetry that bisects the molecule. It is difficult to convey that symmetry in a two-dimensional structure, and without access to the threedimensional form students might either miss seeing the plane, or think, despite the use of the word bisect, that the plane is in the plane of the rings. Looking at the three-dimensional structure, and rotating it, leaves no question about the location of the symmetry plane, or that the point group is Cs. Naphthalimide and its conjugate base present students with the opportunity to perform quite high-level computations relatively quickly and to use computed charges to probe the charge delocalization in the conjugate base, delocalization that leads, as is pointed out in ref 1, to the imide proton having an acidity similar to that of hypochlorous acid. All of these molecules suggest two activities that perhaps should be more prevalent in the chemistry curriculum: calculation of the atom efficiency or atom economy of the synthetic routes to the drugs and a life cycle analysis of the materials. In the case of virstatin, students might explore the origin of the naphthalimide that is used as a starting material and the economy of its production leading up to their synthesis. For the other species students could find synthetic routes in the literature and see whether such analyses have been performed, and whether alternative routes might be more atom efficient. These activities provide a needed balance to computation of percent yield of the desired product. Literature Cited
Virstatin is of significant interest because of its ability to inhibit the disease cholera by a unique mode of action (1).
1. McDonald, C. E. J. Chem. Educ. 2009, 86, 482–483. 2. Hamilton, T. M.; Wiseman, F. L. Jr. J. Chem. Educ. 2009, 86, 479–481.
Supporting JCE Online Material
http://www.jce.divched.org/Journal/Issues/2009/Apr/abs528.html Full text (HTML and PDF) with images in color Links to cited JCE articles Supplement Find “Molecular Models of Pharmaceuticals: Cholera Drugs and a Cough Suppressant” in the JCE Digital Library at http ://www.JCE .DivCHED.org/JCEWWW/Features/ MonthlyMolecules/2009/Apr/ Dextromethorphan is commonly used as an antitussive, or cough suppressant. Unlike codeine (the most commonly used narcotic cough suppressant), dextromethorphan is available over-the-counter (2).
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The molecules added to the collection this month are: ciprofloxacin dextromethorphan fluoroquinolone backbone naphthalimide naphthalimide conjugate base nitazoxanide tetracycline virstatin
Journal of Chemical Education • Vol. 86 No. 4 April 2009 • www.JCE.DivCHED.org • © Division of Chemical Education
