Research in our group focuses on the use of organic molecules as asymmetric catalysts. We explore the mechanisms of organocatalytic reactions, develop their synthetic potential, and use them as key steps in the synthesis of complex, biologically active natural products.
Cinchona alkaloids have served as our primary scaffold for the development of asymmetric organocatalysts. These alkaloids, exemplified by quinine, are readily available, stable, non-toxic, and easily modified. We have developed cinchona alkaloid analogs that function
as highly asymmetric catalysts for nucleophile and electrophile catalyzed reactions. For example, silyl cinchona alkaloids are excellent enantioselective catalysts for the dimerization of ketenes, a reaction that proceeds via nucleophilic catalysis to form an acylammonium enolate intermediate. Other cinchona alkaloid derivatives serve to catalyze the Feist-Bénary reaction, this time by way of a hydrogen-bonded intermediate. We are also developing nucleophile-catalyzed reactions of acyl ammonium enolates with alternative electrophiles, and alternative hydrogen-bond accelerated reactions.
After
we develop a catalytic, asymmetric reactions, we apply them to the synthesis of complex molecules. One such project involves the use of the ketene dimerization reaction in the synthesis of members of the polyketide family of natural products, such as the aplyronines. The polyketides generally have challenging structures and interesting biological activities. We are also using the Feist-Bénary reaction in the synthesis of diresorcylaldehyde natural products such as the vestinones. These compounds display a wide variety of interesting biological activities, most likely stemming from their ability to inhibit cAMP-dependent protein kinases.
Selected Publications:
Huang, Y.; Calter, M.A.* “Catalytic asymmetric synthesis of a-phenoxy-b-aryl-b-lactams,” Tetrahedron Lett. 2007, 48, 1657-1659
Calter, M.A., *; Phillips, R.M.; Flaschenrien, C. “Catalytic Asymmetric, “Interrupted” Feist-Bénary Reactions,” J. Am. Chem. Soc. 2005, 127, 14566-14567.
Calter, M.A., Tretyak, O.A., et al., “Formation of disubstituted beta-lactones using bifunctional catalysis,” Organic Letters 2005, 7, 1809-1812
Calter, M.A., Song, W., et al., “Catalytic asymmetric synthesis and diastereoselective aldol reactions of dipropionate equivalents,” Journal of Organic Chemistry 2004, 69, 1270-1275.
Calter, M.A. and Zhou, J.G., “Synthesis of the C-1-C-27 portion of the aplyronines,” Tetrahedron Letters 2004, 45, 4847-4850.
Calter, M. A.; Orr, R. K.; Song, W. “Catalytic, Asymmetric Preparation of Ketene Dimers from Acid,” Chlorides. Org. Lett. 2003, 5, 4745-4748.
Calter, M. A.; Liao, W. “First Total Synthesis of a Natural Product Containing a Chiral, beta-Diketone: Synthesis and Stereochemical Reassignment of Siphonarienedione and Siphonarienolone,” J. Am. Chem. Soc. 2002, 124, 13127-13129.
Calter, M. A.; Guo, X. “Synthesis of the C21-C34-segment of the aplyronines using the dimer of methylketene,” Tetrahedron 2002, 58, 7093-7100.
Calter, M. A.; Zhu, C.; Lachicotte, R. J. “Rapid Synthesis of the 7-Deoxy Zaragozic Acid Core,” Org. Lett. 2002, 4, 209-212.
Calter, M. A; Zhu, C. “The Scope and Diastereoselectivity of the “Interrupted” Feist-Bénary Reaction,” Org. Lett. 2002, 4, 205-208.
Calter, M. A.; Liao, W.; Struss, J. A. “Catalytic, Asymmetric Synthesis of Siphonarienal,” J. Org. Chem. 2001, 66, 7500-7504.
Calter, M. A.; Guo, X.; Liao, W. “One-Pot, Catalytic, Asymmetric Synthesis of Polypropionates,” Org.Lett. 2001, 3, 1499-1501.
Education
B.S. 1988 University of Vermont
Ph.D.1993 Harvard University