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Erland P. Stevens |
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Research Interests Nitrogen heterocycles Boronic esters of aromatic nitrogen heterocyclesThe Suzuki cross-coupling is a very useful reaction that is normally used to make biaryls (1). The starting reagents for the Suzuki coupling are an aryl halide (2) and an aryl boronic acid (3) or ester (4) (Scheme 1). These two species are coupled in the presence of a palladium catalyst. Unfortunately, certain types of heteroaryl boronic esters cannot be readily synthesized. Examples include 2-pyridyl- (5), 2-oxazoyl- (6), and 5-tetrazoyl- (7) boronic esters and acids. We have been investigating the synthesis and coupling of these and related boronic esters. This work is currently funded by the Petroleum Research Fund and Research Corporation.
The Piloty pyrrole synthesis forms a pyrrole (8) from hydrazine (9) and two aldehydes or ketones (10) with at least one enolizable hydrogen (Scheme 2). The Piloty synthesis dates back to the early 1900's and has received relatively little attention despite the utility of pyrroles. In particular, 1,2,5-unsubstituted pyrroles (11) are useful in the preparation of porphyrins (12). We are examining the scope and potential utility of the Piloty pyrrole synthesis.
An established route to triazoles (13) is the cycloaddition of an alkyne (14) with an azide (15) (Scheme 3). A related method is the cycloaddition of a heteroatom-substituted alkene (16) with an azide followed with the loss of HX. We have recently been using this latter process to prepare triazoles. In collaboration with Dr. Karen Bernd in the biology department at Davidson, we have been screening the products for antibacterial and antifungal activity.
Medicinal chemistry Quantitative structure-activity relationships (QSAR) relate biological acivity to the electronic (σ), lipophilic (π), and steric (Es) properties of a drug (Equation 1). Of the many steric paramters that have been developed, the most widely used is the Taft steric parameter, Es. Unfortunately, the Taft parameter often fails to provide quality QSAR equations even when sterics are known to be a significant factor in the activity of the drug. We have been investigating using steric strain energies, such as A-values (Scheme 4), as a steric parameter in developing QSAR equations.log 1/IC50 = c1σ + c2π + c3Es + c4 (1)
Bioorganic chemistry Enzymes are more and more frequently being used in organic synthesis. We have very recently started to explore using horseradish peroxidase (HRP) to affect synthetic transformations. Known reactions of HRP include alkene epoxidations and heteroatom dealkylations. |
