Thomas A. Spencer
New Hampshire Professor of Chemistry Emeritus
Professor Spencer has research interests in several areas of organic and bioorganic chemistry. All of these projects have involved organic synthesis; some have also involved various biochemical experiments, often in collaboration with other laboratories, with an emphasis on several aspects of steroid chemistry and biochemistry. For example, the discovery in our laboratory that normal cholesterol biosynthesis produces also a small amount of 24(S),25-epoxycholesterol led to investigations of the roles of this and other oxysterols in the regulation of cholesterol metabolism. Another project in this area has been the design and synthesis of photoactivatable analogs of cholesterol and phospholipids for use in covalent labeling of proteins involved in HDL formation and reverse cholesterol transport. An ongoing interest in the mechanisms of enzymes involved in cholesterol biosynthesis has led to a current focus on investigating how biochemical carbocation intermediates can be stabilized by π complexation with the side chains of aromatic amino acids. This project, currently being pursued computationally in collaboration with Professor Robert Ditchfield, has recently provided the first quantitative evaluation of the stabilization afforded by such a π complex, that of a phenylalanine residue with a tertiary carbocation produced in the reaction catalyzed by geranyl diphosphate C-methyl transferase.
“Carbocation-π Interaction: Evaluation of the Stabilization by Phenylalanine of a Biochemical Carbocation Intermediate", Ditchfield, R.; Spencer, T.A. Org. Biomol. Chem. 2016, 14, 9543-9548
"Carbocation-π Interaction: The 1,1 - Dimethylallyl Cation and Benzene", Ditchfield, R.; Spencer, T.A. Tetrahedron Lett., 2011, 52, 3674-3677
"Bridged Aromatic Alkenes for the Study of Carbocation-π Interaction", Spencer, T.A.; Popovici-Müller, J,; van Beusichem, B; Viscardi MacMillan, C.; Lavey, C.F.; Sin, J.M.; Ditchfield, R. Tetrahedron, 2010, 66, 4441-4451.
"Synthesis of Benzophenone-Containing Fatty Acids", Gan, Y.; Wang, P.; Spencer, T.A. J.Org. Chem., 2006, 71, 9487-9490.
"Cholesterol Surrogates Incorporating a Benzophene as Part of the Sterol Tetracycle", Gan, Y.; Spencer, T.A. J.Org. Chem., 2006, 71, 5870-5875.
"Neonsteroidal Benzophenone-Containing Analogs of Cholesterol", Gan, Y.; Blank, D.H.; Ney, J.E.; Spencer, T.A. J.Org. Chem., 2006, 71, 5864-5669.
"Preparation and Biochemical Evaluation of Fluorenone-Containing Lipid Analogs", Spencer, T.A.; Wang, P.; Popovici-Mueller, J.V.; Pelltan, ID.; Fielding, P.E.; Fielding, C.J. Bioorg. Med. Chem. Lett., 2006, 16, 3000-3004.
"Molecular Mechanism of Reverse Cholesterol Transport: Reaction of Pre-B- Migrating High-Density Lipoprotein with Plasma Lecithin/Cholesterol Acyltransferase", Nakamura, Y.; Kotite, L.; Gan, Y.; Spencer, T.A.; Fielding, C.J.; Fielding, P.E. Biochemistry, 2004, 43, 14811-14820.
"Benzophenone-Containing Cholesterol Surrogates: Synthesis and Biological Evaluation", Spencer, T.A.; Wang, P.; Li, D.; Russel, J.S.; Blank, D.H.; Fielding, P.E.; Fielding, C.J. Lipid Res., 2004, 45, 1510-1518.
"Synthesis of Benzophenone-Containing Analogues of Phosphatidylcholine:, Wang, P.;Blank, D.H.; Spencer, T.A. J.Org. Chem., 2004, 69, 2693-2702.