People - [ Faculty ]
Over the years, my group has broadly been interested in the synthesis of oxygen heterocycles, and we have developed novel routes to tetrahydrofurans, tetrahydropyrans, and spiroketals which have been documented in the chemical literature. Most recently, we have turned our attention to the synthesis of biologically-active flavonoids and related substances. There is an increasing interest in naturally-occurring polyphenols, largely because of their potential medicinal properties. The green tea extract epigallocatechin-3-gallate, for example, is currently undergoing phase I clinical trials as a potential cancer chemopreventive agent for prostate and breast cancer. Similar compounds have been shown to be inhibitors of HIV 1 replication in vitro, and viral reverse transcription, while a specific trimeric procyanidin in cranberries has been shown to fight urinary infections by preventing E. coli from sticking to the cells that line the urinary tract.
Isolated from the root of Stellera chamaejasme L., a traditional Chinese herb, isochamaejasmine was found to alter several cell-signaling pathways, which could explain its use in the treatment of solid tumors, as well as tuberculosis. It has also been found to be active against several tumor cell lines including human myeloid leukemia cells. Structurally-related analogues of this compound have demonstrated antimalarial activity. A close relative of this compound, chamaejasmine, has been shown to possess both anti-inflammatory activity and aldose reductase inhibiting activity, suggesting that it could be a potential treatment for the complications associated with diabetic neuropathy. Efforts are currently underway in our lab to design synthetic routes to each of these natural products.
“Suzuki coupling reactions of 2,4,6-trialkoxyphenylboronic acids with enol triflates: Asymmetric synthesis of a lactone template for Calyxin assemblage” Sidika Polat Cakir and Keith T. Mead, Tetrahedron Letters 2006, 47, 2451-2454.
“Reactions of N-Acyl Imines with Dihydropyrans” Sidika Polat Cakir and Keith T. Mead, Synthesis 2008, 871.
“Evidence for π Stacking as a Source of Stereocontrol in the Synthesis of the Core Pyranochromene Ring System common to Calyxin I, Calyxin J, and Epicalyxin J” Sidika Polat Cakir, Sean Stokes, Andrzej Sygula, and Keith T. Mead, J. Org. Chem. 2009, 74, 7529-7532.
“γ-Lactonizations of 2H-Chromenes via Cyclopropanation” Sean Stokes, Ben Spears, Cameron Laseter, Bobby Barker and Keith T. Mead, Tetrahedron Lett. 2010, 51, 4003-4006.
“Synthesis of Aryl-Substituted 1,4-Dihydroquinolines by [4 + 2] Cycloaddition of Benzyne and 1-Azadienes” Sean Stokes, Markondaiah Bekkam, Madeline Rupp, and Keith T. Mead, Synlett 2012, 389-392.
“Rhodium-catalyzed cyclopropanations of 2-aryl-2H-chromenes with dialkyl malonate esters. A comparison of a-diazo derivatives and phenyliodonium ylides” Sean Stokes, Rachel Mustain, Lydia Pickle and Keith T. Mead, Tetrahedron Lett. 2012, 53, 3890-3893.