Thursday
August 27, 2009 |
 |
Professor Katsunori Tanaka
Dept. of Chemistry, Osaka University |
A New Strategy in Synthetic Biology: From Enzyme Inhibition, Natural Products Synthesis to PET Imaging by 6pi-Azaelectrocyclizations |
1:30 p.m.
331 Smith Hall |
Chris Douglas |
Abstract: During inhibitory studies of the hydrolytic enzyme by aldehyde-containing natural products, a reaction involving 6p-azaelectrocyclization with lysines was discovered. Substituent effects within the 1-azatriene systems, the precursor of cyclization, accelerated the reaction. Structure-reactivity studies showed that the azaelectrocyclization, which usually proceeds in low yield at high temperatures, could be performed quantitatively in less than 5 min at rt. The asymmetric chiral piperidine synthesis and the one-pot library synthesis of pyridines on solid-supports were applied to the synthesis of pyridine / indole alkaloid-type natural products.
A lysine-based labeling of biomolecules based on rapid 6p-azaelectrocyclization has also been developed. Both DOTA as a metal chelating agent (either for MRI, PET, or other radiopharmaceutical purposes, e.g., SPECT with gamma emitters) as well as fluorescent groups were introduced efficiently and selectively into lysine residues within 10 min at concentrations even at 10-8M. The DOTA-labeled somatostatin, glycoproteins, and glycoclusters were then radiometallated with 68Ga and the receptor-mediated accumulation of somatostatin in pancreas was observed. Further, oligosaccharide dependent circulatory residence of glycoproteins, and the specific accumulation of the N-glycan-clusters could be visualized for the first time by microPET.
"A whole cell-based in vivo imaging" via direct chemical labeling of living cells, the chemical engineering of antibodies and/or cell surfaces by natural N-glycans based on azaelectrocyclizations, and the combined solid-supported/microfluidic technologies toward oligosaccharides synthesis, will also be presented. |
Tuesday
November 17, 2009 |
|
Professor Matthias Brewer
Dept. of Chemistry, University of Vermont
website |
Ring Fragmentations and Intramolecular Cycloadditions: Efficient Approaches to Nitrogen Heterocycles |
9:45 a.m.
331 Smith Hall |
Chris Douglas |
| Abstract:
Our work has recently focused on developing new synthetic organic methods for the preparation of nitrogen-containing heterocycles. In this presentation I will discuss two methods we are developing that provide bi- or tricyclic heterocycles from simple linear precursors. The first approach stems from our work on the reaction of hydrazones with sulfonium salts, which provide a variety of products including diazo compounds. We have also observed that aryl substituted hydrazones containing a pendent alkene react with sulfonium salts to provide bicyclic diazenium salt heterocycles. The second approach is based on our discovery of a Lewis acid mediated ring fragmentation of certain α-diazo carbonyl compounds, which provides tethered aldehyde ynoates in high yield. Our efforts to incorporate this ring fragmentation into an efficient three-step route from α-silyloxy ketones to polycyclic 2,5-dihydropyrroles, a structural framework in many alkaloid natural products, will be discussed. |
