News and Events:
Kenneth Turnbull, ph.d. - research
Research efforts in my group are being carried out in several general areas:
1. Anticancer/ Antiviral Compounds
Some C-nucleosides (DNA or RNA precursors), e.g. pyrazofurin, have proven effective in antiviral strategies. However, for the latter, the therapeutic profile is hampered by the severe side effects and, accordingly, we are preparing analogous compounds, via sydnone functionalization and subsequent cycloaddition with substituted alkynes, with a view to improving their efficacy. This synthetic avenue has the advantage that a variety of potentially bioactive compounds can be prepared from one sydnone nucleoside precursor.
2. Sydnone Antihypertensives
Remarkably, the unstable gas, nitric oxide (NO), plays several major roles in the body, key amongst which is vasodilation (i.e. expansion of an artery) with consequent lowering of blood pressure. One effective antihypertensive is Molsidomin (a sydnone analog) that is now known to exert its effect by release of NO due to enzymatic activation. We are preparing Molsidomin relatives using various synthetic approaches, including the sydnone dilithiation protocols first developed in our lab. Further, we had shown several years ago that the fused sydnobenzotriazine 1 cleaved under hydrolytic conditions to yield the benzotriazine carboxylic acid 2. In retrospect, it appears likely that the by-product of this transformation is a congener of nitric oxide and, accordingly, it is of interest to prepare analogous fused-ring sydnones as possible NO prodrugs.
3. Polymer Supported Reagents
The advantages of such species are reduction in odor (of otherwise smelly reactions), facile removal of reaction by-products and ability to recycle the reagent. Various useful reactions (Staudinger, Aza-Wittig, etc.) are being subjected to conditions of polymeric tethering, with interesting results. Extension to combinatorial protocols also is underway.
4. Photochromic Compounds
Photochromism is the reversible process whereby a substance which was colorless becomes colored (often blue) on exposure to light. Removal of the radiation allows color reversal. Applications are multitudinous and include optical memories, radiation densitometers and photochromic eyeglasses. We have been involved in the improved synthesis of modified pyridinyl sydnones, analogs of known photochromes, with a view to rendering them more efficient, since those currently known switch back and forth on the geological time-scale!