Below -
having some fun outside of the lab ... :-)
"GROUP
REUNION/SYMPOSIUM" see also a list of Research interests
Our research
focuses upon the development, use, and
understanding of reactions and reactive intermediates – and their
application to the synthesis
of bioactive and other
structurally interesting materials. We emphasize mechanistic aspects of the chemistry
because we believe in the fundamental importance of them in gaining an
understanding of the chemistry and the intermediates we
investigate. Our efforts
allow the exploration of
the chemistry of a variety of interesting and reactive intermediates,
including diradicals - especially those related to trimethylenemethane,
as well as radical anions and radical cations - the latter
being generated using a variety of electrochemical
techniques.
Current target
structures include molecules containing the bicyclo[5.3.0] core (e.g. daucene) -
accessible using electrocatalytic processes involving the intermediacy
of cation radicals, the pseudopterosins
– a class of marine natural products that display significant
anti-inflammatory and wound healing properties, linearly and angularly
fused tricyclipentanoid
skeleta accessed via a combination of carbenoid and trimentylenemethane
diyl chemistry, and diplopyrone
– a substance of importance in the growth and harvesting of cork and
accessible using C-glycoside chemistry developed in the group.
The
pseudopterosin chemistry involves a collaborative
effort with colleagues
in pharmacology at UCSB including Professor R. S. Jacobs, Dr. Claudia
Moya, and Daniel Day. In addition to studying the natural
products themselves, we are actively engaged in efforts to synthesize
and screen structurally simpler analogues in an effort to determine how
these interesting materials work. A major focus at this time is
to examine the redox properties
of these materials.
One major focal point of our research is upon the chemistry and pharmacology of the pseudopterosin class of marine natural products. We are attempting to (1) determine where the pseudopterosins go when they interact with a G-protein coupled receptor, (2) determine what they do when they get there, and (3) synthesize new structures with significantly improved wound healing properties. In the past week (today is 3 October 2008) we have obtained evidence suggesting that a critical step in the activation of the receptor may be an oxidation of the pseudopterosin core. Our efforts to uncover the details of what we believe to be proton-coupled electron transfer events make use of cyclic voltammetry and preparative scale electrochemical and reagent initiated transformations in order to isolate and characterize the product(s). For an example of some of our recent work in this area, see: J. Org. Chem. (Featured article) 2008, 73, 7011-7016. Another topic of considerable interest focuses upon the mediated, electrocatalytic processes, and upon obtaining an understanding of the fundamental nature of the reactive intermediates produced in this manner, as well as their chemical transformations. As a consequence, we are developing chemistry of both cation and anion radicals. Our radical anion chemistry concentrates upon electroreductive cyclizations of the variety we describe in J. Org. Chem. 2005, 70(20), 8017-8026, while the cation radical chemistry highlights the rearrangements of housane-derived cation radicals (see, for example J. Org. Chem. 2007, 72(12), 4351-4357). We are particularly interested in further explorations of remote regiochemical control, and upon applying our knowledge of these factors to the synthesis of natural products. The cation radicals are being generated in three ways, viz., (1) by using triarylamminium antimony salts; (2) through the use of electrochemical mediators, once again used catalytically; and (3) by direct oxidation at the anode. Thus far, the 2nd and 3rd options have proven most effective and have lead to the cleanest and most reproducible results. This chemistry has matured to the point where we have applied it to the total synthesis of natural products possessing the [4.3.0] and [5.3.0] frameworks. For a recent example of our research activities involving cation radicals, see: J. Org. Chem. 2008, 73(17), 6807-6815. Lastly, in an effort to reduce costs and waste, we are following up on some beautiful work that emanated from Steckhan’s labs, calling for the use of recyclable, polymer bound triarylamine redox reagents to affect the oxidative rearrangement chemistry. We make significant use of quantum mechanical calculations in an effort to understand and rationalize the detailed course of the chemistry we study, with an ultimate goal being to predict the course of as yet untried processes. In addition to our steadily growing efforts at UCSB, we have teamed up with Professor Dean Tantillo of UC Davis to carry out calculations at the highest levels of theory. Here, one of our objectives is to provide a ‘complete’ map of the potential energy surfaces for the cation radical rearrangements. Thus far, the transformations have displayed relatively flat surfaces, suggesting that dynamic effects of the nature first promulgated by Carpenter and coworkers may be playing a role. Finally, we continue our longstanding research activities involving diradicals, particularly those related to trimethylenemethane. At the present time, we are perfecting the development of a new, highly concise route to these reactive intermediates and the rich array of chemical transformations they undergo. For a sample of our work in this area see: J. Org. Chem., 2004, 69(25), 8574-8582. |
