Research Interests
My main research interests are in developing new reactions
of organic (carbon-based) molecules with the eventual aim
of applying these new synthetic methods to the preparation
of drugs.
As in the movie "Medicine Man", in which Sean Connery
finds a powerful new drug in the Amazon jungle, biologists
are constantly screening plants, trees, and even sponges from
the ocean to see if they produce any compounds which might
have some medicinal use. If we imagine the hypothetical situation
in which these biologists have discovered the perfect drug
that will cure cancer, the so-called magic bullet, what do
we do next? It is likely that the plant or animal which produces
this compound only produces a very small amount of it. How
do we produce enough to treat everyone who needs it?
In the case of taxol (shown below), a chemotheraputic agent
now widely used in the treatment of cancer, harvesting enough
bark from the Pacific Yew tree which produces it to supply
as much of the drug as needed would have quickly killed all
of the trees in existence. Through chemical synthesis, a compound
which is found in the Yew leaves can be converted into taxol
which can then be used to treat cancer patients without harming
the trees.
Since we don’t know what the next miracle
drug may look like, we prepare for this kind of situation
by figuring out good ways to make every possible kind of molecule.
Asymmetic synthesis
One important challenge in the chemical synthesis of drugs
is stereocontrol. Just as our two hands are non-superimposable
mirror images of each other, each chemical compound used as
a drug also has a mirror image. Our bodies interact with these
two mirror images in different ways so that two compounds
which differ in only their handedness can have completely
different scents; one smells like spearmint and the other
licorice in the case of carvone.
It is important that the drugs we use have only
the hand of the compound which is actually interacting with
your body to cause the intended effect. In some cases the
other hand can cause serious side effects. The anti-nausea
drug thalidomide is an example of this. One hand of thalidomide
worked to suppress the symptoms of morning sickness in expectant
mothers. The other hand, unfortunately, resulted in serious
birth defects in children born to the women who had taken
thalidomide. This is why it is important that we develop ways
to make only one hand of a drug at a time.
One way of controlling which hand of a product
is formed is to use a chiral auxillary, a temporary group
added to a molecule which has it’s own handedness. Part
of my research involves using chiral auxillaries in reactions
to control the stereochemistry (handedness) of the reaction.
Tandem Cyclizations
Another research interest is focused on tandem cyclications
between unsaturated aldehydes (those with double bonds) like
2 and Meldrum’s acid (compound 1).
Tandem means two processes happening in a row
and in this reaction, there are actually two different reactions
taking place consecutively. In the example shown, you can
see that in the first reaction, a Knoevenagel condensation,
a molecules of water is lost. This gives us the structure
shown in the middle which will automatically undergo a reaction
called a Diels-Alder reaction generating two new rings. This
whole process happens in a few minutes and in good yield (Tietze,
et. al. Org. Syn.1990, 61, 31-39). We have
been working to determine what other kinds of aldehydes can
be used in this process.
Recent Publications
Barry B. Snider, Rachel B. Smith. "Total
Synthesis of (+)-Fusaricide", Synth. Comm.,2001,
31, 2667-2679.
Barry B. Snider, Rachel B. Smith, "Mn
(III)-Based Oxidative Free-Radical Cyclizations of Alkenyl
Meldrum's Acids", Tetrahedron, 2001,
57, 9846-56.