Preparation of a Novel Heterogeneous
Titanocene Catalyst for Chiral Reduction and Asymmetric Polymerization
Johannes G. Khinast
Dept. of Chemical & Biochemical Engineering
Due
to the ongoing biological revolution, new drugs are becoming increasingly
complex, specific and potent. Biological messenger molecules and cell surface
receptors, i.e., the targets that medicinal chemists try to affect, are
asymmetric (chiral). Thus, many drugs are three-dimensional "chiral"
molecules with several stereoisomers possessing significant pharmacodynamic,
pharmacokinetic and/or toxicological differences.
Chirality
refers to the fact that two molecules
may have the same composition, but are mirror images of each other. A typical
example of a chiral system are the right and left hands. Both hands have the
same number and types of fingers (composition), but clearly they are not
identical. Well-known examples of chiral drugs include ibuprofen in which one
isomer is biologically inert and the other is an analgesic. Another example is
the controversial drug Thalidomid®, which contains a racemic mixture
that was given to pregnant women for morning sickness and nausea during the
first and second trimesters. Only too late was it discovered, that the
(R)-enantiomer was tertragenic and blocked the cells of growing limbs in
fetuses, thus causing children to be born with very short arms and legs. For
this and other reasons, an increased effort is being made to administer drugs
in their enantiopure form.
Our
research focuses on the development of chiral catalysts, i.e., catalysts that
selectively produce only the desired stereo-isomer. Most chiral catalysts
developed to date are organometallic soluble (homogenous) complexes which,
unfortunately, cannot be removed from the reaction mixture easily. Thus,
another aim of our work is to immobilize these complexes on solid particles,
which can be removed from the reaction mixture by filtration and can be reused.