Research
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The department of Bio-organic
Chemistry was established only recently; in November 2007. Before
that time the group was embedded in the department of Synthetic
Organic Chemistry.
In the field of asymmetric synthesis and catalysis, within the group of Prof. Feringa and in collaboration with Prof. de Vries (DSM), we have contributed significantly over the last number of years to the development and application of catalytic asymmetric hydrogenation, catalytic asymmetric conjugate addition and catalytic asymmetric allylic substitution reactions. In the area of asymmetric hydrogenation, novel catalysts have been developed and new substrate classes have been introduced that upon hydrogenation afforded useful building blocks in excellent yield and enantioselectivity.
The isomerisation-free reduction of carbon-carbon double
bonds using a Vitamine B2 inspired catalyst (Smit,
Fraaije, and Minnaard,
J. Org. Chem. 2008)
In the field of copper-catalyzed
asymmetric conjugate addition and allylic substitution, considerable
progress including several breakthroughs has been made over the past
years. The asymmetric conjugate addition of dialkylzincs has been,
together with several other groups around the world, brought further
to perfection in terms of yield and enantioselectivity. Also the
substrate scope was considerably expanded, including several
nitrogen containing building blocks that were before only available
via long synthetic routes with chiral auxiliaries. In this period
also the long sought for catalytic asymmetric conjugate addition of
Grignard reagents has been developed. This approach is more
practical, though less functional group tolerant, than the
dialkylzinc addition. The conjugate addition of Grignard reagents
has been applied in both cyclic and linear substrates, expanded to
double unsaturated compounds and for various Michael acceptors. Also
a thorough mechanistic study on the reaction was carried out. In the
closely related, but considerably less developed, catalytic
asymmetric allylic substitution reaction considerable progress has
been obtained as well, making this reaction now suitable for
synthesis.
A recent example from our research
in asymmetric hydrogenation is the synthesis of Fosmidomycin
analogues, which are mimics of 1-deoxy-D-xylulose 5 phosphate. The
latter compound is an intermediate in terpene biosynthesis and the
corresponding enzyme is an important target in anti-malaria
research. The synthesis of enantiopure compounds that are chiral on phosphorus is a challenge already for decades. These compounds are obviously very important as ligands for homogeneous catalysis. Together with collaborators we reported recently on a convenient preparative method for the synthesis of enantiopure t-butylphenylphosphine oxide based on the resolution via diastereomeric complex formation.
On the use of enzymes in organic synthesis we focused successfully on the preparation of enantiopure building blocks.
In our natural product synthesis
work, next to two alkaloids several complex mycobacterial
glycolipids and polyketides have been prepared, all of them for the
first time. This has allowed a collaboration with the group of Prof.
M.B. Moody ( The asymmetric conjugate addition and direct addition of
arylboronic acids and arylsiloxanes has been studied both with
rhodium and palladium catalysts. We were the first to report the
Pd-catalyzed asymmetric conjugate addition of arylboronic acids and
aryl siloxanes. This Web Page Created with PageBreeze Free HTML Editor |
