Organic chemistry: Just add water
Published online 28 April 2010
Partially hydrolyzed titanium catalysts boost the efficiency of amino acid synthetic pathways to levels suitable for industrial applications
Fig. 1: A new, partially hydrolyzed titanium catalyst allows selective synthesis of amino acid precursors at room temperature.
© 2010 C. Chai and A.M. Seayad
Amino acids are often called the building blocks of life because, from a small range of 20 molecules, cells can assemble large numbers of diverse and complex protein structures. Chemists are constantly searching for new ways to synthesize amino acids in order to mimic, characterize and influence the function of biomolecules. They are also sought as intermediates for the production of pharmaceuticals.
Now, in a collaborative project with Mitsui Chemicals Asia Pacific, researchers led by Christina Chai and A.M. Seayad from the A*STAR Institute of Chemical and Engineering Sciences in Singapore1 have developed a highly selective catalyst system that can perform a key step of the amino acid synthesis at room temperature—an important increase in efficiency that will garner attention from industry.
Controlling the spatial orientation of molecular units within an amino acid is a challenging task. When the amino acid contains an asymmetric bonding site, two chiral enantiomers—isomers that are mirror images of each other—can be formed during an amino acid synthesis. While chemists have designed several methods to form pure enantiomers of amino acids, these routes often require expensive catalysts and low temperatures, from –75 to –40 °C, to work.
Chai, Seayad and their co-workers used an inexpensive titanium-based catalyst (Fig. 1), in combination with a chiral ligand called salicyl-β-aminoalcohol, to improve the chemical reaction between cyanide and a molecule containing a carbon–nitrogen double bond. According to Chai, the chiral ligand coordinates with the titanium catalyst to form a three-dimensional environment that directs addition of the cyanide to only one side of the carbon–nitrogen double bond, leading to a high yield of single enantiomers that can be easily converted to amino acids.
This catalytic reaction, however, is extremely slow, requiring almost a full day for completion. But, when the researchers added a small amount of water to the mixture, they observed a dramatic improvement in both the reaction speed and the yield of pure enantiomers. By pre-treating the titanium catalyst with water, the reaction could be completed in 15 minutes at room temperature, with over 98% enantiomeric purity. The researchers postulate that water modifies the structure of the titanium catalyst and provides hydrogen ions to initiate the chemical transformation, resulting in higher reaction efficiencies.
Because this technique works with a variety of molecular substrates at ambient temperatures, and uses an inexpensive metal material, it promises to provide significant savings in the production of chiral amino acid intermediates due to lower production costs, says Chai.
The A*STAR affiliated authors in this highlight are from the Institute of Chemical and Engineering Sciences
- Seayad, A.M., Ramalingam, B., Yoshinaga, K., Nagata, T. & Chai, C.L.L. Highly enantioselective titanium-catalyzed cyanation of imines at room temperature. Organic Letters 12, 264–267 (2010). | article