Page 239 - Chiral Separation Techniques

8.7 Summary 217

pursued by allowing a drug co. to develop and produce a single isomer of a racemic
drug which would allow for application for additional patents that might extend the
life of the drug by up to 20 years. The use of racemic switches is being adopted
increasingly by drug firms as a management strategy as a means for innovators to
counter graphic competition, and the combination of this strategy with the use of
MRT adds an additional layer of intellectual property protection.
Amino acid separations represent another specific application of the technology.
Amino acids are important synthesis precursors – in particular for pharmaceuticals –
such as, for example, D-phenylglycine or D-parahydroxyphenylglycine in the prepa-
ration of semisynthetic penicillins. They are also used for other chiral fine chemicals
and for incorporation into modified biologically active peptides. Since the unnatural
amino acids cannot be obtained by fermentation or from natural sources, they must
be prepared by conventional synthesis followed by racemate resolution, by asym-
metric synthesis, or by biotransformation of chiral or prochiral precursors. Thus,
amino acids represent an important class of compounds that can benefit from more
efficient separations technology.
Specialized types of amino acids for synthesis applications represent a growing
field in the biotechnology industry. Applications include peptide hormones and
growth factors, immunological antigens, enzyme substrates, receptors and ligands,
chemical drugs, bioactive peptides for research, combinatorial chemistry, drug dis-
covery, pesticides, and artificial sweeteners. This market area represents a unique,
high-value niche for companies, and the efficient production of speciality amino
acids is a growing need.
Pharmaceuticals and intermediates represent another important class of com-
pounds. General classes of drugs that may well lend themselves to the IBC technol-
ogy include the chiral non-steroidal anti-inflammatory profen drugs, norephedryns,
and intermediates for a number of important drug classes including β-blockers and
racemic switch candidates.

8.7 Summary

Efficient optical purification of the classes of compounds discussed here presents a
pivotal challenge to industry as we enter the 21st century. In order to meet this chal-
lenge, IBC has developed a series of novel complexing agents with high α-values for
purification of enantiomers. These complexing agents are covalently attached to
solid supports and the resultant ChiraLig™ materials used in non-chromatographic
separations systems. We have demonstrated this technology for the separation of
amines and amino acids, and discussed the potential for further open-ended applica-
tion to other chiral entities. The ligands used are based on molecular recognition
design principles, and can be prepared synthetically on an industrial scale. The resul-
tant separations systems exhibit high selectivity factors, low solvent usage, and high
throughput. The experimental results demonstrate the ability of the technology to