by benzene coupling. There are many other examples of novel polymers waiting to be polymerized from available monomers.

Cationic polymerization continues to be an area of increasing research made possible by improved Lewis or Brønsted acid catalysis. Continued improvement is desired to yield higher molecular weights and industrially acceptable process conditions. Extension to other monomers (e.g., vinyl acetate) would be of future interest. Anionic polymerization is of interest primarily for unique block copolymers. Extension to additional monomers and the resultant block structures deserves more attention.


There can be no question that the 1990s will be the "decade of chirality." Many of the opportunities and challenges in this explosively evolving field stem from the pharmaceutical area and the growing recognition that the "wrong" enantiomer of a racemic drug represents a "medical pollutant" whose toxic side effects can far outweigh the therapeutic value of the pharmaceutically active enantiomer. The classic example in this area is that of thalidomide (Figure 2.4). The R-isomer of thalidomide is an effective sedative; tragically, the drug was sold as the racemate, and it was subsequently discovered that the S-isomer is a powerful teratogen. More recently, Eli Lilly was forced to withdraw its Oraflex anti-inflammatory because of liver damage caused by the ''inactive" R-isomer. Although recent regulatory changes by the Food and Drug Administration stopped short of requiring that all drugs be sold as a single enantiomer, there is an obvious trend in this direction by drug companies.

Among the available strategies for the manufacture of optically pure substances, asymmetric catalysis provides powerful and unique advantages. Perhaps the foremost is the "multiplication of chirality"—the stereoselective production of a large quantity of chiral product by using a catalytic amount of a chiral source. Unlike fermentation, asymmetric catalysis is characterized by generality: processes are not limited to "biological"-type substrates, and the R- and S-isomers are made with equal ease. Asymmetric catalysis also circumvents the disposal of large amounts of spent nutrient media that are generated during fermentation. By comparison, optical resolution (i.e., diastereomeric crystallization) is extremely labor-intensive and necessarily produces 50% of the "wrong" isomer, which must be destroyed or racemized in a separate step.

Given the increasing importance of enantioselective synthesis, it is important that the United States place greater emphasis on this area. At present, Japan and the European Community are the leaders in basic research discoveries and applications.

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