which are more linear than spherical— predominate when zeolites have tubular cavities, like pentasils ZSM-5 and ZSM-11. Commenting on the research, chemistry professor Galen D. Stucky of the University of California, Santa Barbara, By confining reactants to a particularly points out that although the reactions shaped space, zeolites can direct photo- were carried out to only about 30% conchemical reactions to specific products, version, "in some cases, the selectivity is according to work by chemists at Tulane excellent, and the work represents a sigUniversity, New Orleans. Their findings nificant achievement." may be useful for fine chemical syntheThe Tulane work is an excellent exses and could lead to a new approach to ample of how noncovalent interactions "clean" chemistry. can be used to direct nonselective reacChemistry professor Vaidhyanathan tions to specific products, adds Columbia Ramamurthy, postdoctoral fellow Kasi University chemistry professor Nicholas Pitchumani, and graduate student Manoj J. Turro, who pioneered the concept of shape selectivity for controlling photochemical reactions. "It provides insight to the mechanism of size and shape selectivity of porous solid catalysts under mild conditions," he says. In these reactions, the zeolite is merely a medium, not a catalyst, Ramamurthy stresses. Its shape and the cations within the cavity constrain the transition state, forcing the reaction to form the product Ramamurthy: create chiral space In zeolite with a shape similar to that of the cavity. He hopes the work will spur interest V. Warrier have shown that the interior of a zeolite can control selectivity in the in photochemical reactions for industrial photochemical rearrangements of aryl es- processes, very few of which are used at ters \J. Am. Chem. Soc, 118, 9428 present. Earlier, his group and a team led (1996)]. Some products of such rear- by chemistry professor John R. Scheffer rangements are important precursors of at the University of British Columbia, pharmaceutical compounds. For exam- Vancouver, used zeolites as a medium for ple, conversion of phenyl acetate top-hy- photochemical asymmetric synthesis \J. droxyacetophenone is a key step in pre- Am. Chem. Soc, 118, 1219 (1996)]. paring the analgesic acetaminophen. "The ideal would have been to use Aryl ester rearrangements usually are chiral zeolites. But those are not availdone in solution, using catalysts like alu- able," Ramamurthy notes. So the reminum trichloride and mineral acids searchers inserted optically active comsuch as hydrofluoric or sulfuric acid. This pounds to create the chiral space in the generates large amounts of toxic wastes, zeolite. For photochemical conversion of Ramamurthy notes. The reactions form c/s-4-ter£-butylcyclohexyl ketones to cyphenol and both ortho and para isomers clobutanols, ephedrine was the best of a second product. Because of the poor chiral inductor, yielding 25 to 30% enanselectivity, controlling product distribu- tiomeric excesses. These yields are poor, he says, but they suggest an important tions is difficult. The Tulane study shows there is more role for zeolites in photochemical asymselectivity when the rearrangements oc- metric synthesis. cur photochemically in zeolites. Ortho "There is a perception that photoisomers, which have a more rounded chemical reactions are messy and diffishape, are formed in great excess within cult to control," he says. "Our work is zeolites with spherical cavities, such as showing that the scene is changing." faujasites X and Y. But para isomers— Maureen Rouhi
Zeolites steer photoreactions to precise products
Genomics-based drug discovery venture Genetics Institute has launched a genebased protein drug discovery platform and signed on two major biopharmaceutical firms as its first licensees. The Cambridge, Mass.-based company calls its DiscoverEase program "functional genomics"—designed to isolate and rapidly determine not only genes but also the related functions of critical proteins. Other genomics programs sequence vast amounts of human genetic information. But Genetics Institute suggests the race is not to uncover the most genes, but rather the most valuable ones to speed up gene-based drug discovery. Chiron, of Emeryville, Calif., and Genentech, of South San Francisco, have joined the program to increase their sources for drug leads. Genetics Institute is offering broad access by multiple partners for what it calls "low up-front fees." It retains an option to codevelop and cocommercialize any resulting products based on individual proteins selected by partners for exclusive licensing. It is not surprising that the first licensees are biopharmaceutical companies that have successfully developed and marketed several recombinant proteinbased drugs. Genetics Institute's technology targets similar "secreted proteins" produced by cells to mediate biological functions and interactions. The company says it has used its "signal sequence trap" technology, which identifies and isolates fragments of genes encoding for secreted proteins, to identify 5,000 secreted gene fragments. To date, it has identified 250 of the associated proteins. Genetics Institute—in which American Home Products holds a majority share—is entering the competitive and lucrative field of genomics research. Large pharmaceutical firms have eagerly promised significant sums to access gene sequence libraries to find potential drug targets. More than 15 major drug firms already have licensing deals with three leading genomics firms: Human Genome Sciences, Rockville, Md.; Millennium Pharmaceuticals, Cambridge, Mass.; and Incyte Pharmaceuticals, Palo Alto, Calif. Not including all possible R&D milestone and royalty payments, these deals are valued at more than $600 million combined. Genetics Institute anticipates signing additional partners in the U.S., Europe, and Japan by the end of the year. Ann Thayer OCTOBER 7, 1996 C&EN 7
