n e w s of t h e w e e k back-to-back moves, Kurt M. Landgraf resigned as chairman and CEO of DuPont Pharmaceuticals and the company announced that it had ended negotiations with Aventis over a possible drug research and marketing alliance in Europe. Soon after, Richard U. De Schutter, formerly chairman and CEO of G. D. Searle, joined DuPont in July to evaluate strategic alternatives for the drug business. The result: the decision to get out. Patricia Short and Karen Watkins
Evaluating Chemical Risks Facing Children
Several phthalate esters, suspected by some researchers of disrupting the human hormone system, were considered for the first round of testing but were not included. EPA says it is waiting for assessments of phthalates being conducted by the National Toxicology Program, the Consumer Product Safety Commission, and the Food & Drug Administration before deciding whether to seek tests on these chemicals. Those assessments are expected to be finished in the next six to nine months, EPA says. The agency also deferred a decision on whether to include styrene in the children's chemical testing program, in part because manufacturers and users of the chemical are already sponsoring toxicological research on the substance. In its second announcement, EPA laid out details of its High Production Volume (HPV) Challenge Program. This initiative, in the works for more than two years, involves determining basic health and environmental effects of some 2,800 chemicals produced or imported in the U.S. in quantities of at least 1 million lb per year. EPA says 469 companies, either individually or as part of consortia, have thus far volunteered to make this data available for 2,155 chemicals. Finally, invoking its authority under the Toxic Substances Control Act, the agency proposed regulations that would force manufacturers and importers of 37 HPV chemicals not covered by voluntary agreements to test their products. If no company volunteers to test the remaining HPV chemicals, EPA will require the studies. Cheryl Hogue
The Environmental Protection Agency is asking chemical manufacturers to voluntarily test 23 widely used substances that children are exposed to in everyday life. This is one of three actions the agency took last week that involve chemical testing. EPA will use data generated in the first round of its Voluntary Children's Chemical Evaluation Program to examine the risk to youngsters from chemicals found in the human body, in food or water that children ingest, or in air. The agency will ask for more tests on these substances if it finds it needs additional information for risk assessment. The agency plans to evaluate and revise the program after the testing of the first 23 compounds and then expand it to include more chemicals. Sandra Tirey, assistant vice president of the American Chemistry Council, says chemical manufacturers are hopeful that the program "can provide the kind of scientific information necessary to further ensure the health and safety of children. Better information From Pacifichem 2000 leads to better decisions—by government, industry, and individuals." The compounds initially covered in the children's chemical testing program are acetone, benzene, chlorobenzene, decabromodiphenyl ether, decane, mdichlorobenzene, />-dichlorobenzene, ndodecane, ^-dioxane, ethylbenzene, eth- Most people would be satisfied with a ylene dibromide, ethylene dichloride, catalyst for asymmetric synthesis that methyl ethyl ketone, octabromodiphe- rapidly gives good yields of chiral prodnyl ether, pentabromodiphenyl ether, ucts in 80% enantiomeric excess (ee) oc-pinene, tetrachloroethylene, toluene, and turns over millions of times before trichloroethylene, undecane, vinylidene giving out. But not the researchers in chloride, m-xylene, and 0-xylene. EPA chemistry professor Ryoji Noyori's labosays companies testing the two listed ratory at Nagoya University in Japan. xylene isomers might want to consider Improving upon earlier successes, studies on p-xy\ene and mixed xylenes they've now devised a robust catalytic system for asymmetric hydrogénation as well.
Catalyst Enhances Asymmetric Ketone Synthesis Yields
8
JANUARY 1, 2001 C&EN
that yields optically active secondary alcohols with close to 100% ee from a wide variety of ketones. Nagoya University associate professor Takeshi Ohkuma reported the group's findings last month in Honolulu at a Pacifichem symposium on discovery and development of asymmetric synthesis and chiral technology. As Ohkuma pointed out, chiral secondary alcohols are ubiquitous features of many biologically active molecules and often serve as key building blocks in syntheses. One way to make such alcohols is to hydrogenate the corresponding ketone. Using a chiral BINAP [2,2'-bis(diphenylphosphino)-l,r-binaphthyl] derivative as a ligand, the Noyori group developed a ruthenium catalyst for asym-
OCHo
Ar 2 CI
H2
χ Ar 2 CI
OChl· H2
|
Ar = 3,5-(CH3)2C6H3 XylBINAP
metric hydrogénation with a turnover number of 2,400,000 and a turnover frequency as high as 228,000 per hour. Hydrogénation of acetophenone, for example, gave 1-phenylethanol in 80% ee. But the researchers hoped to achieve better enantioselectivity. To do so, they replaced the phenyl groups bonded to the phosphorus in BINAP with w-xylenes, figuring the increased bulk would result in higher selectivity. Their reasoning was correct: Using "XylBINAP" as a chiral phosphine increases the ee in the acetophenone hydrogénation to 99%. The reaction proceeds equally well with a wide variety of substrates, Ohkuma said, including heteroaromatic ketones. With α,β-unsaturated ketones, only the carbonyl group is reduced, giv ing an allyl alcohol as the product. The Noyori group has already applied the new asymmetric hydrogénation catalyst to the synthesis of several chiral drugs, including (R)-fluoxetine hydrochloride (Prozac). They've showed, Ohkuma said, that the catalyst can succeed in preparatory-scale reactions. Pamela Zurer
