16 and submit medical documentation by Oct. 17 could begin receiving compensation by next year. About 90,000 women have registered with the court for the settlement, but the actual number of claims will depend on the documentary evidence the court will have to examine. Payments are based on a schedule of benefits contained in the settlement, but depending on the circumstances, an individual payment could be as high as $1.4 million. Most payments will be considerably less. Women are eligible to receive compensation for diseases associated with implants, as well as for evaluation and diagnosis of complications, for removal of ruptured implants, and other medical costs. The judge did, however, make two important changes in the settlement as a result of fairness hearings he held in mid-August. First, women from Australia and the Canadian provinces of Ontario and Quebec have now been excluded from the settlement because of class action court cases now pending in those places. Second, he specifically has set aside $81 million to compensate women suffering implant-related diseases who are not U.S. citizens and are living outside the U.S. The funds are to be paid over the 30-year settlement period. Breast implant manufacturers are up-
beat about the judge's decision. A spokeswoman for Dow Corning, which will provide $2 billion to the settlement, says the company is "pleased" with the decision. A Bristol-Myers Squibb spokeswoman says the judge's decision "marks a great milestone." Bristol-Myers Squibb will make the second largest contribution to the settlement, $1.2 billion. Other major participants in the settlement are Baxter Health Care ($556 million), 3M Co. ($325 million), and Union Carbide ($138 million). However, spokeswomen for Dow Corning and Bristol-Myers Squibb pointed out the complexity of the settlement and said that their companies had the option of dropping out of the settlement until Sept. 9 (after C&EN went to press). Dow Corning is concerned about the 14,000 women who have told the court they will pursue separate court actions against the implant manufacturers. Trying these women's claims on a case-by-case basis could be an expensive proposition. In addition, implant manufacturers could face multi-million-dollar judgments. For example, 3M and McGhan Medical already have seen a $30 million judgment awarded to three women in March by a Texas court (C&EN, March 14, page 8). Marc Reisch
Scientists expect ozone loss to peak about 1998 Stratospheric ozone depletion caused by chlorofluorocarbons (CFCs) and other synthetic halogen-containing chemicals will get worse for the next few years before it gets better, and recovery will only begin then if the world continues to comply with the international treaty banning ozone-depleting compounds. This is the conclusion of an international panel of atmospheric scientists, who predict the ozone layer will begin a slow recovery around 1998. The scientists link the record ozone depletion observed worldwide over the past two years to the 1991 eruption of Mount Pinatubo in the Philippines. The volcano increased the amount of sulfate aerosols in the stratosphere, which exacerbated the ozone-depleting effect of chlorine and bromine from CFCs and halons. However, the panel reports that the buildup of CFCs and halons in the at-
mosphere has slowed recently as a direct result of restrictions dictated by the Montreal Protocol on Substances That Deplete the Ozone Layer. Yet the long lifetimes of the chemicals ensure it will take decades for the ozone layer to recover, the scientists report. "We must not relax," says Robert T. Watson, associate director for environment at the White House Office of Science & Technology Policy. "The Montreal protocol is starting to have an effect," but "we are very susceptible to severe ozone depletion while chlorine and bromine concentrations remain high, especially if we get a long cold winter in the Arctic or another major volcanic eruption." Watson was one of three cochairmen of the 1994 report, "Scientific Assessment of Ozone Depletion," prepared by 226 scientists from 29 countries under the auspices of the United Nations Environment Program. The report points out
Watson: ban is starting to work there is little more the world can do to affect the magnitude or timing of the peak ozone loss. However, implementation of some policies, such as tighter controls on hydrochlorofluorocarbons and methyl bromide, could speed recovery of the ozone layer. The report, along with forthcoming environmental and technology assessments, will be considered by the parties to the Montreal protocol when they convene in 1995. Earlier assessments helped catalyze the movement to strengthen the Montreal protocol in 1990 and again in 1992. The current terms of the treaty ban production of CFCs, carbon tetrachloride, and methyl chloroform as of Jan. 1, 1996. A ban on halon production took effect last Jan. 1. Pamela Zurer
Process for degrading PCBs receives patent A patent was issued last week for a new process, invented by two Princeton University chemists, that destroys polychlorinated biphenyls (PCBs)— industrial oils that have become one of the most recalcitrant environmental pollutants. Chemistry professor Jeffrey Schwartz and postdoctoral research associate Yumin Liu have developed a titanium compound to carry out the reduction of chlorine to chloride in heavily chlorinated PCBs, producing compounds that are easily degraded by ordinary soil microorganisms. SEPTEMBER 12,1994 C&EN
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NEWS OF THE WEEK Noting that lightly chlorinated compounds are labile under aerobic conditions, Schwartz explains their strategy was to find a reagent that would convert heavily chlorinated PCBs into less-chlorinated compounds so that natural degradation processes could take place. Soils contaminated with PCBs often are treated by stripping the contaminated soil and shipping it to a landfill or to an incinerator—treatments that are expensive and sometimes ineffective. High-temperature incineration is very costly and may not be effective for very heavily chlorinated compounds, which don't burn easily. And incineration may leave toxic residues in the remaining soil or send toxic by-products into the atmosphere. Drawing on their experience in organometallic catalysis, Schwartz and Liu developed a titanium(III) compound that is oxidized to titanium(IV) during the reduction of PCBs and recycled by means of reaction with sodium borohydride. Eventual by-products are in-
nocuous titanium dioxide and sodium borate. The process "targets the heavily chlorinated actors with a reduction reaction," Schwartz says. "It uses a cheap catalyst, and it's simple. The method has a good chance of succeeding in practice." Princeton University, which holds the patent, has granted a worldwide license to Xetex Corp., a New York-based startup company. Tests of the technology are scheduled to be conducted in a field trial on a contaminated site in Pennsylvania this fall. After those field tests are completed, an application to the Environmental Protection Agency will be made for approval and certification of the method as an acceptable PCB cleanup procedure. The Princeton research was sponsored by Texas Eastern Transmission Corp., a Houston-based natural gas pipeline company, which is responsible for cleaning up dozens of sites in 14 states under the terms of a court settlement with EPA. Deborah lllman
kinase C enzymes are a subclass of protein kinases that play an important role in cellular growth control, regulation, and differentiation. Activation of protein kinase C enzymes promotes cellular proliferation and gene expression, and has been implicated in a number of diseases, including cancer, cardiovascular disorders, asthma, diabetes, central nervous system dysfunction, and AIDS. And some compounds that activate protein kinase C enzymes, such as phorbol esters, are known tumor promoters. Thus, several biotechnology and pharmaceutical companies are earnestly seeking protein kinase C inhibitors as potential therapeutic drugs. "There's been a lot of activity around compounds of the staurosporine class," says Hughes, "but these are not generally selective." That is, they do not inhibit specific protein kinase C enzymes to the exclusion of other protein kinases needed for normal body functioning. Staurosporine is a microbial product that exerts its effects, in part, by competing with ATP. Hughes points out that balanol is one of the most potent protein kinase C inhibitors yet found. "It's not a whole lot Two groups of researchers have inde- eases associated with protein kinase C more potent than compounds of the staurosporine class," he says, "but it difpendently synthesized balanol, a natu- activation. ral product from fungi that has been One of the total syntheses of balanol fers rather dramatically in structure from shown to be a potent inhibitor of pro- has been achieved by John W. Lampe, compounds of that class. So it's a new tein kinase C enzymes. The work could Philip F. Hughes, Christopher K. Big- lead into protein kinase C inhibitors." lead to the development of balanol an- gers, Shelley H. Smith, and Hong Hu of In the two total syntheses of balanol, alogs as potential new drugs against the department of chemical research at similar synthetic techniques are used to cancer and a wide range of other dis- Sphinx Pharmaceuticals Corp., Durham, assemble the top part of the molecule, N.C. [/. Org. Chem., 59, containing the benzophenone system. 5147 (1994)]. The other "It's surprising that two groups that synthesis was carried had not been conversing at all would out by K. C. Nicolaou, come up with strategies that look so Mark E. Bunnage, and similar," says Hughes. Kazunori Koide of the However, the teams' approaches to departments of chemis- the seven-membered nitrogen heterotry at Scripps Research cyclic ring are fundamentally different. Institute, La Jolla, Calif., The two groups "started with different and the University of precursors," says Nicolaou, "and used California, San Diego different techniques to cyclize the [/. Am. Chem. Soc, 116, ring." 8402 (1994)]. Both paHughes says the practical rationale for pers were published the work was to facilitate the synthesis last week. of balanol analogs, over 400 of which In molecular model of The protein kinases have now been made at Sphinx. In addibalanol, carbon is are a large family of tion, he says, "We wanted to make both black, hydrogen is enzymes that transfer enantiomers to make sure the activity rewhite, oxygen is red, and nitrogen is purple. phosphate from aden- sided in only one." The enantiomer reposine triphosphate resenting the natural product turned out Image courtesy of K. C. (ATP) to proteins as a to be the active one. Nicolaou and Luigi means of regulating Balanol was also originally isolated Gomez-Paloma, Scripps protein activity. Protein independently by two groups. The Research Institute
Balanol total synthesis achieved by two groups
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SEPTEMBER 12, 1994 C&EN
