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
compound was discovered in a fungus that grows on pine needles by Palaniappan Kulanthaivel and coworkers at Sphinx [/. Am. Chem. Soc, 115, 6452 (1993)]. It was also isolated from a different genus of fungi by Shoichi Ohshima and coworkers at Nippon Roche Research Center, Kanagawa, Japan [/. Antibiot., 47, 639 (1994)]—who call it azepinostatin, instead of balanol. Stu Borman
Rule aims to sharply cut incinerator emissions The Environmental Protection Agency has proposed stricter air pollution standards for municipal waste incinerators that would dramatically reduce emissions of metals, acid rain precursors, and dioxins. This regulation will replace 1991 emissions standards, require improved pollution control equipment, and cover more pollutants. The proposed regulation, says EPA Administrator Carol M. Browner, "represents the strongest action ever taken to control emissions from municipal incinerators. This proposal will result in major reductions in dioxin emissions and other air pollutants." After a comment and review period, the regulation is expected to become effective in September 1995. The regulation will require existing municipal incinerators to install highefficiency scrubbers, or their equivalents, to reduce air emissions. Currently, these incinerators can use spray driers and electrostatic precipitators for pollution control. EPA says the new restrictions will apply to incinerators burning as little as 40 tons per day of trash. The current compliance threshold is 250 tons per day. This lower threshold will lead to regulation of an additional 180 existing incinerators and all new facilities, according to EPA. The proposed standards are designed to reduce emissions of a number of compounds from incinerators. According to EPA calculations, scrubbers should be more than 99% efficient in the reduction of metals such as lead, cadmium, arsenic, and chromium from incinerator stack emissions. These metals were not specifically controlled in the 1991 regulation. Acid gas emissions, including sulfur dioxide and hydrogen chloride, should
be reduced by more than 90% and 97%, respectively. The old standards only required 70% reduction in sulfur dioxide and 90% reduction in hydrogen chloride. All new municipal incinerators will have to meet the emissions standards. But before such a facility can be built, a number of requirements set forth in the proposed regulation will have to be met. These requirements include public involvement early in the incinerator planning stage, preparation of an incinerator plant siting analysis, and development of a materials separation and recycling plan.
The incinerator industry has been working closely with EPA in anticipation of this regulation, according to Kevin Stickney, vice president for public affairs at Wheelabrator Technologies in Hampton, N.H. "Overall, the regulation will have little impact on our operations. Most of our facilities have already been retrofitted to meet the new standards," Stickney says. Wheelabrator Technologies is one of the largest operators of municipal trash-to-energy incinerator companies, running 16 facilities in the U.S. that burn 22,000 tons per day of trash. David Hanson
Johnson & Johnson to buy Kodak diagnostics unit Johnson & Johnson and Eastman Kodak reached an agreement last week for J&J to acquire Kodak's clinical diagnostics business for $1.01 billion in cash. The move further diversifies J&J away from prescription pharmaceuticals and solidifies its position as the third largest player in the medical testing industry. U.S.-based Abbott Laboratories and Germany-based Boehringer Mannheim are first and second, respectively, in the clinical diagnostics market. Kodak's clinical diagnostics business includes clinical chemistry and immunodiagnostic analyzers used in hospitals and by doctors, with sales in 1993 of $535 million. If the Kodak acquisition is folded into J&J's Ortho Diagnostic Systems division, the expanded division's total annual sales will exceed $1 billion. "This acquisition fits perfectly our strategy objective of enhancing our business in diagnostic products," says Ralph S. Larsen, J&J's chairman and chief executive officer. Among these are blood virus screening and diagnostic products used in blood donor centers, hospitals, and other laboratories, and home test products for blood glucose monitoring, pregnancy testing, and other applications. Upon regulatory agency approval of the deal, J&J will receive all personnel, patents and technology, production equipment, and products associated with Kodak's clinical diagnostics business. Kodak will continue to provide customer equipment service support to J&J's customers. J&J says it will continue to operate all
four locations of Kodak's clinical diagnostic business, which employs about 2,800 workers worldwide. Those locations include Rochester, N.Y.; Cardiff, Wales; Pollards Wood, England; and, Strasbourg, France. J&J finished 1993 with total sales of $14.1 billion. The company's medical supplies and diagnostics segment contributed $4.82 billion of that, and its prescription pharmaceutical segment contributed $4.49 billion. The remaining $4.82 billion came from J&J's consumer products segment. In 1993, prescription pharmaceuticals accounted for about 55% of J&J's $1.79 billion in earnings. But with the advent of managed health care in the U.S., drug prices likely will continue to drop, leading companies, including J&J, to look for other businesses with higher earnings potential. The latest acquisition comes after New Brunswick, N.J.-based J&J's $924 million bid on Aug. 22 to purchase Los Angeles-based Neutrogena, a maker of soaps, shampoos, and skin creams. Kodak's sale of its clinical diagnostics business nearly completes the company's divestment of noncore assets in its drive to focus on imaging and related businesses. The company recently signed agreements to sell the prescription drug business of Sterling Winthrop to Sanofi for $1.7 billion and the overthe-counter drug business of Sterling to SmithKline Beecham for $2.93 billion (C&EN, Sept. 5, page 4). Still left for Kodak to divest is the L&F consumer products business, which makes Lysol disinfectants, among other products. George Peaff SEPTEMBER 12,1994 C&EN
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