News of the Week
CENTER LINKS ACADEMIC/INDUSTRY RESEARCH The final contractual i's are being dotted and t's crossed in a program that will establish a Center of University of Massachusetts-Industry Research on Polymers (CUMIRP) at the university's Amherst campus. Involving the university, a group of 13 corporations, and the National Science Foundation, the program is a major thrust in current efforts to forge closer research ties between universities and industry. Seed money for the program is being provided by NSF, which will contribute more than $1 million over the initial five-year period of CUMIRP. The commitment for the first year includes $253,000 from NSF, with decreasing amounts in succeeding years, and $20,000 from each industrial sponsor. The intention is that after five years the center will become self-sufficient, dependent only on annual industrial support of about $600,000 (1980 dollars). The initial industrial sponsors for the new center include Allied Chemical; Alcoa; Arco; Celanese; Dow Chemical; Du Pont; Exxon; General Electric; Kendall Co., a subsidiary of Colgate-Palmolive; Eastman Kodak; Monsanto; Union Carbide; and Westinghouse. CUMIRP will involve primarily the polymer science and engineering department of the university, explains Otto Vogl, a department professor. Vogl is coprincipal investigator for the new center along with Richard S. Stein, director of the university's
Polymer Research Institute, the coordinate polymer funding and communication center of the university. Program manager for the new center is Eugene E. Magat, now a visiting professor at the university. A steering committee advised by a board including representatives of the sponsoring companies will determine specific research projects. Whatever the specific projects, the center's thrust will be toward basic research, Vogl says. Formally, the center's responsibility will be to carry out research on preparation and solid properties of polymers, with initial emphasis on network polymers and extended lifetime of polymers. This, Vogl notes, will involve work on concepts rather than products, and on new instrumentation techniques and new characterization techniques. A number of knotty problems had to be resolved during a year-long feasibility study leading up to the establishment of the center. A primary example is patent policy. Under the agreement, NSF waives patent rights, the university will hold any patents stemming from the center's research, and the industrial sponsors will be given royalty-free licenses. Although NSF has been lenient in granting patent rights to universities, the contract for the new center for the first time specifically spells out that "the National Science Foundation claims no rights to any inventions made during research supported by this award." NSF explains that this
Vogl and Stein: center's thrust will be toward basic research 4
C&EN Oct. 13, 1980
patent clause is an experiment such as it frequently makes with grants to see what effect the approach will have on the successful outcome of a project. In any event, a bill nearing passage by Congress soon may give patent rights to universities for results from any government-supported research. The polymer science and engineering department at the University of Massachusetts is devoted entirely to graduate studies. It has about 125 graduate students and scientists engaged in polymer research, including 45 postdoctoral research associates and visiting scientists active in the department. CUMIRP is one of a number of university/industry centers set up by NSF with grants made under its industrial program. For example, there is a welding center at Ohio State University and a computer-aided design center at Rensselaer Polytechnic Institute. A polymer processing center at Massachusetts Institute of Technology has graduated successfully into self-sufficiency, with NSF now entirely out of the funding picture. D
EPA plans limits on chlorofluorocarbons The Environmental Protection Agency has put producers and users of chlorofluorocarbons on notice that it intends to issue rules limiting production of the compounds to current levels. In an "advanced notice of proposed rule making" published last week in the Federal Register, EPA says that it is considering two major approaches to CFC control. The first would put an indirect ceiling on the compounds' use through mandatory controls or technology-based standards. These could include requiring recovery and recycle of CFC's from flexible urethane and rigid nonurethane foam production, use of the less effective ozone depleter CFC-502 in supermarket refrigeration equipment, an outright ban on certain Î>roducts or uses of CFC's, or estabishing a baseline for each CFC user and requiring anyone wishing to exceed that baseline to get permission from EPA to do so.
maytansine has been reported by a team at Harvard University, Cam bridge, Mass., led by organic chem istry professor Elias J. Corey [J. Am. Chem. Soc, 102,6613 (1980)]. Maytansine is unusual among cancer drugs because its toxic dose is more than 100 times as great as its therapeutic dose. Most cancer drugs are only slightly less toxic to normal cells than to malignant cells. Side ef fects in the central and peripheral nervous and gastrointestinal systems have concerned clinicians, however. Corey's successful synthesis makes large stocks of intermediates available for preparing maytansine analogs that may lack these side effects. The Harvard chemists already have made some analogs that are being tested at the National Cancer Institute. Like a space program, a total syn thesis also results in new methods that chemists now can use on other projects. Among methods Corey de veloped for maytansine are an aldolbased olefin synthesis, an asymmetric condensation for optically active aldols, and a very mild way to remove methoxyethoxymethoxy (MEM) protecting groups from hydroxyl functions. Corey eventually recruited seven postdoctoral students for the main thrust toward maytansine. The effort took five years. "Many graduate stu dents want their own separate projects," Corey explains. "This was a big enough project to need many people." Other members of the winning maytansine team were Mark G. Bock, A. Richard Chamberlin, Hidetsura Cho, David Floyd, Duy H. Hua, A. V. Rama Rao, and Leland O. Weigel. The overall plan of attack was never much of a problem. Corey early settled on the molecular components that had to go together. In a molecule so densely populated with functional groups, however, problems arose continually in finding reactions that would put 35 carbon, 10 oxygen, three nitrogen, and one chlorine atom, to gether with the 46 attendant hydro gen atoms, in the right positions, controlling configurations at each of eight asymmetric centers, under conditions that would push yields Harvard team over 80% and keep the molecule from synthesizes maytansine falling apart. Corey's olefin synthesis, used twice The antileukemic agent maytansine for maytansine, involved condensa has been a target of synthetic organic tion of the anion of an a-trimethylchemists since 1972, when the late S. silyl aldehyde ieri-butylimine with Morris Kupchan, organic chemistry aldehydes. For the asymmetric aldol professor at the University of Vir condensation, he developed phenyl ginia, Charlottesville, isolated it from (R)-(+)-a:-p-toluenesulfinylacetate fruit of the Ethiopian shrub May- as a reagent. He closed the 19-memtenus ouatus. Chemists in at least bered lactam on an Af-methylaniline seven laboratories have worked on the moiety via a mixed carboxyl-meproblem. Now, total synthesis of I sitylenesulfonyl anhydride.
The second approach, which EPA appears to favor, is that of using eco nomic incentives to reduce use. Under this approach EPA would establish a production ceiling for the industry, measured in "permit pounds," which would allow a producer to vary his mix of products among the various CFC's according to the relative de pletion potential of each. These per mits could be allocated directly either to producers or users or they could be auctioned off by EPA to the manu facturer or user willing to pay the highest price. Whatever rules EPA eventually comes up with will cover chemi cals with the general formula CnClxFyH2n+2-x-yX 0, y 0 , and it will take into account the differing ozone depletion potential of the various CFC compounds. EPA admits that unilateral U.S. action to freeze production at, say, 1980 levels would have little impact. It estimates that, even if uncontrolled growth were allowed until 1990 in the domestic CFC industry, the U.S. contribution toward steady-state ozone depletion would be only 7.5% compared to 4.5% with a production freeze. Significant reductions of 70% from 1980 production levels would reduce that contribution to 1.5%. The contribution from the rest of the world in all cases would be 24.5%. But the agency says adoption of a "no-growth" strategy would signal to other CFC producing and using na tions that the U.S. is concerned about the risk entailed in depletion of the ozone layer and that it is willing to take serious action on the basis of present knowledge. EPA believes that the only acceptable long-term strat egy is "substantial emissions reduc tion," but fears that if it implemented this approach immediately it would weaken the U.S. efforts to produce international action of the same magnitude. EPA is allowing three months for comments on the proposals contained in its advanced notice of proposed rule making and expects to propose the rules early next year. D
Maytansine
"We were using up material at a substantial rate just to find proper reaction conditions," Corey says. Toward the end, for example, the Harvard group tried 25 experiments to find the right way to take off the MEM protecting group without ex pelling a nearby methoxy group. The methoxy group was filed to a hair trigger by conjugation with two dou ble bonds and a benzene ring. The conditions hit upon form a lengthy catalog of precise reagents, solvents, temperatures, times, and modes of addition. In fact, the detailed condi tions for almost all reactions in the maytansine synthesis imply a back ground of other conditions that did not work nearly so well. Along with successes there also were frustrations. Corey hoped to form an (S)-alcohol at one position by asymmetric reduction of a ketone. The only result was the discovery of 15 reagents that gave clean reduction to (R)-alcohol. Corey devised the asymmetric aldol condensation to solve the problem. Π
Union Carbide plans silicones plant Construction will begin in 1981 on a $150 million silicones plant by Union Carbide at the firm's South Charles ton, W.Va., site, with completion scheduled for mid-1983. The compa ny has not specified plant capacity, but industry sources suggest that it could be 50 million lb per year. Products will include surfactants for polyurethane formulations, organofunctional silanes for such uses as surface modification of glass fiber and mineral fillers, standard and specialty oils, antifoaming agents, volatile silicone lubricants for cos metic formulations, emulsions, and intermediates for gum and elastomer manufacture. Beginning with silicon metal, the Carbide plant will produce chlorotrimethyl-, dichlorodimethyl-, and methyltrichlorosilanes, which are Oct. 13, 1980C&EN
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