NEWS OF THE
WEEK
The trend of improved earnings through cost-cutting and reorganization is echoed in quarterly earnings statements of nearly all companies reporting so far. But there is also a note of optimism about recovering markets, prices, and volumes. For instance, stresses Dow chairman and chief executive officer Frank Popoff, "While many of the challenges facing us will persist in 1994, Dow expects earnings to improve because of the company's ongoing efforts to enhance productivity, and as a result of recovering world economies and improved industry fundamentals.,, Ann Thayer
Inexpensive path makes key sugar intermediate Chemists at the Technical University of Berlin, Germany, have developed a simple method for making dihydroxyacetone phosphate (DHAP) from inexpensive starting materials, and reacting it at once in the same pot with aldehydes to make unusual sugar derivatives. Their technique for preparing and immediately using this key sugar intermediate may lead to progress in carbohydrate research—enabling preparation of new kinds of sugars, for example—and to advances in syntheses of single enantiomers of chiral drugs. Such advances are possible because there are four readily available aldolase enzymes that catalyze aldehyde condensations with DHAP to yield four different diastereoisomeric sugar configurations. Those four aldolases condense DHAP with D-glyceraldehyde or L-lactaldehyde to form D-fructose and the relatively rare D-tagatose, L-rhamnulose, and L-fuculose. These aldolases are efficient on a preparative scale, show a high degree of asymmetric induction in assembling two chiral centers at once, and have a wide tolerance of aldehyde substrate structures. This gives chemists a wide choice of configuration and aldehydes. Furthermore, the makeand-use feature of DHAP production avoids waste of stored DHAP, which is easily hydrolyzed. Indeed, the instability and high cost of DHAP have long been stumbling blocks to its use. For example, laboratory chemical supply houses price DHAFs diKthium salt at $240 per millimole. Organic chemistry professor Wolf-Dieter Fessner and graduate student Gudrun 8
JANUARY 31, 1994 C&EN
Sinerius report their work in the February issue of Angewandte Chemie [106, 217 (1994)]. They base their technique on the known oxidation of [.-glycerol 3-phosphate to DHAP by glycerol-3-phosphate oxidase (GPO). These materials are readily available at relatively low cost. Ordinarily, regeneration of a redox cofactor is a problem in redox reactions. Oxidases generally use as an oxidizing agent a small, dissociable redox molecule that is reduced in the process. But GPO uses as cofactor flavine-adenine dinucleotide, which is nondissociable and readily reoxidized by oxygen. Hydrogen peroxide is a coproduct. The Berlin team uses catalase to convert hydrogen peroxide to oxygen and water. So in their technique, Fessner and Sinerius combine L-glycerol 3-phosphate, an aldehyde, an aldolase, catalase, and GPO in oxygen-saturated water. They seal the flask under an oxygen atmosphere and put it on an automatic shaker. Besides making the four sugar diastereoisomers, they use glycerol phosphate analogs to make sugar analogs. Such analogs might function as enzyme inhibitors to treat disease. For example, substitution of glycerol phosphate by 3,4-dihydroxybutane-1 -phosphonate, N-2,3-dihydroxypropylphosphoramide, or 2,3-dihydroxypropane-1-thiol replaces the -OP03*"~ phosphate group with -CH2P032~, -NHP032~, or -SP03 , respectively. Stephen Stinson
Four configurations accessible via aldolases CH 2 OP0 3 2 -
CH 2 OP0 3 2 C=0 HO-OH -OH CH2OH D-Fructose 1-phosphate
C=0 HOHO-OH CH2OH D-Tagatose 1-phosphate
CH 2 OP0 3 2 -
CH 2 OP0 3 2 -
I
c=o
I
-OH -OH
-OH HOHOCH3 L-Rhamnulose 1-phosphate
HOCH3 L-Fuculose 1-phosphate
NIH seeks rules for indiistry-academia R&D Spurred by Congressional concern that U.S. taxpayers may not be reaping enough benefits from federally supported research, the National Institutes of Health has begun drafting guidelines for agreements between industry and universities that receive NIH funds. Last week in Bethesda, Md., NIH brought together officials from industry, research institutions, and NIH to hash over the complex issues at a forum on sponsored research agreements. NIH plans to draft guidelines based on the two-day forum's recommendations, and to present them to Congress by June, according to NIH director Harold E. Varmus. NIH's decision to develop guidelines was sparked by Congressional ire last year over a proposed agreement between Scripps Research Institute and Swiss-based Sandoz Pharmaceuticals Corp. Scripps, located in La Jolla, Calif., receives about $100 million a year in grants from NIH. In return for Sandoz funding of $300 million over 10 years, Scripps initially agreed to give the pharmaceutical company patent rights to all Scripps researchers' discoveries. The agreement was revised substantially after Rep. Ron Wyden (D.-Ore.) charged that Scripps was becoming a federally funded Sandoz laboratory. However, both Scripps and Sandoz still maintain that their original agreement was in keeping with the goals of the Bayh-Dole Act. That 1980 law aims to boost U.S. competitiveness by making it easier to commercialize federally funded inventions. It gives universities the right to patent the results of federally funded research and to license those patents to private companies. At last week's forum, Varmus explained that NIH convened the meeting to seek help in formulating criteria by which it can judge agreements between its grantees and industry. The discussion— enlivened by presentation of four fictional case studies—focused on a few key issues, including the scope and size of research agreements and research freedom. Tensions arise, notes Daryl A. (Sandy) Chamblee, NIH's acting deputy director for science policy and technology transfer, because of the need to encourage technology transfer, "while protecting the tax-
