Meetings Briefs

Below is a sampling of presentations made during the 1st European Chemistry Congress, held on Aug. 27-31, in Budapest.

University of Cambridge chemists have used a continuous-flow process to synthesize grossamide (shown), a lignanamide natural product that has been isolated from various fruit and seed sources. Lignanamides are a structurally diverse class of compounds that possess both cyclic and acyclic structures. Many of them have been shown to regulate biological functions in plants and microorganisms and are therefore of interest for potential pharmaceutical and agrochemical applications. "We have carried out the first stereoselective total synthesis of the compound, using a fully automated and scalable flow reactor," said Steven V. Ley, a chemistry professor at Cambridge. The reactor has a simple pumping arrangement with immobilized reagents packed in columns. It provides a rapid and flexible method for synthesizing up to gram quantities of such compounds on demand and avoids the need for extensive manual purification of the intermediates and final products. "We believe that these concepts will have an impact on the multistep synthesis of a much wider range of chemical substances," Ley said.

Gold chemistry is currently a hot topic in homogeneous catalysis, according to Antonio M. Echavarren of the Institute of Chemical Research of Catalonia, in Tarragona, Spain. Gold complexes exhibit "extraordinary" reactivity in the selective activation of alkynes in multifunctional molecules, he said. "Alkynophilic" catalysts allow complex organic transformations to be carried out under mild conditions, usually in a few minutes at room temperature. Recent work by Echavarren's group centers on the synthesis of cationic gold(I) complexes that catalyze the synthesis of structurally complex molecules from enynes, compounds with alkenyl and alkynyl functions. The group has shown, for example, that cationic gold(I) complexes catalyze the cyclization of enynes bearing an additional alkenyl or aryl group at the alkyne to give bi- or tricyclic ring systems. "We have also used the catalysts to perform the first intermolecular cyclopropanation reactions of enynes with alkenes," Echavarren said.

The amount of copper-based catalysts needed for making polymers by atom transfer radical polymerization (ATRP) has been reduced dramatically. ATRP is a simple way to incorporate functionality into polymers. It can be used for making a variety of polymers quantitatively in bulk, in solution, and in dispersed aqueous media, observed Krzysztof Matyjaszewski of Carnegie Mellon University. The process could be used to prepare advanced materials such as coatings, elastomers, adhesives, surfactants, dispersants, lubricants, and additives. But the transition-metal complexes used as catalysts have to be removed from the reaction mixture and preferably recycled. Matyjaszewski described new ATRP-initiating/catalytic systems that reduce the level of copper in the reaction mixture from around 10,000 ppm to less than 50 ppm. The systems contain environmentally friendly reducing agents, such as tin(II) octanoate, ascorbic acids, or sugars, which constantly transfer electrons to regenerate the ATRP Cu(I) activator complex from the Cu(II) species formed during the termination process.

An efficient delivery system for the controlled release of fragrances has been developed by chemists at flavor and fragrance manufacturer Firmenich in Geneva, Switzerland, and Louis Pasteur University in Strasbourg, France. "We have investigated the reversible formation of hydrazones to control the release of volatile organic molecules, a concept that may well find use in perfumery," Firmenich's Andreas Herrmann reported. The team showed that perfumery aldehydes and/or ketones combine reversibly with hydrazides in water to form dynamic mixtures of acylhydrazones. When exposed to a surface in contact with air, the perfumes evaporate and the equilibrium shifts toward the free hydrazide. "The gradual hydrolysis of the acylhydrazones in a dynamic mixture results in long-lasting fragrance release and therefore represents an efficient delivery system for the controlled release of volatile biologically active molecules," Herrmann explained. "Reversible covalent hydrazone formation could find general use in other areas such as the pharmaceutical and agrochemical industries."

An evolutionary strategy known as "iterative saturation mutagenesis" has been used to increase the thermostability of an enzyme without compromising its activity or enantioselectivity. The stability of proteins to heat is crucial when they are used as catalysts, as components in detergents, or as diagnostic tools, explained Manfred T. Reetz of the Max Planck Institute for Coal Research, in Mülheim, Germany. Thermophilic enzymes are characterized by higher degrees of rigidity caused by interactions—for example, salt bridges, hydrogen bonds, and π-π and hydrophobic interactions—at key positions in the protein that prevent unfolding during denaturation. Reetz and coworkers studied the lipase from Bacillus subtilis. They applied iterative cycles of saturation mutagenesis to those amino acids in the protein that exhibit pronounced degrees of thermal motion and thus flexibility. "We achieved an impressive enhancement of thermostability by screening fewer than 8,000 clones," Reetz noted. "However, because we have examined only one example so far, more work is necessary for generalization."