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CHEMISTRY
90% purity in only one day. Key steps include trapping previously prepared 4-(2-azidoethyl)phenol with a polymer-supported phosphine on a column and subsequently coupling it with 3,4-dimethoxybenzaldehyde, which is prepared in a separate channel. The resulting imine intermediate is sequentially converted to an OMBINING THE BEST TECHeconomic gains are possible by amide in steps that include changniques for automated chem- reducing solvent use, energy con- ing solvents and a palladium-mediistry with the green chem- sumption, waste generation, labor ated hydrogénation. The hydrogéistry concept of consolidating or costs, and time. nation takes place in a flow-through eliminating reaction steps, Steven "This is really exciting research," unit developed by Thaïes NanoV. Ley and coworkers at the Uni- commentsjohn C. Warner, director technology, Budapest, Hungary. versity of Cambridge have accom- of the Center for Green Chemistry In the final stages, the third ring plished the first multistep synthesis at the University ofMassachusetts, of oxomaritidine is formed and ELEGANT FLOW of a complex natural product in a Lowell "We have traditionalry tried the amide is cleaved, promoting Cambridge postdoc continuous-flow reaction (Chem. to compartmentalize various reac- a bridging 1,4-addition to give the Jon Deeley works Commun., published online Feb. tion stages. Ley's end product. with Ley's polymer15, dx.doi.org/10.1039/b600382f). group has been "We can envis- supported reagents Their intensified process for syn- able to escape these age many excit- in a Syrris flowthesizing the widely studied alkaloid confines and deing opportunities reaction system. CH30 oxomaritidine maybe a milestone sign a process that for machine profor the future ofpharmaceutical and elegantly strings duction of chemifine chemicals production. the steps together. cal entities using Oxomaritidine these on-demand Ley's group is known for its I see this work as techniques," Ley polymer-supported reagents, a declaration that catalysts, and cleanup scavengers complex synthetic schemes in says. "Processes can be scaled that are used in the synthesis and general can be redesigned for flow down or scaled up, creating possibilities for the preparation and purification of compounds to cre- processing." ate combinatorial libraries and The Cambridge process, which online screening of compounds individual compounds in one-pot involves seven synthetic steps, can for biological or materials properreactions. The work has evolved to generate gram quantities of oxo- ties, or for their efficient producinclude microfluidic glass reaction maritidine in 40% overall yield and tion."—STEVE RITTER chips and small columns containing the immobilized reagents that V A C C I N E S can be used in series to carry out seamless multistep reactions. In late 2004, Ley began a collaboration with Syrris, a U.K.stockpile of bulk H5N1 vaccine for the U.S. Deovernments in Europe are building stockbased microreactor company, to partment of Health & Human Services. piles of vaccine to protect people from the explore multistep syntheses using avian influenza virus, known as H5N1, folLast week, Sanofi Pasteur said it had supplied one of the company's systems. This lowing its spread into Europe and Africa from the Italian government with a stock of bulk H5N1 union led to the successful proce- Asia. vaccine that could be formulated into 185,000 dure to make oxomaritidine. doses. Sanofi notes that it earlier reached supply The virus has been identified in scores of dead The benefits of multistep con- wild birds, particularly swans and ducks, across agreements with the U.S., Australian, and French tinuous reactors employing im- Europe; in domesticated turkeys in France; and governments. mobilized reagents and microflu- in a dead cat thought to have eaten infected wild Meanwhile, vaccination of domestic poultry has idic devices are considerable. The birds on the Baltic Coast of Germany. To date, no begun in France. Akzo Nobel subsidiary Intervet is reactors allow better control over occurrence of bird flu in humans in the region has supplying the French Ministry of Agriculture with synthesis conditions, make more been reported. But public health officials are takvaccine for domestic poultry in regions at risk efficient use of starting materials, ing no chances. from migrating birds. Additionally, Intervet will can readily recycle chemicals, and supply at least 30 million doses of vaccine against The U.K. government recently said it will spend are able to circumvent or elimi- a total of nearly $60 million on 3.5 million doses of the virus strain known as H5N2, which the comnate isolation and purification the vaccine from Chiron and 2 million doses of the pany says is closely enough related to the avian flu steps common in batch process- vaccine from Baxter International for stockpiles. virus to induce protection in vaccinated poultry.— ing. Overall environmental and Chiron has already netted a contract to build a PATRICIA SHORT
NATURAL PRODUCT SYNTHESIS ON THE FLY
Multistep continuous reaction shows the power of automated flow synthesis
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Europeans Stock Up In Event Of Bird Flu
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