N EWS OF THE W EEK
BRYOSTATIN, FASTER ORGANIC CHEMISTRY: Highly selective
catalysis dramatically reduces steps to multiring structure
A
22-membered ring intermediate. This marks the first time that such a large ring structure has been made by this type of carbon-carbon bond-forming reaction, writes University of Montreal chemist André B. Charette in a commentary accompanying the report. The Pd-catalyzed reaction allowed the team to avoid using alkene metathesis to make the large ring, a strategy that had failed them in the past. It also set the stage for a gold-catalyzed reaction that harnessed alkyne reactivity to selectively form a six-membered dihydropyran ring instead of a typically easier to form five-membered ring. The team now plans to use the route to make additional bryostatins, as well as analogs.
LKYNES’ UNIQUE EMBRACE of transitionmetal catalysts has enabled the shortest route yet to the bryostatins, marine natural products with promising anticancer and memory-enhancing properties. The synthetic advance, reported in Nature (2008, 456, 485), could allow a more thorough evaluation of the compounds’ biomedical potential. THRIFTY SYNTHESIS Because only small amounts of the A palladium-catalyzed union of two alkynes selectively forms bryostatin 16’s large ring. bryostatins are available, investigations of their therapeutic activity have been HO CH3O hampered. Three previous total syntheses CH3O O CH3O OH of bryostatin family members have been O O O O reported, but they required lengthy seO O O OH quences of at least 40 consecutive synthetOTES O ic steps. Now, chemists Guangbin Dong O and Barry M. Trost of Stanford University O O O have developed a route to a bryostatin that HO clocks in at 26 steps. OH To make bryostatin 16, Dong and Trost OTBS OCH CH3O 3 implemented a series of transition-metalcatalyzed reactions, each of which relies O O on the metal’s selective interaction with TES = triethylsilyl an alkyne over other functional groups. TBS = tert-butyldimethylsilyl Bryostatin 16 “The alkynes play a critical role in allowing us to reduce the number of steps” by, “This is a monumental piece of work,” says organofor instance, reducing the need for protecting groups, metallic chemist Alois Fürstner, a director at the Max Trost explains. Furthermore, the key reactions adhere to Trost’s philosophy of atom economy, in which all the Planck Institute for Coal Research, in Mülheim an der Ruhr, Germany. The team’s creative handling of atoms in the reactants wind up in the products. delicate selectivity issues makes the synthesis highly In a crucial step, the Stanford team used a pallaimpressive, he adds.—CARMEN DRAHL dium-catalyzed coupling of two alkynes to form a
CLIMATE CHANGE UN meeting in Poland lays groundwork for 2009 talks The United Nations’ climate-change talks this week through Dec. 12 in Pozna´ n, Poland, will set the stage for intense negotiations next year that are expected to culminate with a new treaty to lower global emissions of greenhouse gases. Observers, however, expect the meeting to produce few concrete results. Governments “won’t negotiate substance” in Pozna´ n, says Sen. John F. Kerry (D-Mass.), who leads a congressional delegation to the meeting. In January 2009, Kerry will assume the helm of the Senate Foreign Relations Committee
as the current chairman, Sen. Joseph R. Biden Jr. (D-Del.), will be sworn in as vice president. The sagging global economy will influence the Pozna´ n talks and the negotiations on a new climate accord, which is supposed to be completed at a December 2009 meeting in Copenhagen. “Economic realities may affect short-term goals” for global emissions reductions, Kerry says. One tangible outcome expected from the Pozna´ n meeting is a deal to reduce deforestation in developing countries,
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says Angela Anderson, director of Pew Environment Group’s International Global Warming Campaign. Governments will also sketch broad goals for the new climate treaty, leaving the details for next year’s negotiations, she adds. The success of the 2009 talks hinges on whether developing countries, especially China and India, agree to control emissions, says Frank V. Maisano, an energy specialist at Bracewell & Giuliani who represents utilities, refiners, and wind-power developers.—CHERYL HOGUE
