C&EN
news of the week SEPTEMBER 3, 2 0 0 7 EDITED BY WILLIAM G. SCHULZ & MELISSA KUHNELL
WHEN ORGANICS FAIL, TRY WATER NATURAL PRODUCTS: Ladder rjolyethers form readily from epoxides in water
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pathway, water proved to be an excellent solvent for the desired epoxideopening cascade. A lot of organic chem ists shy away from us ing water as a solvent, Jamison says, but its effects in this case were so profound that he and z Vilotij evic couldn't help 8 but take notice. < "Many synthetic Ϊ groups labored for years § in attempts to mimic Na- £ kanishi's ingenious poly- ? epoxide-zip-biosynthe- κ sis hypothesis," says K. g Barry Sharpless, a chem istry professor at Scripps Research Institute. "Now, Vilotijevic and Jamison have provided the marvelous insight that the desired cascade cyclizations work after all, provided they occur in water at neutral pH." "This is a nice piece of work indeed," adds K. C. Nicolaou, also a chemistry professor at Scripps. "The
Y REPLACING organic solvents with water, chemists have found a simple route to selective ly make ladder polyethers, including the build ing blocks of notorious toxins, via an epoxide-opening cascade reaction (Science 2007,3ΐγ, 1189). Complex ladder polyether natural products, so named for their runglike structure, are the active toxins found in the harmful algal blooms known as red tides. Red tides cause devastating ecological damage, so scientists hope that by studying this water-promoted cascade reaction, they will gain a better understanding Jamison (left) and Vilotijevic discuss of how and why these toxins form. ladder polyethers. The finding also offers a solution to what had been a long-standing puzzle for synthetic chemists. Twenty years ago, Koji Nakanishi, a chemistry professor at Columbia University, suggested that ladder polyether natural products arose biosynthetically from an elaborate cascade of epoxide-opening reactions B R E V E T O X I N Β A complex ladder that zip up the polyether structure. polyether toxin formed in red tides. "The Nakanishi hypothesis is very intellectu ally appealing," says Timothy F. Jamison, a Mas sachusetts Institute of Technology chemistry professor who spearheaded the current study. "It accounts for so much complexity in a very simple way." The only problem was that when organic chemists attempted this cascade in the lab, they found that Nakanishi's pathway was kinetically Η Η Η disfavored. Rather than forming the toxin's characteristic fused tetrahydropyrans, the C A S C A D E A tetrahydropyran moiety provides a template for the cascade reaction tended to open the epoxide epoxide-opening cascade in water. from the opposite side, generating a chain of Η Η Η Η spiro-tetrahydrofurans. To synthesize ladder H?0 polyethers via a cascade reaction, chemists had to use onerous directing groups—until now. Η Η Η Η Inspired by the elegance of Nakanishi's pro posed cascade, Jamison and graduate student Ivan Vilotijevic sought a transformation that would cascade reactions reported by the Jamison group are prove the hypothesis and provide a simplified route to amazing and shine new light on the possible biosyn thesis and chemical synthesis of the polyether marine the ladder polyether structure. They reasoned that a toxins, of which there are many. And once again, one tetrahydropyran within the molecule could provide a marvels at the special water effects on accelerating and template for the desired reaction. directing chemical reactions." He also notes that devel Then, after trying hundreds of reaction conditions, they discovered, much to their surprise, that while many oping reactions in water is a primary means of further ing green chemistry goals.—BETH ANY H ALFORD organic solvents usually favored the undesired reaction WWW.CEN-0NLINE.ORG
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SEPTEMBER 3, 2 0 0 7
