NEWS OF THE WEEK
ELUSIVE NATURAL PRODUCT IS SYNTHESIZED ENANTIOSELECTIVE SYNTHESIS:
Kinamycin C, antibiotic with unusual diazo group, is created from scratch
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INAMYCIN C, a bioactive natural product whose structure was misinterpreted when it was discovered in the early 1970s and wasn't corrected until over two decades later, has succumbed to total synthesis (J. Am. Chem. Soc, DOI: 10.1021/ jao6662iv). Kinamycin G is one of several compounds in the kinamycin family with strong antibiotic and anticancer activity. Its enantioselective total synthesis, by graduate student Xiaoguang Lei and chemistry professor John A. Porco Jr. of Boston University, could facilitate the creation of interesting variants for drug discovery and other applications. The work also represents a potential first step toward the assembly of related dimeric compounds, the lomaiviticins, whose synthesis is being ardently pursued by several groups. A key step in kinamycin G's synthesis was the use of an asymmetric nucleophilic epoxidation, developed earlier by Porco's group, to establish the correct configuration and stereochemistry of a cyclic fragment that became the natural product's highly oxygenated D ring. The compound's diazo group, which also presented a great synthetic challenge because of its high reactivity, was installed very late in the synthesis. The presence in kinamycin G of a diazo group, instead of what had earlier been believed to be an Ncyano group, was discovered independently by two research teams in 1994. Apart from the 1996 synthesis of abiosynthetic precursor, progress on the synthesis of
kinamycin C "has been relatively slow," says associate professor of chemistry Gary Dmitrienko of the University of Waterloo, Ontario, who led one of the teams that recognized the compound's diazo group. The stereocontrolled construction of the D ring and the problem of introducing the delicate diazo group have proven to be nontrivial issues, Dmitrienko says. This first total synthesis in the kinamycin series "is a promising initial step toward the generation of analogs of the kinamycins to optimize their potential therapeutic properties and to probe their mode of action," which recent biological and biochemical studies suggest is unlike that of other known antibiotics. The kinamycins are already Lei accessible by fermentation, so Porco the new synthesis is not necessarily needed to produce them, says Guy T. OAc AcO Carter, assistant vice president of chemical technologies in Chemical & Screening Sciences at Wyeth Pharmaceuticals, Pearl River, N.Y. "Nevertheless, the total synthesis would allow for modifications to be made so you could probe structure-activity relationships OH 0 more easily than would be possible with a Ac = acetyl biosynthetic approach. And people who are trying to synthesize the lomaiviticins will Kinamycin C benefit from this study" because the lomaiviticins contain kinamycin-like units. "This is a beautifully instructive synthesis of a chal lenging natural product that has been hotly pursued by several groups over the past decade," comments associate professor of chemistry Phil S. Baran of Scripps Research Institute. It "will pave the way for syntheses of other members of the family and allow access to kinamycin analogs inaccessible from nature."—STU BORMAN
MEDIA SPOTLIGHT Panel debates whether science gets a fair shake A panel of science writers met at Columbia University in New York City late last month to examine challenges that the news media face in getting the science right for a story. Aimed at answering one central question—Does science get a fair shake in the press?—the event attracted about 4 0 people from the media and science communities. Discussion moderator John Rennie, editor-in-chief of Scientific American, said the news media's job is to explain the science behind current issues. Because the press is frequently unsuc-
cessful in doing so, he asked panelists to consider some of the systemic problems they see with press coverage of science. Science is "about quantifying and managing uncertainty" Rennie said, whereas journalists "want clear statements." Panelists Cornelia Dean, science writer at the New York Times, and Robert Krulwich, a correspondent for ABC News, discussed the problems they've encountered in trying to explain complex problems in clear terms. Krulwich noted that the public's desire for short yes-or-no answers to short questions presents a paradox for
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people who write about complex issues. Scientific American, whose articles explain current science and technology developments, sponsored the event along with the American Chemistry Council, a trade association concerned about the public's perception of chemistry. Thomas Metzger, ACC marketing and public relations director, said the association plans to distribute a video of the event to member companies that have had problems presenting science-based arguments on chemistry-related issues to a skeptical public—MARC REISCH
