Science Concentrates LAB SAFETY
Researcher loses arm in Hawaii explosion Incident involved mix of hydrogen, carbon dioxide, and oxygen gases
“Since 2008, when the project began, the process has been used almost daily and without incident.”
The explosion that injured Ekins-Coward on March 16 cracked the glass in the door of the lab where she was working. The Hawaii Occupational Safety & Health Division is investigating the incident. “UH will also be bringing outside experts for its own investigation,” university spokesman Daniel Meisenzahl told C&EN. “Leadership has made a commitment to make sure everything is done thoroughly and correctly.” Ekins-Coward is receiving workers’ compensation benefits, Meisenzahl added. HNEI has initiated a comprehensive safety review of all its laboratory operations, Taylor said. The building was found to be structurally sound and reopened on March 18, although the damaged lab remains closed.—JYLLIAN KEMSLEY
HO
TOTAL SYNTHESIS
Fast track to phorbol Nineteen-step enantioselective synthesis opens up avenues to previously inaccessible analogs For the first time, chemists have completed an enantioselective total synthesis of the complex natural product (+)-phorbol. And they did it with a route that requires only 19 steps. That’s a dramatic cut in chemical transformations from previous approaches, which took 40 to 52 steps to make a racemic mixture of the compound. Since its discovery more than 80 years ago, densely functionalized, polycyclic phorbol has intrigued both chemists and biologists. One source of phorbol is the sap of the manchineel tree, native to the Caribbean. The sap can cause skin to blister on contact. Certain derivatives, known as phorbol esters, encourage tumors to grow rapidly. But compounds in the phorbol family have also shown promise as immune-modulat-
6
C&EN | CEN.ACS.ORG | MARCH 28, 2016
ing, antiviral, and anticancer therapies. Phorbol and its derivatives are frequently made via semisynthesis, where a compound with much of phorbol’s skeleton is extracted from a natural source and then synthetically transformed. But this approach makes it impossible to make certain phorbol analogs. Seeking access to those compounds, Phil S. Baran, Shuhei Kawamura, and Hang Chu of Scripps Research Institute California and Jakob Felding of LEO Pharma developed a new enantioselective synthesis of phorbol (Nature 2016, DOI: 10.1038/nature17153). Baran, who led the project, notes that strategy was the key to this synthesis, as opposed to cutting-edge chemistry. “Everything that’s in this paper could have been done in 1978,” he says. The crucial insight,
OH
Baran notes, was to recognize that a key intermediH H ate his group had previously used to O OH make the anticancer OH compound ingenol (+)-Phorbol could be diverted to make phorbol—much like what happens biosynthetically. “The synthesis of phorbol, once considered a formidable if not impossible challenge, has attracted creative strategies from many laboratories,” comments Stanford University’s Paul Wender, whose lab reported the first racemic total synthesis of phorbol in 1989. The Baran lab now builds “impressively” on this body of earlier work and “cleverly introduces, among other noteworthy features, a C–H activation process that greatly enhances the step economy of this new route,” Wender adds. “One looks forward to ‘phorbol version 3.0’ that will surely be inspired by this and earlier research.”—BETHANY HALFORD
HO
ALLYSON BLAIR/HAWAII NEWS NOW
Postdoctoral researcher Thea Ekins-Cowhydrogen, carbon dioxide, and oxygen gases ard, 29, lost an arm and suffered other injufrom high-pressure cylinders into a lower ries in a lab explosion at the University of pressure container, said Brian Taylor, dean of Hawaii (UH), M¯anoa, on March 16. the School of Ocean & Earth Science & TechQueen’s Medical Center, where Eknology, during a March 17 news conference. ins-Coward was initially hospitalized, deThe mixture was to be used to feed bacteria. clined to release any informa“Since 2008, when the project tion about her condition as of began, the process has been C&EN press time. used almost daily and without Ekins-Coward was working incident,” Taylor said. for the Hawaii Natural Energy News media photos taken Institute (HNEI), which is outside the lab show cracked a research unit within UH. windows, walls, and ceiling HNEI researcher Jian Yu tiles, and a bent door. operates the lab in which the Ekins-Coward had received explosion happened. Yu’s general and lab-specific saferesearch program includes ty training, Environmental developing microbial processHealth & Safety Office Dies for producing biofuels and rector Roy Takekawa said at bioplastics from renewable Brian Taylor, dean, the news conference. The lab feedstocks. UH School of Ocean was last inspected in January At the time of the incident, & Earth Science & and passed all requirements, Ekins-Coward was combining Technology Takekawa said.
