NEWS OF TH E WEEK
GETTING TO THE CORE IN ONE STEP DRUG DISCOVERY: Single-step annulation could ease access to key natural-product analogs
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FAMILY OF natural products called polyprenyl-
ated acylphloroglucinols (PPAPs) may not have a euphonious name, but they have been found to have promising biological effects, including anticancer and antidepressant properties. The drug discovery community would love to be able to evaluate close relatives of PPAPs, but they haven’t been able to do so because the naturally occurring substances and their analogs have been difficult to make synthetically. Now researchers have made an end run around that problem by synthesizing the core structure of PPAPs in a single step. The core structure can be decorated with diverse functional groups to conveniently make a wide range of PPAP analogs for drug discovery. Scores of PPAP natural products have been isolated over the years from a variety of plant sources. The most well-known PPAP is hyperforin, the primary active ingredient in the antidepressant medicinal herb St. John’s wort. The biological activities of PPAPs spring from their complex core, a bicyclic structure with three keto groups, three quaternary carbon centers, and several side chains. A number of PPAP total syntheses have been developed. Some are more efficient than others, but they are all fairly lengthy processes, and the natural products are not easy to derivatize to study variations on the
basic structure. So PPAP total synthesis has O not been practical for medicinal chemO istry use. Exemplifying the maxim “less is O more,” John A. Porco Jr. and coworkHO ers Alexander J. Grenning and Jonathan H. Boyce at Boston University (–)-Hyperforin have devised a technique O called “dearomative O OH O BocO conjunctive allylic annulation” to produce Pd catalyst the PPAP core strucOH ture in one step (J. Am. BocO Chem. Soc. 2014, DOI: 10.1021/ja5060302). Desoxyhumulone Conjunctive PPAP core A provisional patent substrate reagent structure on the technique has Circles = functional groups, Boc = tert-butyloxycarbonyl been filed. PalladiumThe method uses palladium catalysis to react arocatalyzed matic desoxyhumulone substrates with a “conjunctive” reaction combines (bond-forming) reagent to create a new ring, forming desoxyhumulone the PPAP bicyclic core structure. It yields grams of matesubstrate and rial, and the product can be diversified for drug testing. bond-forming The technique “represents a significant advance in “conjunctive” reagent to form the systematic, practical, and rapid production of a large the core structure array of PPAP analogs,” comments PPAP-synthesis speof PPAPs such cialist David Yu-Kai Chen of Seoul National University, as hyperforin in South Korea. It “will facilitate more in-depth inves(top), the active tigations and understanding of PPAPs, both chemically ingredient in St. and more importantly as potential therapeutic agents.” John’s wort. The core structure’s potential as a building block for medicinal chemistry makes the study a breakthrough in the field, says another PPAP expert, Bernd J. Plietker of the University of Stuttgart, in Germany. “I would like to have had the same idea, but I didn’t, so I have to give John Porco the credit.”—STU BORMAN
SCIENTIFIC PUBLISHING ACS Biomaterials Science & Engineering will launch in January 2015
ALIX C. K APLAN
The American Chemical Society plans to begin publishing a new journal, ACS Biomaterials Science & Engineering, with the first full issue due for release in January 2015. David L. Kaplan, professor and chair of the Kaplan department of biomedical engineering at Tufts University, in Medford, Mass., will serve as the journal’s inaugural editorin-chief. The monthly, onlineonly journal will focus on research in the rapidly burgeoning field of biomaterials, which involves the study of engineered
or naturally derived materials that interact with biological systems. Topics will include modeling and informatics tools for biomaterials; new biomaterials; bioinspired and biomimetic approaches to developing biomaterials; biomaterial interfaces, biology, and health; and biomaterials manufacturing and technology. The launch of “this new journal is timely as it reflects the tremendous growth in the field of biomaterials over the past decade,” Kaplan says. “ACS Biomaterials Sci-
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ence & Engineering will provide scientists from many disciplines with a publishing outlet for their work at the interface of biology and materials science and engineering,” says Susan King, senior vice president of the Journals Publishing Group at ACS, which publishes C&EN. Kaplan earned a B.S. in biology from the University at Albany, SUNY, in 1975 and a Ph.D. in biology and biochemistry from Syracuse University and SUNY Syracuse in 1978. His research focuses on biopolymer engineering, with an emphasis on biomaterials engineering, tissue engineering, and regenerative medicine. The journal will begin accepting manuscript submissions in September.— SUSAN AINSWORTH
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