n e w s of t h e w e e k quantum mechanical calculation of the ab solute stereochemistry of a simple mole cule with one stereocenter, CHBrCIF (C&EN, April 21, 1997, page 32). Dealing with a complex molecule like hennoxazole, however, is another story, Beratan says. The group calculated its stereochemistry by dividing the mole cule into three more manageable pieces that f a bold theoretical approach pans out, contained fewer stereochemists could be saved years of inten centers, determining sive labor sorting out the correct ste the fragments' rotations, reoisomers of complex natural products. then "reassembling" the University of Pittsburgh chemistry pro molecule. If such a tool fessors David Beratan and Peter Wipf and had been available earli their graduate student Rama K. Kondru er, Wipf s group would have correctly determined the absolute have been spared more stereochemistry of the marine natural than a year's work. product hennoxazole by computational Although the re methods (J. Am. Chem. Soc, published search is "a tribute to Feb. 24 ASAP, http://pubs.acs.org/ the growing [ability] of journals/jacsat). computational chemis Provided people understand how to Beratan (left), Wipf, and Kondru worked out theory for try to direct research," apply the theory, "I think it's going to be determining stereochemistry of natural products. generalizing the method a potentially very powerful method," says Columbia University chemistry pro when it passes through a sample. How will take a lot of work, notes University fessor Koji Nakanishi, an expert on natu ever, there are no clear-cut correlations of California, San Diego, chemistry pro fessor Jay S. Siegel. ral products structure. between rotation angle and structure. The Pittsburgh group is now trying When chemists isolate or synthesize a Several years ago, Wipf s lab per complicated natural product, they can formed a total synthesis of hennoxazole, the same technique on another mole determine its basic structure with tech a potential antiviral agent. He and his col cule, also a marine natural product, but niques such as nuclear magnetic reso leagues then spent the better part of two one with unknown stereochemistry. "The real potential [of our theory] be nance spectroscopy and X-ray crystallog years plowing through four total synthe raphy. But nailing down a molecule's ab ses before unambiguously determining comes apparent for molecules with so solute stereochemistry is more difficult, the correct stereoisomer. It was an intel many stereocenters you would have 50 because most of the physical properties lectual challenge, Wipf says, "to con to 100 potential synthesis targets, and of stereoisomers are identical, and the vince one of my physical chemist col there's no way to figure out which one more stereocenters a molecule has, the leagues that there would be a tremen to make," Wipf says. "It's actually very more isomers there are to distinguish dous advantage to natural product exciting." Elizabeth Wilson among. chemists if we could identify links be Chemists learn early that one proper tween structure and optical rotation." So ty that distinguishes enantiomers is opti Beratan took up the challenge. cal rotation, in which plane-polarized Since the dawn of quantum mechan light is rotated through a certain angle ics in the 1920s, a theoretical framework for determining a — — — — molecule's optical rotation angle has ex Moving to create "one of the top suppli Fragments simplify theoretical calculations isted. But throughout ers to the life sciences industry," Dutch the 1960s and 70s, chemical company DSM will acquire OH computers and algo compatriot firm Royal Gist-Brocades, one rithms weren't up to of the leading enzyme and biotechnology the task, Beratan ex specialists worldwide. The merger will create a company with plains. And in more recent years, atten annual sales of almost $7.4 billion, of tion has been fo which about 25% will come from sales of Hennoxazole A cused on other chiral products for pharmaceuticals, foodstuffs, and cattle feed. DSM is essentially paying OH optical properties. OCHo But last year, Pra $1.33 billion to acquire Gist-Brocades and sad L. Polavarapu, is exchanging one-sixth share of stock for ^O chemistry professor each share of Gist-Brocades. OH Ξ XT Ο CH30 H For DSM, the rationale is clear. "DSM's at Vanderbilt Universi ty in Nashville, Term., antibiotics activities will be strongly ex Fragment 1 Fragment 2 Fragment 3 performed the first panded, and a food-additives segment will
LEFT OR RIGHT?
Theory could quickly sort out stereochemistry of natural products
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Dutch merger yields life sciences giant
MARCH 2, 1998 C&EN 9
