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ACS 1995 National Award Winners
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ollowing are vignettes of the Arthur C. Cope Award winner and 10 recip ients of Arthur C. Cope Scholar Awards. The winners will receive their awards during the fall 1995 210th ACS na tional meeting in Chicago at the Arthur C. Cope Symposium organized by the ACS Di vision of Organic Chemistry. These awards recognize and encourage excellence in organic chemistry. The Cope Award consists of a medal, a personal cash prize, and an unrestricted research grant to be assigned by the recipient to any univer sity or nonprofit institution. The scholar awards consist of a certificate and an unre stricted research grant. Each recipient is re quired to deliver a lecture at the Arthur C. Cope Symposium.
Arthur C. Cope Award GEORGE M. WHITESIDES, who is Mallinckrodt Professor of Chemistry at Harvard University, has made impor tant and original contributions to the mechanisms of organometallic reactions, to the study of dynamic stereochemical problems by nuclear magnetic resonance spectroscopy (NMR), to the use and mechanisms of reaction organometallic reagents, to the nature of heterogeneous reactions, to the strategy of self-assembly for the preparation of molecules in orga nized monolayers on surfaces and in solution, to the exploitation and use of enzymes in synthesis, to microlithography, and to drug design. Whitesides recognized early the power of NMR for the study of dynam ic problems and stereochemistry. He carried out the first dynamic line-shape analysis on a complex coupled-spin system, and he provided the first ex perimental demonstration for the mechanism of pseudorotation of mole cules such as SF4 and (CH3)2NPF4 by analyzing their spectra. Whitesides in vented the chiral europium shift re agent, which has become a widely used method for chiral perturbation in the analysis of enantiomeric purity. He has also studied a range of ele mentary transition-metal organometallic reactions that are representative of those
that occur in homogeneous catalysis us ing organoplatinum and organocopper compounds. Whitesides demonstrated for the first time the activation of carbonhydrogen bonds by homogeneous Pt[0] complexes, and he was the first to syn thesize a characterized transition-metal metallocycle and to demonstrate the rel evance of metallocycles in catalysis. Along with C. P. Casey, he has made critical contributions to the development of synthetic applications of organocuprates in organic chemistry. In organic surface chemistry, Whitesides, according to a colleague, "is once again bringing rationality to a field that has for so long been largely phenomenological." He has focused on the develop ment of characterized surfaces with a well-defined organic component on a definable solid surface. He is doing fun damental work on, for example, self-as sembled monolayer (SAM) films assem bled on gold and silicon. New methods are being developed to improve the char acterization of the solid-liquid interface and to apply these SAMs in mammalian cell culture, lithography, and optics. The past several years have witnessed Whitesides' enormously successful foray into the use of enzymes as reagents for large-scale synthesis. Typically, Whitesides has identified and sequentially at-
Whitesides
tacked the fundamental problems in this area: cofactor regeneration, enzyme sta bilization, and enzyme immobilization. In cofactor regeneration, Whitesides achieved remarkably high turnover numbers by in situ regeneration meth ods. In the stabilization and immobiliza tion area, he developed novel polymers that have extended the useful lifetimes of enzyme catalysts by many orders of magnitude. Perhaps his most dramatic achieve ment is in the area of multienzyme systems. Whitesides (with Chi-Huey Wong) was the first to demonstrate the practical utility of the Leloir pathway for the synthesis of complex carbohydrates. The burgeoning field of carbohydrate cell-surface antigens had only classical chemistry to underpin it. Whitesides has made superb contributions to enzyme assisted synthesis of standard building blocks for C8 and C9 sugars and their as sembly into oligosaccharides and to the design of polyvalent drugs targeted to viral surfaces. Another colleague summarizes, 'The only one Γ can remember who made such important contributions to as wide a range of organic chemistry was Arthur C. Cope/' Whitesides received an A.B. degree from Harvard in 1960 and a Ph.D. de gree from California Institute of Tech nology (with John D. Roberts) in 1964. He was a member of the faculty of Massachusetts Institute of Technology from 1963 to 1982, before he joined the faculty at Harvard. He received an Alfred P. Sloan fel lowship in 1968, the ACS Award in Pure Chemistry in 1975, the Harrison Howe Award of the ACS Rochester Section in 1979, an Alumni Distin guished Service Award from Caltech in 1980, the Remsen Award of the ACS Maryland Section in 1983, an Arthur C. Cope Scholar Award in 1989, and the James Flack Norris Award in Physical Organic Chemistry in 1994. He is a member of the American Academy of Arts & Sciences and the National Acad emy of Sciences and a fellow of the American Association for the Advance ment of Science. NOVEMBER 14,1994 C&EN
49
AWARDS
Arthur C Cope Scholar Awards STEVEN G. BOXER, a chemistry professor at Stanford University, works at the interface of biophysical and bioorganic chemistry. In the words of one colleague, Boxer "has made major contributions to our understanding of photosynthesis, protein electrostatics, and dynamics/7 In his research, Boxer has focused on two broad biological problems: The mechanism of the early electron-transfer events in photosynthetic reaction centers and the mechanisms by which ligands bind to heme proteins and what regulates their binding affinities. Although these problems may seem unrelated, Boxer connected them several years ago when he inserted chlorophyll into the heme-binding pocket of myoglobin in place of the heme. Additionally, much of Boxer's work on myoglobin has been concerned with electrostatic interactions between functional groups in proteins and the surrounding protein matrix, with the matrix viewed as a solvent. Such electrostatic interactions also are central to understanding electron transfer in photosynthesis. Boxer's research on photosynthetic reaction centers primarily concerns the earliest light-driven steps. The key issues his work has addressed are understanding what is special about the dimeric pair of chlorophyll molecules whose excited state initiates photosynthesis; the mechanism of the initial, ultrafast, long-distance electron-transfer reaction; and the origin of unidirectional electron transfer in the photosynthetic reaction center. Applied electric fields have proven to be useful in all aspects of this work, both as a spectroscopic tool and as a method for manipulating the rates of electrontransfer reactions. Using these techniques, Boxer has discovered that the special pair dimer is highly polarizable, meaning that it is very sensitive to local electrostatic perturbations. This result has been corroborated by site-directed mutagenesis experiments. Boxer also has discovered that the initial electron-transfer reaction likely occurs in a single step over a long distance, and that, despite the high structural symmetry of the reaction center, the local dielectric properties are asymmetric, contributing to functional asymmetry. Boxer's work on heme proteins be50
NOVEMBER 14,1994 C&EN
gan with the first cloning and expression of myoglobin in Escherichia coli 10 years ago. This has led to many studies employing site-directed mutagenesis to probe electrostatic interactions, ligand binding, and selective recognition. Recently, the research has included the construction of a random library of single amino acid mutations in myoglobin and develBoxer Danheiser opment of automated technology for screening large libraries and [2 + 2] cycloadditions. Later, they of mutant proteins to discover novel li- used vinylketenes to build eight-membered rings and highly substituted cargand binding pathways. The latest development on heme pro- boaromatic and heteroaromatic comteins in Boxer's lab involves the creation pounds. As one colleague puts it: "These of cavities within myoglobin that permit reactions have considerable charm. They the incorporation of exogenous organic involve ingenious cascades of pericyclic molecules as ligands to the heme iron. reactions to generate ring systems that His group has shown that the occupants are difficult to construct by conventional of these cavities can be replaced by an techniques." The [4 + 1] annulation strategy for cyenormous range of ligands, many of which bear no resemblance to natural clopentene synthesis is another outamino acid side chains. By combining standing result of Danheiser's research. the structural framework of the natural The method is highly stereoselective and protein with unnatural occupants of involves a remarkable process discovthese functional cavities, it is possible to ered in his laboratory: anion-accelerated generate an enormous diversity of novel vinylcyclopropane rearrangement. Recently, unusual cyclizations and protein function. This approach is likely to have widespread use as a means for cycloaddition reactions of conjugated acetylenes and aliènes have been the modulating protein function. focus of Danheiser's creative energies. RICK L. DANHEISER is a master of The first fruit of work in this area is a synthetic strategy. His forte is annula- novel cycloaddition strategy involving tion—the creation of cyclic systems by conjugated enynes. Like other synthecombining noncyclic precursors. And he ses he and his team have crafted, these wields his skills to design "crisp" total new reactions have "mechanistic elesyntheses of natural products that, ac- gance," as well as obvious strategic cording to a peer, are "extremely effi- utility. His methods work well, as amply cient as well as aesthetically pleasing." The "Danheiser annulation" is but demonstrated by efficient and elegant one contribution of his productive re- total syntheses of various natural prodsearch group at Massachusetts Institute ucts including anatoxin a, mycophenolof Technology. The reaction bearing his ic acid, maesanin, salvilenone, and sevname uses organosilanes to gain access eral diterpenoid quinones derived from to five-membered ring systems in a the Chinese traditional medicine called highly stereoselective manner. Al- dan shen. Danheiser received an A.B. degree though conceived initially for cyclopentane and cyclopentene derivatives, (summa cum laude) from Columbia the reaction has been used to construct University in 1972 and M.A. and Ph.D. heterocycles and aromatic systems, in- degrees from Harvard University in 1975 and 1978, respectively. In 1978, he cluding azulenes. Danheiser's team at MIT constantly joined MIT, where he is currently proseeks new approaches to the total syn- fessor of chemistry. In 1985, Danheiser received the Stuart theses of complex natural products. His group pioneered the use of vinylketenes, Pharmaceuticals Award for Excellence initially putting these molecules to work in Chemical Research. He has been an in elegant Diels-Alder-type reactions Arthur P. Sloan fellow, a Japan Society
Jung
Katz
for the Promotion of Science fellow, and a fellow of the American Association for the Advancement of Science. Along with writing more than 50 publications, he holds a patent for a method for synthe sizing β-lactones and alkenes. He serves on the editorial board of the "Encyclopedia of Reagents for Or ganic Syntheses" and is a member of the American Chemical Society, the British Royal Society of Chemistry, and the Swiss Chemical Society. A wide range of research interests characterizes the career of MICHAEL E. JUNG, professor of chemistry at the University of California, Los Angeles. Early work led him to invent trimethylsilyl iodide as a useful reagent in or ganic synthesis for applications ranging from the dealkylative cleavage of ethers, esters, and urethanes, among others, or the activation in organometallic addi tions to carbonyls, and to the dehydra tion and rearrangement of oximes. Later, Jung investigated three-carbon annula tions, anionic oxy-Cope rearrangements on aromatic systems, and inter- and in tramolecular Diels-Alder reactions. He has also devised methods to synthesize a diverse group of natural products, in cluding seychellene, podophyllotoxin, gilvocarcin, isodityrosine, carbovir, AZT, and the aplysiapyranoids. His work on Diels-Alder reactions is considered particularly significant. He demonstrated that the long-known effect of gem disubstitution on the rate of cyclization reactions is largely—and in some cases, entirely—due to a lowering of the enthalpy of activation, rather than to a change in bond angles, as the basic Thorpe-Ingold premise held. This dem onstration has led, in turn, to the subse quent discovery by Jung that gem oxy gen substituents, as in ketals, produce a much larger acceleration of ring forma
Leonard
tion, as in the intramolecular Diels-Alder reaction, for example, than alkyl groups. Hence, the gem-dialkoxy effect rep resents a new potential for cyclization reactions in general. As Jung has dem onstrated, a cyclobutanone ketal forms surprisingly readily in a radical cycliza tion process. Other Diels-Alder work has shown that the reaction is greatly accelerated by polar solvents when the link between diene and dienophile is an ester group—in contrast to the gen eral observation that classical Diels-Al der reactions are essentially unaffected by solvent polarity. Jung has received a number of honors and awards throughout his career, in cluding the Inaugural Gold Shield Facul ty Award; the Herbert Newby McCoy Award, the Hanson-Dow Teaching Award, a University Distinguished Teaching Award, and the Glenn T. Seaborg Award, all from UCLA; a FulbrightHays Grant; a Sloan Foundation Fellow ship; and a Camille & Henry Dreyfus Foundation Teacher-Scholar Award. He was Fujii-Ohtsuka Professor at the Uni versity of Tokushima, Japan, in 1991. Jung received a B.A. degree in 1969 from Rice University and a Ph.D. de gree from Columbia University in 1973. He was a North Atlantic Treaty Orga nization postdoctoral fellow at the Swiss Federal Institute of Technology, Zurich, 1973-74, and visiting professor at the University of Paris VI (Pierre & Marie Curie), 1980-81. According to a colleague, THOMAS J. KATZ, professor of chemistry at Co lumbia University, has made "truly orig inal, imaginative, uniquely clever, and significant contributions to fundamental science in the areas of mechanistic and synthetic organic and organometallic chemistry/' A perusal of his publications reveals the breadth of his research.
Katz was the first to recognize, syn thesize, and characterize the cyclooctatetraene dianion and the cyclononatetraenyl anion, aromatic nuclei in which 10 π electrons are delocalized in a ring. Extensions were syntheses of the pentalene dianion, the first cyclobutenyl cations, molecules with bridging phos phorus atoms, and molecules in which two metal atoms are sandwiched be tween a pair of planar aromatic rings. The outstanding character of Katz's synthetic ability is seen in his methods for the synthesis of the three valence iso mers of benzene. His synthesis of benzvalene has made this material abundant, whereas it was previously available only in minuscule amounts. His synthesis of prismane is still the only synthesis known for that remarkable structure. Another example is the synthesis of a stable pentaalkylphosphorane, the first molecule in which five alkyl groups are attached to phosphorus. In addition to his contributions to or ganic synthesis, Katz has made impor tant contributions to organometallic chemistry and the understanding of chemical mechanisms. He discovered that rhodium catalyzes cycloaddition reactions and showed how by a new technique now called the induced iso tope effect. His analyses of the mecha nism of the olefin metathesis reaction ex plained why terminal olefins undergo metatheses only sluggishly and led to the first preparation by olefin metathesis of translationally invariant polyisoprene and other poly(trisubstituted olefins). Katz also reported the first general preparation of highly stereospecific polyalkenamers, the discovery that metal-carbenes initiate polymerization of acetylenes and metathesis of olefins, and the discovery that acetylenes induce ole fins to metathesize. In still another area, Katz reported the synthesis of the first helical metallocene and the first helical metallocene oligomer, by processes that use one asymmetric center to control the direc tion in which the helix winds. Katz received a B.A. degree in chem istry from the University of Wisconsin in 1956 and M.A. and Ph.D. degrees from Harvard University in 1957 and 1959, r e spectively. He was an Alfred P. Sloan fellow (1962-66) and a John Simon Guggenheim Memorial Foundation fel low (1967-68), and in 1993, he was elect ed as a fellow of the American Academy of Arts & Sciences. NOVEMBER 14,1994 C&EN
51
AWARDS
NELSON J. LEONARD has pioneered bioorganic chemistry for about 35 years and is a primary contributor to fundamental knowledge of the chemistry of nitrogen-containing organic molecules. In the past few years, he has applied synthetic methods to compounds important to biochemistry and plant physiology. Leonard is currently faculty associate at California Institute of Technology and also R. C. Fuson Professor Emeritus of Chemistry and professor emeritus of biochemistry at the University of Illinois, Urbana-Champaign. His recent work has focused on chemical, spatial, fluorescent, and dimensional probes of enzyme-coenzyme interactions and of nucleic acid structure and function, as well as the cytokinins that facilitate cell growth, cell division, and cell differentiation. Leonard's fundamental investigation of the reaction of chloroacetaldehyde with nucleic acid components is just one example of his pioneering research. The work resulted in the production of fluorescent products from adenine and guanine units. The products, isolated from liver DNA or RNA, can now be used to detect human exposure to the industrial carcinogen vinyl chloride as well as to chloroacetaldehyde. Leonard has also investigated tris-striazine which consists of a coplanar arrangement of three fused s-triazine rings. Leonard reported the synthesis, chemical behavior, and spectroscopic and theoretical probes of valence orbital structure of this fundamental N-aromatic ring system in 1984, a structure first proposed by Linus Pauling in 1937. Yet another example of his work is the development of heterocyclic ring systems with covalently linked cross sections. These have molecular architecture similar to the hydrogen-bonded base pairs of DNA and RNA and are potential candidates for incorporation into various biological systems. The core heterocyclic ring system is based on 1,3,4,6-tetraazapentalene. According to a colleague, Leonard has not only been a scientist of the highest reputation in organic chemistry but also "an ambassador of science on an international level." He has, for example, been actively involved with the International Union of Pure & Applied Chemistry (IUPAC) for more than a decade. He was president of the 52
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IUPAC Division of Organic Chemistry, 1991-93. Leonard has lectured in many countries around the world and received numerous awards and honors. His knowledge of and experience with DNA and related substances has been in demand for lectures at biotechnology firms. He was the Tanabe Research Lecturer in 1993 at Scripps Research Institute in La Jolla, Calif., and he received the first University of Oregon Outstanding Achievement Award in Chemistry this year. Leonard received a B.S. degree from Lehigh University in 1937 and a Ph.D degree from Columbia University in 1942. He was a Rhodes Scholar at Oxford University, where he received a B.Sc. (1940) and a D.Sc. (1983). Leonard has been a member of several editorial boards of chemistry journals and a member of government chemistry panels and committees, and he has held various ACS positions. He has more than 430 scientific publications to his credit. KURT M. MISLOW, Hugh Stott Taylor Professor of Chemistry Emeritus at Princeton University, has been called the premier stereochemical theorist and experimentalist today. His work has helped define modern stereochemistry and covers three areas of focus. Mislow pioneered non- and counterintuitive stereochemical theory. He was the first to conceive of and synthesize a molecule that was chiral in all static conformations but was fluxionally racemic. He was among the first to identify the inadequacies of the standard bonding graph in describing stereochemical problems. This allowed him to develop an analysis of stereoisomers based on the complete molecular graph, as well an analysis based solely on the symmetry of the molecular model in the absence of bonds altogether. Mislow's research has also uncovered several novel types of stereoisomerism in substituted biphenyl and triphenyl-X (propeller) systems. The biphenyl work characterized astropisomerism about sj^-sp2 bonds, and through these types of systems, he was able to elucidate the steric effect of deuterium. The triphenyl-X systems were the first examples of residual diastereomerism caused by correlated rotation. This discovery contradicted the idea that conformers could be distinctly described by specification of torsion an-
gles. Conformers of this type require an angle plus a phase relation of all correlated rotors. Born in Berlin, Mislow received a B.S. degree in chemistry (with honors, Phi Beta Kappa) from Tulane University in 1944. In 1947, he received a Ph.D. degree in chemistry from California Institute of Technology, where his research adviser was Linus Pauling. In 1990, he received a Distinguished Alumni Award from Caltech. Mislow joined New York University in 1947 as an instructor in the chemistry department and was promoted to full professor in 1960. He joined Princeton as Hugh Stott Taylor Professor of Chemistry in 1964 and was named professor emeritus in 1988. He was chairman of the Princeton chemistry department from 1968 to 1974. He has published one book, "Introduction to Stereochemistry," and more than 320 research papers. Mislow was a John Simon Guggenheim fellow twice (1956,1974) and was an Alfred P. Sloan Foundation fellow (1959-63). He has been awarded the Solvay Medal (1972) from the Free University of Brussels and the Prelog Medal (1986) from the Swiss Federal Institute of Technology. Mislow received the American Chemical Society's James Flack Norris Award in Physical Organic Chemistry in 1975 and the William H. Nichols Medal from the ACS New York Section in 1987. In 1972, he was elected a member of the National Academy of Sciences, and in 1974, he became a fellow of the American Academy of Arts & Sciences. In the six years she has been a member of the Yale University chemistry faculty, ALANNA SCHEPARTZ has established herself as a leader in the field of bioorganic chemistry with research probing several important questions at the interface of chemistry and biology. Using the tools of synthetic and physical organic chemistry in combination with molecular biology, Schepartz is working to define the chemical principles that govern protein folding, RNA recognition, and protein-DNA interactions. One colleague says of Schepartz that she "brings to her discipline a keen intellect, a penchant for organization, and an indomitable work ethic" and that she "provides keen insights at the molecular level, which are the
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Mislow
Schepartz
trademark of chemists, to problems which would normally be attacked by biologists." One area of research in Schepartz's lab has been development of protein cleavage reagents, which have potential use for studying protein-protein interactions and protein folding and for mapping drug-binding sites on proteins. Recently, the group developed an agent that mediates protein hydrolysis, an important step toward establishing protein cleavage as a general method for identification of drug-binding sites on protein surfaces. Another focus of research in Schepartz's lab has been the design and synthesis of "tethered oligonucleotide probes" (TOPs) for molecular recognition of large, structured RNA molecules. Although formally single-stranded, RNA molecules form base-pairs intramolecularly, and the resultant "stem loops" fold to generate molecules with far greater structural complexity than the familiar duplex DNA. TOPs consist of two short oligonucleotides, which complement two noncontiguous regions in a target RNA and provide sequence specificity, linked by a synthetic tether that provides structural specificity. The constructs also have potential as novel antisense inhibitors of gene expression. Schepartz and coworkers have also prepared a series of synthetic peptides that are providing insights into the mechanism of site selection of a class of DNA-binding proteins known as bZIP proteins. These proteins are characterized by a helical "zipper" domain that mediates protein dimerization and an adjacent basic domain that contacts DNA. The two domains are separated by six amino acid residues. The active dimeric DNA-binding entity is generated when the zipper domains of the two
Snider
protein monomers assemble into a parallel coiled coil. The Yale chemists have constructed molecules in which the coiled coil of a bZIP protein is replaced by a series of stereochemically defined metal-ion complexes that systematically alter the relative orientation of the basic domain peptides. The results of these experiments demonstrate that both the affinity and the specificity of these peptides may be modulated by seemingly small changes in orientation. They also suggest that the detailed architecture of the basic-linker domain plays a dominant role in bZIP-DNA interactions. Schepartz received a B.S. degree in chemistry in 1982 from the State University of New York, Albany, and a Ph.D. degree in chemistry in 1987 from Columbia University. After a year of postdoctoral study at California Institute of Technology, Schepartz joined the Yale faculty as an assistant professor of chemistry. She became the Milton Harris-,29 Ph.D. Associate Professor of Chemistry in 1994. Over the past 20 years, BARRY B. SNIDER's laboratory has made notable contributions in the field of organic synthesis. His research has focused on initiating carbon-carbon bond formation and constructing carbon skeletons by attaching a functionalized carbon atom or chain to a double bond using ene and other Lewis acid-induced reactions, intramolecular [2 + 2] cycloadditions of ketenes with alkenes, and manganese(III)-based oxidative free-radical cyclizations. His initial work investigated ene chemistry, studying ways to make this reaction into a generally useful synthetic method through the use of Lewis acid catalysis. With appropriate catalysts, the ene reaction is general, and
proceeds with high regio- and stereospecificity. During the course of his work, he developed the use of alkylaluminum halides as Lewis acids that are Brônsted bases. Subsequent work on intramolecular cycloadditions of ketenes with alkenes led to the development of short and efficient syntheses of β-pinene, chrysanthenone, jasmonic acid, the estrone skele ton, and the bergamotenes. Snider has also developed manganese(III)-based oxidative free-radical cyclizations that can be used to form one, two, or three rings, yielding highly functionalized products from simple starting materials. The key feature of this reaction is that a radical is generated simply by oxidation of a 1,3-dicarbonyl compound and the cyclized radical is oxidized to an alkene with copper(II). This reaction has been used for syntheses of the biologically ac tive natural products podocarpic acid, velloziolone, avenaciolide, aloesaponol III, and okicenone. Snider's contributions in total syn thesis include the development of short and efficient routes to ptilocaulin; ramulosin; reiswigins A and B; crambines A, B, CI, and C2; chondrillin; plakorin; pyridoxatin; compactin; mevinolin; pseudomonic acid; and the pentacyclic core of ptilomycalin A. This work is characterized by attention to the effi ciency of synthetic design and to devel opment of new methodology to solve synthetic problems more efficiently. Snider received a B.S. degree from the University of Michigan in 1970 and a Ph.D. degree from Harvard Universi ty in 1973. His postdoctoral work was at Columbia University, 1973-75. He was an assistant professor at Princeton from 1975 to 1981. He then moved to Brandeis University, where he has re mained since joining the faculty as an associate professor. Snider became a full professor in 1985 and chairman of the chemistry department in 1992. The award winner has authored or coauthored more than 160 scientific publications. He has received a number of awards, including fellowships from the National Science Foundation and the National Institutes of Health, a Sloan Foundation Fellowship, and a Camille & Henry Dreyfus Foundation Teacher-Scholar Award. Snider is a member of the NIH Medicinal Chemis try Study Section, the American Chem ical Society, and the Royal Society of Chemistry. NOVEMBER 14,1994 C&EN
53
AWARDS Throughout his research career, CRAIG A. TOWNSEND has worked at the interface of chemistry and biology, at tacking difficult problems of natural product biosynthesis and uncovering solutions through imaginative yet rigorous experiments. "It is as if he has higher standards than everyone else/7 a colleague writes, "yet elegant ly achieves those standards in each of his published reports." Townsend, professor of chemistry at Johns Hopkins University, approaches natural product biosynthesis on chemi cal, enzymatic, and genetic levels simul taneously. Blending techniques from dif ferent disciplines has allowed him and his coworkers to develop penetrating in sights that might not have been so clear if they had attacked the problems from only one perspective. "He combines and handles total synthesis, stereolabeling, and microbiology in an elegant manner that gets to the heart of the mechanistic and kinetic problems in a way which others in the field can only envy," ac cording to another colleague. While a graduate student, Townsend helped pioneer the use of stable isotope nuclear magnetic resonance spectrosco py in biosynthetic studies, applied most notably to the biosynthesis of vitamin B12. He carried out an elegant and often quoted synthesis of chiral acetic acid during a postdoctoral fellowship. With his own research group at Johns Hopkins, Townsend has focused on un derstanding the biosynthetic pathways leading to β-lactam antibiotics and the environmental carcinogen aflatoxin. He and his coworkers also investigated the enzymology of the biosynthetic transfor mations they have identified. Most re cently, Townsend employed a similarly broad repertory of methods to probe the interaction of DNA with calicheamicin, a diynene antitumor antibiotic. Townsend received a B.A. degree with honors in chemistry from Williams College in 1969 and a Ph.D. degree in organic chemistry from Yale University in 1974. He spent two years as an inter national exchange postdoctoral fellow of the Swiss National Science Foundation at the Swiss Federal Institute of Technol ogy in Zurich before joining the Johns Hopkins chemistry faculty in 1976. He also holds joint appointments in the de partments of biology and biophysics. He served as chemistry department chair man from 1990 until July 1994. He has published more than 80 scien 54
NOVEMBER 14,1994 C&EN
tific papers, delivered doz ens of invited lectures, and was a co-organizer and cofounder of the Bioorganic Chemistry Gordon Re search Conference. He also received a Camille & Henry Dreyfus Foundation Teach er-Scholar Award (1983-88), the Stuart Pharmaceuticals Award in Chemistry (1986), and Maryland Chemist of the Year award (1992). Townsend Waymouth In the time that ROBERT WAYMOUTH has been at Stanford Uni This discovery is important because it versity, he has established himself as a provides a creative solution to the long leader in a rapidly developing field of standing problem of introducing func organometallic-polymer chemistry. His tionality into polyolefins. He has demon work is distinguished by creativity in strated that these catalysts will also copodeveloping new polymerization reac lymerize functionalized monomers with tions as well as unusually deep and ethylene and propylene to produce a new thoughtful investigations into the mech family of functionalized polyethylenes and polypropylenes. This new synthetic anisms by which polymers form. According to a colleague, "Way- development presents excellent opportu mouth exemplifies the kind of science nity for the synthesis of new polymers of that will be critical in the future. He is si well-defined structure and functionality. multaneously an inorganic chemist, an More recently, he has devised a new organometallic chemist, an organic chem strategy for the synthesis of stereoblock ist, and a polymer chemist. He is interest α-olefin copolymers consisting of alter ed in the product of research, not the pa nating atactic and isotactic block stereorochial following of a single subfield." sequences. This strategy hinged on the He has pioneered the application of design and synthesis of a catalyst that well-defined organometallic catalysts for changes its structure on the timescale of stereoselective and enantioselective poly the synthesis of a single polymer chain. merization reactions. Waymouth was the As the catalyst changes its structure first to carry out detailed studies on the from isospecific to aspecific and back again, a stereoblock polymer results. stereochemistry of cyclopolymerization. He has also made exciting advances These studies culminated in the de velopment of a new strategy for the en in the synthesis of polysilanes—poly antioselective synthesis of chiral poly mers made up of catenated silicon mers. His development of enantiose atoms. He developed a catalytic syn lective cyclopolymerization represents thesis of stereoregular polysilanes and a major conceptual advance in polymer recently discovered a remarkably selec synthesis because it creates polymer ar tive procedure for introducing func chitectures that are chiral by virtue of tional groups into the polysilane back their configurational main-chain stereo bone. These developments provide ac chemistry. Waymouth's contributions cess to a new class of electroactive encompass not only the development of silicon polymers of defined structure new synthetic methods for enantioselec and functionality. tive polymer synthesis, but also the devel Waymouth received a B.A. degree in opment of methods for describing and chemistry and a B.S. degree in mathe analyzing the microstructure of these matics from Washington & Lee Univer structurally complex macromolecules. sity, Lexington, Va., in 1982. In 1987, he Waymouth has also devised a new received a Ph.D. degree in chemistry procedure for polymerizing functional- from California Institute of Technology ized olefins with homogeneous Ziegler- under R. H. Grubbs. He was a postdoctor Natta catalysts. Olefins containing suit al fellow with Piero Pino at the Swiss Fed ably protected functional groups were eral Institute of Technology, Zurich, in polymerized with a new class of alumi 1987. He joined the faculty at Stanford in num-free Ziegler-Natta catalysts to pre 1988 as an assistant professor, rising to • pare highly functionalized polyolefins. associate professor earlier this year.
