Herbert Newby McCoy Award
2003 McCoy Award Recipient
Philip L. Fuchs
Professor Department of Chemistry
Phil Fuchs, professor of chemistry, has been a member of the Purdue University faculty since 1973. Born in Milwaukee, Wisconsin, he grew up near the town of Nashotah (population 237) on an isthmus of land between Okauchee and Garvin lakes. During his grade school years Fuchs' major summer activity was building a shack with his cousins. The ultimate edifice featured three rooms with a patio, a lake view from the top of a hill, screened windows, waterproof roofs, and a gabled kitchen complete with sink, tiled floor, furniture, and a custom-built icebox.
The majority of Phil's grade school education took place in the four-room, Pine Lake Elementary School in Nashotah. Among his schoolmates was an exceptionally bright girl who constantly vexed Fuchs in matters educational. Her name was Diane. In the course of time, a grudging respect evolved, and Diane was allowed the use of Fuchs' baseball glove. In 1959, eighth grade graduation saw the stage decorated in a scientific theme complete with a Fuchs-built Boron atom complete with tubing orbitals and Styrofoam electrons. Fuchs' secondary education took place at Arrowhead High School in Hartland, Wisconsin. At the end of his sophomore year, he and another chemophile, Richard Pariza, decided to renovate an old out-building at the Pariza farm. At the end of that summer, the renovation yielded a laboratory named Willow Brook Laboratory, or WBL. It included epoxy-top lab benches and a homemade fume hood.
During the next two years, the two neophyte chemists purchased a virtually complete pre-lanthanide selection of the periodic table and performed reactions from the literature of organic and inorganic synthesis. Fuchs then attended the University of Wisconsin at Madison, enrolled in a program that allowed 65 of 130 credits to be chemistry. He rounded out his education with physics, math, history (of chemistry), a glassblowing class, and other required humanities. Throughout this enjoyable period, he performed undergraduate research and took five graduate classes in addition to regularly sharpening his statistical skills around the poker table.
While attending UW, Fuchs continued summer projects at WBL, selling reagents to Aldrich Chemical Company in Milwaukee and eventually advertising its chemicals on the back page of the Journal of the American Chemical Society. After receiving his undergraduate degree at the University of Wisconsin in 1968, Fuchs began graduate studies there with Edwin Vedejs. This was followed by a two-year postdoctoral fellowship at Harvard University with E. J. Corey (Nobel Laureate, 1990). Fuchs' non-chemical accomplishments during this time included being on a winning tournament-bridge team, and once defeating the reigning Harvard summer chess champion.
Fuchs began his career at Purdue in 1973. Since that time, he has graduated an extended family of 55 Ph.D.s. His awards and honors include an Eli Lilly young faculty fellowship (1975), an Alfred P. Sloan fellowship (1977), a Pioneer in Laboratory Robotics award (1986), a Martin teaching award (1991), and being voted by the students as one of Top 10 Teachers in School of Science at Purdue (1991, 1993, 1995, 1996). Fuchs has consulted for Pfizer, and Eli Lilly, served on the editorial board of The Journal of Organic Chemistry, and is currently an executive editor for the Electronic Encyclopedia of Organic Reagents (eEROS), an online dynamic encyclopedia sponsored by John Wiley.
Research
Individuals who seek to synthesize meaningful quantities of chemicals face a universal material supply problem: The longer the synthetic route, the more material will be lost through less-than-quantitative reactions. For example, if one considers a linear sequence where the product of reaction 1 is the starting material for reaction 2, etc., and a total of five reactions are conducted, the overall yield will be Y1xY2xY3xY4xY5. Our study of the synthetic organic literature reveal that the best syntheses average 80 percent yield per operation; this means the hypothetical example would have an overall yield of 33 percent. An added consequence of inefficient syntheses is that the expense of disposing of unwanted by-products may often exceed the cost of producing the desired target material.
A constant theme in Fuchs' research has been directed toward applying emerging technology as an adjuvant to organic synthesis. This included using the Radio Shack TRS-80 computer with four disk drives to initially store the ‘cutting edge' total of 1 megabyte of literature citation data. The original program has long since been transported to our Macintosh network and now tracks over 40,000 literature references as well as the group chemical stockroom/archive. Another chapter in the fight for synthetic efficiency involved the integration of laboratory robotics and computers with Purdue-designed and built intelligent workstations for unattended optimization of organic reactions. Fuchs' 1984 paper on this subject (J. Amer. Chem. Soc. 1984, 106, 7143-7145) predated the combinatorial chemistry revolution by five years. More recently, Fuchs has addressed the theoretical basis for designing organic synthesis.
Synthetic organic chemists are often accused of sharing a common heritage with used car salespersons. Both groups of individuals extol the virtues of their product but ignore or actively obfuscate areas of information that cast less favorable light on their wares. Guidelines that correlate the operational length of a synthesis with the structural intricacy of the target and starting material, can provide focus for the synthetic planner. Such discipline fosters aggressive new chemistry and can engender graceful and efficient access to the target. In conjunction with teaching his graduate synthesis class, Fuchs published a Tetrahedron paper in 2001 on the subject of “increase in intricacy” as a measure of the quality of an organic synthesis. The premise is that intricacy consists of stereocenters prochiral centers and rings, aryl-Z bonds, and heteroatoms. Weighting factors are not required since the intricacy factors are chemically interconvertible. Introduction of these attributes during the synthesis is a ‘value-added' operation, provided that these features are created by the chemistry rather that simply being attached as preformed segments.
The consequences of paying attention to intricacy factors will be discussed throughout the seminar. For example, the first synthesis of the extraordinarily potent anticancer agent cephalostatin 1 began with two molecules of the inexpensive steroid hecogenin acetate, but employed a questionable strategy wherein atoms were initially excised from the molecule to enable further chemistry. Inspired by the intricacy equation, a fundamentally different approach to 1 is discussed where all atoms are retained, and new oxidative processes are invented as needed.
Chemistry, Computers, and Cancer
Abstract of Lecture
The earth's closed ecosystem is continually assaulted by an increasing array of chemical, biological, and population stresses resulting in consequences that demand scientific remediation. All the while, nature presents an abundant cornucopia of substances whose biological and structural information often proves crucial for drug development. Science and medicine are allies in the two-fold battle of deciphering and eradicating diseases that challenge human existence. Evaluation and development of drugs, including anticancer agents, involves a sequence of increasingly demanding scientific hurdles that a potential agent must exceed. Most of these toxic compounds are excluded from the candidate group because they do not strongly discriminate between cancer cells and healthy cells. The small group of compounds remaining continues to be aggressively culled as animal trials and preliminary trials with healthy humans reveal unacceptable properties. New natural and ‘unnatural' products will continue to be subjected to this arduous procedure, but with odds of around 1-3/10,000, it is clear that new approaches are required. The use of computer-based modeling, in conjunction with synthetic efficiency analysis will be discussed in the context of teaming up with nature to attack the cancer problem.
