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2003
McCoy Award Recipient
Philip L. Fuchs
Professor Department of
Chemistry
"Chemistry, Computers, and Cancer"
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.
Title of Lecture
"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.
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