February 27, 2012 - IMM@BUCT

University. Aubé is the first
person in his family to earn a
college degree.
Today, Aubé is a professor
of medicinal chemistry
at the University of Kansas.
His research group is best
known for its discovery of
the intramolecular Schmidt
reaction, in which an alkyl
azide and a ketone react to
form a lactam.
In the classic Schmidt reaction,
a six-membered ring
such as cyclohexanone can
be converted into a sevenmembered
ring. “If you use
Aubé
our variation, you can attach the azide to
the cyclohexanone so your product now
has two rings associated with it, and it just
so happens that those kinds of two-ring
structures with a nitrogen at one of the
ring fusions are present in a lot of different
natural products,” Aubé says.
The intramolecular Schmidt reaction
“allows one to consider synthesis of
otherwise untouchable targets, such as
the prototypical twisted amide 2-quinuclidone,”
says Brian M. Stoltz, professor
of chemistry at California Institute of
Technology. “In my own research, we were
able to construct this long-standing target
only through the use of the intramolecular
Schmidt reaction.”
Using the intramolecular Schmidt reaction,
Aubé says, members of his group have
made a number of alkaloids isolated from
frog toxins. They’ve also made alkaloids
from traditional Chinese medicine, such
as the molecule stenine. Aubé’s group was
able to reduce the number of steps in its
previous synthesis of stenine by more than
half.
“What is most impressive about Jeff is
that the field learns something it did not
know every time he discloses one of his
publications,” says Dale L. Boger, professor
of chemistry at Scripps Research Institute.
Aubé continues to develop new methodologies
and uses those reactions to build
chemical libraries. He screens those libraries
and follows up on interesting biological
leads for potential drugs.
“Jeffrey Aubé has consistently built
a record of excellence in the development
of synthetic methods and their
application to the syntheses of natural
products, physical organic chemistry, and
bioorganic chemistry,” says Barbara N.
Timmermann, professor and chair of the
UNIVERSITY OF KANSAS
Described by colleagues as
fearless for his willingness
to tackle intractable biochemical
problems, Squire
J. Booker is being honored
with an Arthur C. Cope
Scholar Award for his efforts
to understand enzymes that catalyze
“kinetically challenged” reactions.
The enzymes that Booker studies typically
use S-adenosyl-l-methionine (SAM),
iron-sulfur clusters, or both to generate
cellular oxidants under anaerobic conditions.
The pathways arose during primordial
times, when cells had to work without
oxygen, Booker says. His
studies require special experimental
care, because
much of the work must be
done anaerobically—including
growing crystals for X-
ray crystallography.
Booker’s work is “always
highly original and rigorously
designed and executed,” one
colleague says. “I expect him
to become one of the most
highly regarded authorities
on biological mechanisms.”
An associate professor
of chemistry and biochemistry
and molecular biology
department of medicinal
chemistry at the University
of Kansas. “All of these
efforts are characterized
by an unusual degree of
creativity, attention to
detail, rigor, and above
all, individuality.” —LINDA
WANG
Booker
at Pennsylvania State University, Booker
started his research program by studying
lipoic acid synthase, an enzyme that had
stymied other researchers, says his Penn
State colleague J. Martin Bollinger Jr. The
enzyme produces lipoic acid, a cofactor
used by several other enzymes, by inserting
sulfur atoms into octanoic acid through a
mechanism involving a SAM-derived radical.
Booker and coworkers found that the
sulfur atoms are sourced from a sacrificed
iron-sulfur cluster.
More recently, Booker studied SAM-dependent
methylation of RNA carbon atoms
that are normally considered inert to such
reactions. Both of the enzymes he studied
methylate RNA in bacterial ribosomes; one
group promotes normal ribosome func-
tion and the other promotes antibiotic
resistance. Booker and colleagues found
that the methylation mechanism involves
a ping-pong reaction in which the enzymes
first transfer a methyl group from SAM to a
cysteine residue, then a second SAM generates
a 5'-deoxyadenosyl radical that relocates
the methyl from the cysteine to the
adenosine base through a radical-addition
mechanism.
Booker has also studied a bacterial
enzyme that uses iron-sulfur clusters to
make quinolinic acid as part of the bacterial
biosynthetic pathway for nicotinamide
adenine dinucleotide (NAD + ), a common
cellular cofactor. One of his findings is that
the amount of oxygen available regulates
one of the enzymes in the NAD + synthetic
pathway through a dithiol/disulfide redox
switch: In the disulfide form, the enzyme
activity is 10 times as much as when it’s in
the dithiol form. That makes sense, Booker
says, because bacteria require higher concentrations
of NAD + to grow in aerobic
conditions. His group continues to tease
out the details of the switch
and the enzyme’s catalytic
chemistry.
Booker, 46, earned a B.A.
degree with a concentration
in chemistry from
Austin College in 1987 and
a Ph.D. in chemistry from
Massachusetts Institute of
Technology in 1994.
Aside from Booker’s
laboratory successes, he is
lauded for his mentorship
and ability to turn students
into outstanding scientists.
Booker’s combination of
critical analysis and interpersonal
skills also puts him in demand for
service to Penn State as well as the broader
chemistry community. Booker rarely refuses
a request for his time, Bollinger says, “he
is as unselfish and community-minded as he
is scientifically gifted.” —JYLLIAN KEMSLEY
PENN STATE U DEPARTMENT OF CHEMISTRY
Timothy F. Jamison’s penchant for making
and mixing things can be traced back
to his part-time job in high school at
Swensen’s, an ice cream parlor where he
made 100 or so gallons of the treat on a
typical afternoon.
At age 44, Jamison is still enamored
with making and mixing things, but of a
different kind. Inspirational high school
teachers and a formative undergraduate research
experience convinced him to trade
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