Baran and Nicolaou Win
Nobel Signature Award
By Jason Socrates
Bardi
Where most prizes awarded to chemists recognize individual
achievement, one prestigious prize, the Nobel Laureate Signature
Award for Graduate Education in Chemistry, recognizes the
achievements of both an outstanding graduate student and his/her
mentor.
The 2003 winners of the Nobel Laureate Signature Award,
who are chosen each year by the American Chemical Society
(ACS), are The Scripps Research Institute's (TSRI) Phil Baran
and K.C. Nicolaou. At next year's annual ACS meeting, they
will both receive awards sponsored by the company Mallinckrodt
Baker, Inc. of cash prizes and plaques inscribed with the
signatures of Nobel laureates.
Baran is a 2002 graduate of the TSRI Chemistry Program,
and Nicolaou is the Aline W. and L.S. Skaggs Professor of
Chemical Biology and Darlene Shiley Chair in Chemistry. When
he graduated last May, Baran was 24, the youngest graduate
ever of TSRI's Chemistry Program.
"Phil Baran was a phenomenal student at TSRI—tenacious,
enthusiastic, brilliant, imaginative, and so much more," says
Nicolaou. "He grew up here both as a young man and as a scientist.
He matured to the point where I think he is now a formidable
synthetic chemist with an exciting career ahead of him."
Baran, for his part, credits his success to Nicolaou's mentoring
during the four years Baran worked under him. And he also
feels he would not be where he is today without Professor
David Schuster of New York University, with whom he worked
as an undergraduate and published six papers.
"I saw Dr. Nicolaou give a lecture [at the Nichols Award
symposium in New York City] in 1996, and I knew from that
moment that I wanted to work for him," says Baran, who came
to TSRI the following year." The training I received was second
to none."
"Phil needed little direction from me," insists Nicolaou.
"He combined beautifully a sharp mind with a pair of golden
hands, accomplishing an incredible volume of work."
That work involved the total synthesis of the molecules
CP-263,114 and CP-255,917. These "CP molecules" are both natural
products of a fungus that was found on a twig of a Texas juniper
tree in the 1990s. These two similar molecules inhibit the
enzymes squalene synthetase and ras farnesyl transferase,
which are implicated in high cholesterol and certain types
of cancer.
Their activity and potential use as scaffolds upon which
to design anti-cancer and cholesterol lowering drugs makes
the CP molecules interesting targets for synthesis, but their
complexity—which Nicolaou calls diabolical—made
the synthesis seem a daunting task. Baran, however, was undaunted
from the beginning and invited the challenge.
"When I first got here in July 1997, the CP molecules 'spoke'
to me," he says. "My heart turned inside out and my mind started
racing, and I just had to go to the laboratory."
And go to the laboratory Baran did. For the next two years,
he spent days, nights, weekends, and holidays in the laboratory,
wholly devoted to completing the total synthesis of the CP
molecules, which he accomplished in April of 1999.
Along the way, he and Nicolaou discovered many new synthetic
tools and methodologies—ways of carrying out a reaction
that can be used not only for synthesizing a particular CP
molecule, but also generalized for many synthetic reactions.
These new reactions and technologies are often one of the
most important parts of a total synthesis project, as they
may enable the drug discovery and development process for
other compounds. Many of these discoveries Baran and Nicolaou
described in some of the more than 30 papers they published
during Baran's years as a graduate student at TSRI.
Most recently, the two wrote a review on the synthesis of
the CP molecules and all the discoveries they made along the
way, and this appeared on the cover of the August 2, 2002
issue of the journal Angewandte Chemie.
Synthetic chemistry, says Baran, is something like mountain
climbing. Except rather than simply reaching a new peak that
nobody has summited before, you are also inventing new harnesses,
ropes, and climbing tools as you go. And you are finding ways
to ascend with fewer steps than anyone has ever done before.
The journey up the CP mountain, adds Baran, was the most
physically and mentally challenging part of his life. And
also the most rewarding.
"[Phil] is full of ideas and has great creative ability,"
says Nobel laureate E.J. Corey of Harvard University, who
was Nicolaou's post graduate advisor and who hired Baran last
year to do a postdoctoral fellowship in his laboratory.
"He's a joy to work with," Corey adds. "K.C. did a superb
job of bringing him along."
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"Phil Baran [above] was a phenomenal
student at TSRI," says renowned chemist K.C. Nicolaou, Baran's
mentor.
Baran knew from the moment he heard
K.C. Nicolaou (above) lecture that he wanted to work for him.
"The training I received was second to none," says Baran.
Links:
• CP
Molecules Review
• Nicolaou
Laboratory
• Nobel
Signature Award
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