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.