Carlos Barbas: Arthur C. Cope Scholar Awardee

Carlos F. Barbas III, was nominated "for exceptional creativity and pioneering studies in organic chemistry, particularly in the areas of organocatalysis and the application of organic chemistry to chemical biology."

Aldehydic chemistry has been at the core of much of his work. For example, he and his team have made significant advances in the use of unmodified aldehydes as nucleophiles in catalytic asymmetric Michael reactions, according to one colleague. Previously, the direct use of aldehydes as nucleophiles in catalytic asymmetric synthesis had only been accomplished by using enzymes.

The unique ability of organocatalysis to provide a means of controlling the reactivity of aldehydes, as developed first by Barbas, has since been widely employed and now provides the basis for numerous novel aldehyde functionalization reactions, the colleague adds.

Additionally, Barbas has pioneered a wide variety of catalytic asymmetric multicomponent reactions, including "organo-click" reactions, novel Diels-Alder reactions, and tandem aldol-aldol reactions that led to the first one-pot synthesis of carbohydrates. This work stems from his discovery of the proline-catalyzed intermolecular aldol reaction, which was based on his work in aldolase antibodies. More recently, he has designed novel amino acids that are highly effective anti-Mannich catalysts and has presented a design strategy that allows organocatalysis to work effectively with water as solvent. His pioneering studies now enable the synthesis of each Mannich diastereomer in high enantiomeric excess and provide direction for the conversion of organocatalytic reactions into environmentally benign, water-based reactions.

His studies in chemical biology are also notable for their creativity and contributions. Barbas' studies of the installation of novel enzymatic function in proteins led to the creation of aldolase antibodies, the most efficient catalytic antibodies yet described and the only "artificial" enzymes that match the efficiency of their natural counterpart.

Barbas accomplished this, his nomination letter says, through "creative application of chemical logic" in the design of two generations of mechanism-based haptens.

He has gone on to characterize a family of aldolase antibodies from the perspective of their use in synthesis, their immunological formation, and their structure and mechanism.

He has also developed novel prodrugs and catalytic strategies for cancer therapy and invented a new class of therapeutic drugs in his development of chemically programmed antibodies. Three chemically programmed antibodies are now in human trials for cancer and diabetes.

And Barbas has reported comprehensive studies that now allow creation of proteins capable of binding virtually any DNA sequence and regulating any gene.

He has made seminal contributions in catalysis and chemical biology that highlight organic chemistry as a central science. His contributions have decisively enabled advancements in the field of chemical synthesis in general and organocatalysis and chemical biology in particular, the colleague says.

Barbas, 44, received a Ph.D. in organic chemistry at Texas A&M University in 1989. He earned B.S. degrees in chemistry and physics at Eckerd College in 1985.

He currently holds the Janet & W. Keith Kellogg II Chair as professor in the departments of molecular biology and chemistry at Scripps Research Institute, a post he has held since 1999. Prior to that, he held various junior positions at Scripps Research Institute, following postdocs at the Research Institute of Scripps Clinic and Pennsylvania State University from 1989 to 1991.

In 1997, he cofounded Prolifaron, a biotechnology company acquired by Alexion Pharmaceuticals in 2000, and in 2002, he founded CovX, a biotechnology company acquired by Pfizer in 2008.

Among his many honors, Barbas is the recipient of the 2009 Tetrahedron Young Investigator Award.—Patricia Short