Sessler Lectureship: Professor K. Barry Sharpless, The Scripps Research Institute

Sessler Lectureship: Professor K. Barry Sharpless, The Scripps Research Institute
Date
Wed November 9th 2005, 12:00am
Event Sponsor
Chemistry Department
Location
Carl F. Braun Lecture Hall

About the Seminar: 

"Stitching with Nitrogen" 

Molecules produced by the living systems have always inspired synthetic organic chemists. With the fields of organic and medicinal cheimstry evolving as they did from a desire to explore and learn from the chemistry of life, the practitioners of these disciplines have naturally favored using reactions which are similar to the prototypical biosynthetic pathways. As a consequence, today's favorite targets, both in academic and industrial pharmaceutical chemistry laboratories, are some of the most complex natural substances ever discovered. Lacking her exquisite and complex strategems to steer this essentially thermoneutral chemistry, synthetic organic chemists have learned to rely on such highly reactive agents as organolithiums and enolates. Thus, modern organic synthesis depends heavily on inert atmospheres and dry solvents to support the use of these extremely basic and/or acidic species, requiring that most hteratom functionality in turn be protected and protic solvents are avoided. A heavy price is therefore exacted when the goal is to synthesize the extensive carbon-carbon bond frameworks found in many natural products. 

Fortunately, the universe of possible small molecule drug candidates remains virtually unexplored: the ratio of synthesized to reasonably possible structuers is roughly the same as the mass ofa proton to the mass of the sun. With this kind of structure space available, we propose a synthetic strategy which relies upon heteroatom-carbon bond connections and the use of at least one relatively high-energy, "spring-loaded" component, making the bond-forming processes pre-programmed and exergonic. New molecules of dazzling complexity can arise from very short reaction sequences between spring-loaded blocks which become permanently united together via heteroatoms. We begin with nitrogen, which is second only to carbon in its connectivity potential in organic chemistry. 

 

About the Speaker:

Unlike most academics engaged in basic research, Professor K Barry Sharpless has always been exclusively interested in useful chemistry. Since he regards the oxidation of olefins as the single most versatile, powerful and reliable class of transformations in organic synthesis, Professor Sharpless concentrates on expanding the scope of existing oxidative reactions and discovering new ones.

Professor Sharpless is best known for discovering three "name" reactions, 
general methods for catalytic asymmetric epoxidation, dihydroxylation, and aminohydroxylation. His Nobel Prize citation says, "many scientists have identified Sharpless's epoxidation [discovered in 1980 with Tsutomu Katsuki] as the most important discovery in the field of synthesis during the past few decades."


Descended from one of the original land purchasers in William Penn's New World venture, Professor Sharpless received a Quaker education at the Friends Central School, Haverford, Pennsylvania. In 1963 he graduated from Dartmouth College, where he was introduced, most fortuitously, to the wonders of chemistry and chemical research by T A Spencer. Following graduate research with E E van Tamelen at Stanford University, Professor Sharpless completed postdoctoral studies with J P Collman, also at Stanford, and at Harvard University with Konrad Bloch. While Professor Sharpless was a graduate student, he recognized a role model in D H R Barton; later, and until his death, Sir Derek became Professor Sharpless's valued mentor.


Professor Sharpless set up his own laboratory in 1970 when he became an assistant professor at the Massachuetts Institute of Technology. Except for several years in the 1970s when he was a member of Stanford's chemistry faculty, Professor Sharpless remained at MIT until moving to the Scripps Research Institute (TSRI) in 1990. At TSRI he is W M Keck Professor of Chemistry and a member of the Skaggs Institute for Chemical Biology.


Professor Sharpless continues at TSRI his career-long search for useful new reactivity and general methods for selectively controlling chemical reactions. A recent creation is click chemistry, a set of powerful, virtually 100% reliable, selective reactions for the rapid synthesis of new compounds via heteroatom links. Click chemistry is integral now to all research within the Sharpless Lab, including numerous collaborations with biologists both within TSRI and beyond its walls.