Issue Date: February 23, 2009
Elias J. Corey Award for Outstanding Original Contribution in Organic Synthesis by a Young Investigator
Sponsored by the Pfizer Endowment Fund
The laboratory of Brian M. Stoltz, 38, the Ethel Wilson Bowles & Robert Bowles Professor of Chemistry at California Institute of Technology, has been described as one of the major sources of new strategies for constructing complex molecules. His group has completed total syntheses of a number of biologically and structurally interesting molecules.
The first major targets were members of the dragmacidin family of marine alkaloids, a class of natural products rich with biological activity ranging from phosphatase inhibition to anti-HIV activity. Critical to his success in this area was implementation of oxidative cyclization chemistry developed in his laboratory. These syntheses highlight the interplay between total synthesis efforts and methodology development.
In addition to the dragmacidins, his group accomplished the first total synthesis of the glycosylated tetrahydroisoquinoline antitumor antibiotic lemonomycin. And they completed the first synthesis of the original “anti-Bredt” amide, 2-quinuclidone. This molecule was the subject of numerous attempted syntheses during the past 70 years; however, Stoltz’s unambiguous synthetic design involving a keto-azide rearrangement produced the molecule for the first time in an isolable fashion as its HBF4 adduct.
These total synthesis studies, coupled with a number of other synthetic problems under investigation in the Stoltz laboratory, have led to the development of numerous new synthetic methods. His studies have been spread over three major conceptual areas: the advancement of palladium-catalyzed oxidation reactions that do not involve heteroatom transfer, the development of asymmetric alkylation and protonation technologies for the synthesis of quaternary and tertiary stereocenters, and the invention of tandem reaction processes for synthesis.
In the first area, his group pioneered the development of palladium-catalyzed enantioselective oxidase-type reactions including the development of an oxidative kinetic resolution, meso diol desymmetrization, and oxidative heterocyclization chemistry that utilizes O2 as the stoichiometric oxidant. This methodology was critical in the completion of dragmacidin F.
In the second area, his group has developed a highly practical enantioselective method for alklylating enolates generated in situ. This methodology allowed the rapid, protecting-group-free total synthesis of the norditerpenoid (–)-dichroanone. Additionally, his group has developed a slightly different procedure that allows the catalytic enantioselective synthesis of tertiary stereocenters by asymmetric protonation of the enolate. These methods will facilitate the catalytic enantioselective preparation of highly useful chiral building blocks for use in natural products and pharmaceutical synthesis.
The final realm of methodological development in the Stoltz laboratory involves the development of novel tandem reactions in catalysis and synthesis. His group has developed four independent tandem processes of note: the Bamford-Stevens Claisen rearrangement process, the Wolff-Cope rearrangement, the catalytic enantioselective double alkylation reaction, and the acyl-alkylation of arynes. They recently utilized the acyl-alkylation reaction in conjunction with an oxidative kinetic resolution to produce the isopavine alkaloid (–)-amurensinine. These reactions and others like them will be highly useful for the rapid preparation of complex molecules.
Stoltz has also been described as an outstanding teacher and mentor. He received a Ph.D. in organic chemistry from Yale University in 1997, was a National Institutes of Health Postdoctoral Fellow at Harvard University from 1998 to 2000, and then moved to Caltech, where he has been since. He is the recipient of numerous awards and honors, including the ACS Arthur C. Cope Scholar Award (2005), the Camille & Henry Dreyfus Teacher-Scholar Award (2005), and the Presidential Early Career Award for Scientists & Engineers (2004).
Stoltz will present the award address before the Division of Organic Chemistry.
- Chemical & Engineering News
- ISSN 0009-2347
- Copyright © American Chemical Society