people
|Faculty
|Kay Brummond
 |
Kay Brummond Department of Chemistry |
The Brummond group is involved in: 1) the development of new synthetic methods to facilitate the construction of complex molecules in a stereo- and regioselective manner; 2) the application of these new methods to the synthesis of biologically important compounds; and 3) the design of novel methods for the attachment of small molecules to the solid support for the application to library preparation.
The Pauson-Khand (P-K) reaction has received a remarkable amount of attention due to its synthetic potential and the rapid increase in molecular complexity during the conversion of starting material to product. We have successfully expanded the scope of this reaction by using alkynyl allenes that afford products with substructures that are not readily accessible using existing synthetic methods, a-alkylidene and 4-alkylidene cyclopentenones. This method has been successfully applied to the synthesis of hydroxymethylacylfulvene (HMAF), an anticancer compound soon to enter Phase III clinical trials. Moreover, a silicon-tethered version of this reaction is currently being applied to the synthesis of 15-deoxy-D12,14 PGJ2, a natural ligand for the PPAR, a receptor that has been linked to Type II diabetes and obesity.
Natural products have provided molecular biologists with a vast source of molecules for the study of protein function. Thus, the creation of libraries of structurally diverse molecules utilizing a natural product like scaffold becomes attractive. A natural product that contains a particularly well-suited structure to serve as a scaffold for the preparation of a library of compounds is FR901483. This compound has been shown to exhibit potent immunosuppressive properties via a mechanism that is different from that of cyclosporin A or tacrolimus (FK 506). The substructure of FR901483 is not present in another natural product characterized to date, and it possesses rigidity that should aid in protein binding and specificity. Thus, a library of functionally diverse compounds possessing this tricyclic core would represent a unique collection of compounds not currently available for biological screening. We have demonstrated on a model system that this compound may be accessible using a tandem cationic aza-Cope rearrangement/Mannich cyclization strategy, thus are currently working on the total synthesis of FR901483 and the preparation of a library of analogs.
Awards
Johnson & Johnson Focused Giving Award; The Chancellor's Distinguished Research Award
Selected Publications
"Heterocyclic alpha-Alkylidene Cyclopentenones Obtained via a Pauson-Khand Reaction of Amino Acid Derived Allenynes. A Scope and Limitation Study Directed Towards the Preparation of a Tricyclic Pyrrole Library," Kay M. Brummond, Dennis P. Curran, Branko Mitasev, Stefan Fischer, J. Org. Chem., 2005, 70, 1745
"A Formal Total Synthesis of FR901483 Using a Tandem Cationic aza-Cope Rearrangement/Mannich Cyclization Reaction.," K. M. Brummond and Sang-phyo Hong, J. Org. Chem., 2005, 70, 907
"Rhodium(I)-Catalyzed Alder Enyne Reactions in Modern Rhodium-Catalyzed Transformations.," K. M. Brummond and J. M. McCabe, P. Andrew Evans, ed. Wiley VCH, 2005,
"Consecutive Rh(I)-Catalyzed Alder-ene/Diels-Alder/Diels-Alder Reaction Sequence Affording Rapid Entry to Polycyclic Compounds," K.M. Brummond and Lingfeng You, Invited Tetrahedron Symposia-in-Press Applications in Catalysis in Industry and Academia., 2005, 61, 6180
"Allenes and Transition Metals: A Diverging Approach to Heterocycles," K.M. Brummond, B. Mitasev, Organic Lett., 2004, 6, 2245
"A Rhodium(I) Catalyzed Ene-Allene Carbocyclization Strategy for the Formation of Azepines and Oxepines," K. M. Brummond, H. Chen, B. Mitasev, A. D. Casarez, Organic Lett., 2004, 6, 2161
"The First Total Synthesis of 15-Deoxy-D12,14-Prostaglandin J-2 and the Unambiguous Assignment of the C14 Stereochemistry," K. M. Brummond; H. Chen.; P. Sill., Organic Lett., 2004, 6, 149
"Allenes in Natural Product Synthesis in Modern Allene Chemistry.," K. M. Brummond and H. Chen,, N. Krause, ed., Wiley VCH, 2004, 2, 1041-1090.
"Unique Strategy for the Assembly of the Carbon Skeleton of Guanacastepene A Using an Allenic Pauson-Khand-Type Reaction," K.M. Brummond*; D. Gao, Organic Lett., 2003, 5, 3491
"A Rhodium(I)-Catalyzed Allenic Alder-ene Reaction for the Rapid and Stereoselective Assembly of Cross-Conjugated Trienes," K.M. Brummond; H. Chen; P. Sill, L. You, J. Am. Chem. Soc., 2002, 124, 15186
