Principal Investigator Rick Danheiser
Research interests of the Danheiser Group involves the development of new synthetic methods and strategies, and their application in the total synthesis of natural products and biologically important compounds.
The development of a new synthetic method in our laboratory generally proceeds in three stages. The first stage of each project involves the "pioneer" studies which establish the feasibility of the new reaction and determine optimal reaction conditions. In the second stage of each investigation, the scope, regio- and stereochemical course, and mechanism of the new reaction is explored. The final stage of each study involves the application of the new method in the total synthesis of biologically important natural products.
Currently, the principal objective of this research is the development of new carbon-carbon bond forming reactions, particularly annulation approaches to certain carbocyclic and heterocyclic systems. The Diels-Alder reaction serves as a model for the type of general annulation methods that researchers seek to develop. This classic reaction occupies a position of unique esteem among all ring forming strategies due to its remarkable stereoselectivity, regioselectivity, and broad scope of application. This research is concerned with the development of annulation methods which are inspired by the Diels-Alder reaction, but which apply to the synthesis of other ring systems. Research in Danheiser's group presently focuses on new synthetic approaches to a variety of carbocyclic and heterocyclic systems.
To achieve the synthetic objectives we have exploited a variety of different types of reactions, including:(1) Photochemical processes,(2) "Cascades" of stereospecific orbital symmetry controlled pericyclic reactions,(3) Reactions involving strained rings and reactive functional groups such as ketenes and allenes,(4) New cycloaddition processes based on highly unsaturated conjugated molecules,(5) Reactions involving main group and transition-metal organometallic compounds, and(6) "Environmentally benign" methods for organic synthesis utilizing novel media such as supercritical fluids.
About one-third of current efforts are directed toward the synthesis of biologically important natural products using new methods previously developed in the laboratory. The synthesis of antitumor agents, antifungal antibiotics, hypocholesteremic agents, and neurotoxic alkaloids are currently under investigation. The goal in these projects is to develop highly efficient and practical synthetic routes which are capable of supporting the preparation of sufficient quantities of the target compound for the investigation and/or exploitation of its interesting biological activity. In related studies, group members are also investigating the synthesis of several "unnatural products", including, in particular, polycyclic aromatic systems with unusual electronic properties.