Our group is interested in the exploring the potential of polyketide natural products as chemotherapeutic agents particularly directed against cancer. Towards this end our group's expertise includes synthetic chemistry, molecular modeling, and molecular biology/biochemistry. In recent years the we have completed the total synthesis of the complex natural products, epothilones A, B, C and D, myriaporones 1, 3 and 4, peloruside A, neopeltolide, tolypothrix polyethers, and gephyronic acid.

Our analogue design strategy is focused towards the determination of the structural and conformational constraints of binding. Our group has demonstrated that the information gained from what we have termed conformation-activity relationships complements classic SAR with the goal of providing a detailed pharmacophore model and assist in the design of future chemotherapeutic agents.  In addition to our successful total syntheses and medicinal chemistry efforts, our group has already contributed significantly to the field of organic synthesis through the development of a number of new synthetic methodologies that solved key problems in our targeted efforts.

Another unique aspect of our analogue design strategy is the exploitation of biosynthetic enzymes called polyketide synthases. We are actively pursuing the isolation and characterization of polyketide synthase gene clusters responsible for the production of biologically active natural products. We have demonstrated the semi-synthetic production of epothilone natural products and analogues through the use of genetically engineered organisms thus alleviating any concerns about the high cost of total synthesis of compounds of this complexity.

Synthetic Methodology and Total Synthesis

Conformation-Activity Relationships

Polyketide Synthases and Biosynthesis