In this project funded by the Chemical Synthesis program of the Chemistry Division, Professor Brian C. Goess of the Department of Chemistry at Furman University will develop syntheses of new members of the sesquiterpene furanosteroid family of natural products. These molecules, which include wortmannin, have attracted significant attention for their ability to inhibit the phosphatidylinositol-3-kinases (PI3K), enzymes known to play a critical role in cell growth and differentiation. Syntheses of six new members of this family of natural products, none of which have been previously synthesized, will be developed. Additionally, modifications to the synthesis routes will generate analogs suitable for use in assays to determine the biological activities of these new natural products.
These new natural products are isolated in only minute quantities from their natural sources. Given their important biological activities and their potential as chemotherapeutics, chemical synthesis of each of these molecules is necessary. This work will also enable more efficient methods for the preparation of this entire family of molecules, including those that exist but have not yet been isolated from natural sources. This project could have significant impacts on pharmaceutical industries and general biological studies. This project will also serve as the training ground for undergraduate chemists, many of which will attend graduate schools in chemistry, where the skills they develop on this project will be extensively utilized.