Tripterygium wilfordii (T. wilfordii , TW ), a wildly used herb medicine,was tested for anticancer effect on human myeloid leukemia cells, HL60 in this study. The extract powder of T. wilfordii induced the apoptosis of HL60 cells was demonstrated by morphological change, cell viability, DNA fragmentation and caspase-3 activity. However, normal human peripheral mononuclear cells remained viable under the same treatment. The T. wilfordii induced apoptosis of HL60 cells was associated with the increased Bax gene expression and decreased Bcl-2 gene expression. In addition, the gene expression of c-Myc, and hTERT, TP1, but not TR was downregulated in TW treatedHL60 cells in dose-dependent manner. Telomerase activity in HL60 cell was inhibited by the T. wilfordii . C-Myc protein is reported as a positive regulator of hTERT gene in HL60 cells. Therefore, proto-oncogene c-myc might play an essential role in the regulation of telomerase activity in HL60cells exposed to theT. wilfordii . All the treated cells showed a decrease in telomerase activity after T. wilfordii treatment. Taken togather, these results indicate that theT. Wilfordii-induced apoptosis in HL60 is mediated through mitochondrial pathway in parallel with the decrease expression of hTERT gene.

This thesis discusses the progress made towards a formal total synthesis of triptolide, a naturally occurring diterpenoid triepoxide molecule. Isolated from a Chinese vine, triptolide features some interesting structural characteristics and has demonstrated a broad range of interesting medicinal effects. It has demonstrated remarkable cytotoxicity against a number of cancer cell lines, immunosuppressive activity, and reversible male sterility. This biological activity has made it a target of a number of total syntheses spanning from 1980 to 2010. Gold-catalyzed transformations are an emerging field in synthetic organic chemistry, but their efficacy and potential uses are gaining much recognition among the synthetic organic community. Our research group is extremely interested in the applications of such gold-catalyzed organic transformations in natural product synthesis. Here, we discuss our investigations towards accessing the tetracyclic core of triptolide using a gold-catalyzed cyclization cascade reaction. We explored a number of synthetic routes towards a common linear precursor, and our successes and failures are discussed herein. We also report numerous unsuccessful efforts towards an oxidative gold-catalyzed cyclization cascade to form the tetracyclic core of triptolide. Finally, we investigated the use of a photocatalytic radical cyclization cascade to access the desired core. We report some promising preliminary results, and this study is ongoing in the Barriault group.

This thesis discusses the progress made towards a formal total synthesis of triptolide, a naturally occurring diterpenoid triepoxide molecule. Isolated from a Chinese vine, triptolide features some interesting structural characteristics and has demonstrated a broad range of interesting medicinal effects. It has demonstrated remarkable cytotoxicity against a number of cancer cell lines, immunosuppressive activity, and reversible male sterility. This biological activity has made it a target of a number of total syntheses spanning from 1980 to 2010. Gold-catalyzed transformations are an emerging field in synthetic organic chemistry, but their efficacy and potential uses are gaining much recognition among the synthetic organic community. Our research group is extremely interested in the applications of such gold-catalyzed organic transformations in natural product synthesis. Here, we discuss our investigations towards accessing the tetracyclic core of triptolide using a gold-catalyzed cyclization cascade reaction. We explored a number of synthetic routes towards a common linear precursor, and our successes and failures are discussed herein. We also report numerous unsuccessful efforts towards an oxidative gold-catalyzed cyclization cascade to form the tetracyclic core of triptolide. Finally, we investigated the use of a photocatalytic radical cyclization cascade to access the desired core. We report some promising preliminary results, and this study is ongoing in the Barriault group.