Cascade cyclizations & the schweinfurthins

Publication Year:
2011
Usage 395
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Repository URL:
http://ir.uiowa.edu/etd/2780; https://ir.uiowa.edu/cgi/viewcontent.cgi?article=2679&context=etd
Author(s):
Topczewski, Joseph John
Publisher(s):
University of Iowa
Tags:
Antiproliferative Agent; Anti-Proliferative Agent; Cascade Cyclization; Natural Product; Schweinfurthin; Total Synthesis; Chemistry
thesis / dissertation description
Cancer is a serious family of disease that continues to cripple and claim those afflicted. For the last several decades, America has invested in a national program to alleviate cancer and cancer related suffering, ultimately seeking a cure. As part of this goal, the National Cancer Institute (NCI) has spent significant effort scouring the globe with the hope of finding naturally occurring compounds that can successfully combat cancer. Presently, this effort has uncovered many natural products with chemotherapeutic potential and many of the lead agents used in the fight against cancer are either natural products themselves or are compounds inspired by a natural product.This work describes one family of natural products uncovered by the NCI that is being explored for chemotherapeutic applications, namely the schweinfurthins. The schweinfurthins were isolated by the NCI; however the natural source, Macaranga schweinfurthii, did not provide these compounds in ample quantity to permit further study. The paucity of natural material indicated that a chemical synthesis of these compounds would be the most reliable method to provide meaningful amounts of schweinfurthins. The present work describes the chemical synthesis of four of the most potent schweinfurthins, describes the synthesis of numerous structural analogues, and details advances to the field of cascade cyclizations which makes their synthesis possible.