A Practical, Enantioselective Formal Total Synthesis of Triptonide and Triptolide
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Authors
Flieth, Keveen J.
Issue Date
2019
Type
Dissertation
Language
Keywords
Azo-Surfactants , Enantioselective , Lutein , Male Contraceptive , Triptonide , Wieland-Miescher Ketone (WMK)
Alternative Title
Abstract
A Chinese plant called Tripterygium wilfordii, also known as the thunder god vine, has been used in traditional Chinese medicine for centuries. Like many plants, the thunder god vine produces several unique natural products with the potential of having biological activity. While many natural products have been isolated from this plant, two of the more distinctive ones are the tri-epoxy diterpenoids triptolide and triptonide (SD-1). Over the years, these two compounds have been tested for a large variety of biological activities relevant to many disorders such as cancers, Alzheimer’s disease, and many more. However, one of the more interesting biological functions these compounds have shown is their ability to decrease the number of active sperm cells in male subjects. This special activity is not only interesting from a scientific point of view but also a social point of view. The development of a drug with these properties could lead to a new method of male birth control, which would expand society’s birth control options, relieving some burden from females. The goals of this project are to develop a formal enantioselective synthesis of triptonide (SD-1) in a cheap and efficient manner, test the synthetic product and compare it to the natural source, and synthesize derivatives for potential improved drug activity. Several methods were attempted for the synthesis of SD-1. In each case, 1,3-cyclohexadione was converted to the racemic or (S)-Wieland-Miescher ketone (WMK). In some cases, a model substrate (cyclohexanone) was used to develop different transformations that would later be tested on the desired substrate. Each step was optimized to obtain the best results possible for each reaction. If a reaction yielded no results after several trials, a new method was developed, all beginning with WMK. Upon completion, the synthetic SD-1 would be tested for biological activity and derivatives would be developed for potential improved drug activity.