Greener Methods Towards the Synthesis of Stachybotrin D, a Potential Anti-HIV Drug

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Florida Southern College
Stachybotrin D is a secondary metabolite from a sponge-derived fungus with potential applications as an anti-HIV drug. Human immunodeficiency virus (HIV) affects 36.9 million people worldwide and is prone to developing drug resistance. While there are currently several approved HIV therapies, the tendency for mutation requires that we constantly find new anti-HIV drugs, especially those with different binding abilities. Stachybotrin D has several structural features that may promote different binding properties than the drugs currently on the market. This is important with the increase of drug resistance to current drugs used in existing therapeutic cocktails for HIV. Since fungi are unsustainable drug sources, this research focuses on the application of sustainable resources and greener techniques towards the chemical synthesis of Stachybotrin D. Retrosynthetic analysis performed on Stachybotrin D revealed the molecule can be synthesized from three segments. This research is focused on the synthesis of one segment composed of a bicyclic ring fused to a furanyl ring as well as its stereochemically specific substituents. To obtain the desired product, the synthesis incorporated a Robinson annulation using 2-methylcyclohexane-1,3-dione and ethyl vinyl ketone followed by protecting the saturated carbonyl, methylation at the α -position on the unsaturated carbonyl carbon, reducing the methylated carbonyl to an alcohol, and removing the protecting group from the carbonyl. However, after examining methods for methylating the alpha position on the unsaturated carbonyl carbon, the synthesis was revised to synthesis isopropyl vinyl ketone and using it in place of ethyl vinyl ketone in the Robinson annulation in order to add the methyl group in a greener way.
Honors thesis Spring 2019
HIV infections, Stachybotrys, Drug resistance