The high reactivity and electron-withdrawing ability of the nitro group makes it a powerful tool in synthesizing a diverse range of bioactive natural products. The potential of the nitro group was employed via two main methodologies: iron (III)-mediated oxidative dearomatization and oxime carbonate butyrolactone formation to reach three important heterocyclic scaffolds; spiro, tropone and γ-butyrolactone. Nitro precursors were enantioselective synthesized by key nitro-aldol (Henry) and nitro-Michael reactions. A library of polysubstituted butyrolactone oxime carbonates were formed under mild DMAP and Boc2O conditions from readily available δ-nitroalcohols in good to high yields with broad functional group tolerability. Six lignan γ-butyrolactone natural products were directly accessed from oxime carbonate substrates including (-)-hinokinin, a promising future Chagas therapeutic with strong antitrypanosomal activity, and (-)-bicubebin B, a unique dimer featuring six contiguous stereocenters. Significant progress was made towards the total synthesis of (-)-curcusone C, a cytotoxic diterpenoid shown to suppresses cancer cell migration, and cancer cell proliferation. An SET oxidative dearomatization cyclization reaction in the presence of K3[Fe(CN)6] oxidant and KOH base was called upon to form the tricylic 5-7-6 carbon skeleton in a single cascade step. This convergent synthesis relied upon Suzuki coupling of nitro functionalized alkyl species and halogenation of hydroxy indanone. To invert the absolute configuration of spiro carbon quaternary centers, oxidative dearomatization of phenolic precursors outfitted with leaving groups underwent Grignard conditions. This body of work emphasizes that the reactivity of the nitro groups can be utilized throughout an entire synthetic pathway, providing access to a diverse range of bioactive natural products.
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Doctor of Philosophy (Ph.D.)
College of Sciences
Length of Campus-only Access
Doctoral Dissertation (Open Access)
Bobek, Katelyn, "Harnessing the Power of the Nitro Group in Natural Product Synthesis" (2022). Electronic Theses and Dissertations, 2020-. 1363.