Natural products from plants, bacteria, and fungi play an important role in society. Over the last 35 years, natural products and their derivatives have inspired over 60% of all FDA approved small-molecule drugs, and are among the top prescribed therapeutics.1-2 Fleming’s discovery of the fungal antibiotic penicillin started the “Golden...
This thesis describes an investigation of the natural products chemistry of two fungal species of the genus Tolypocladium. Natural products are small organic molecules that are considered non-essential for cell growth and reproduction, and thus part of secondary metabolism. Chemical profiling of these secondary metabolites using a combination of high-performance...
Enantioenriched sp³-hybridized carbenoid reagents CR1R2MX (X = nucleofuge, M = electrofuge) of different types were investigated for the synthesis of polysubstituted alkyl chains by iterative stereospecific reagent-controlled homologation (StReCH) and for the stereospecific connective synthesis of alkenes by eliminative cross-coupling.
In the first part, putative enantioenriched α-chloroalkyllithiums (CHRLiCl) were employed...
Molecular chirality plays a critical role in chemistry, biology, and medicine. To study and better understand conformational chirality, it is necessary to obtain structurally interesting molecules that exhibit this form of chirality. Our lab utilizes total synthesis and methodological development to obtain conformationally chiral natural products of interest. We believe...
Hydrogen peroxide quantification is of broad interest due to the common use of hydrogen peroxide as an oxidizing agent in industrial processing and laboratory research. Hydrogen peroxide assays are also of general importance for biological studies aimed at understanding the role of in situ generated reactive oxygen species. In the...
Substituted phenols are important substructures for pharmaceuticals, agrochemicals, natural products and biological probe molecules. The properties of phenolic molecules are substantially influenced by the substitution patterns of the phenolic ring. The chemical synthesis of phenols with various substitution patterns is an enduring challenge and multiple strategies have emerged. However, some...
Traditional approaches for the direct preparation of alkenes are unable to fully control either the stereochemical configuration of the carbon-carbon double bond or else the regiochemistry of the substituents surrounding it. The recently introduced concept of carbenoid eliminative cross-coupling (CEXC) offers a remedy to these deficiencies by providing for a...
Dearomatization reactions exist broadly in biosynthesis and chemical synthesis. The highly functionalized atoms of arenes can be masked by it aromaticity, and upon dearomatization, those reactive atoms can be readily applied to bond formation and further manipulation. The total synthesis of (–)-cephalotaxine and (–)- homoharringtonine is described via an oxidative...
Mandelalide A has attracted considerable interest from the synthetic community due to its intriguing structure and important cytotoxic activity. Madeirolide A, a structurally related macrolide, shows promising antifungal activity but no appreciable anticancer activity. This dissertation describes synthetic studies toward mandelalide A, madeirolide A and their hybrid structures.
Part I...
Marine natural products possess an abundance of diverse chemical scaffolds with unique biological activities. By targeting unusual or unique microbial environments within varying marine ecologies we can continue to discover novel chemistry with potentially new molecular targets. The research presented here is focused on exploring unusual chemical ecologies and the...