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The production of Ordinary Portland Cement (OPC) and its uses have a complicated environmental impact, which is influenced by infrastructure development and building operations as well as CO2 emissions, which account for 7% of all worldwide CO2 emissions. Due to the increasing population, production is still ongoing. The search for cement and construction materials produced with zero to low CO2 emissions is therefore continuous. Finding recyclable, CO2 gas-free biocomposites with high sulfur content that can rival the mechanical properties of popular building supplies like Portland cement is the primary objective of the research discussed in this dissertation. Chapter one describes the terpenoid as a substitution for olefins in commercially derived polymers. There is an emerging trend in substituting petrochemical derived polymers with sustainable biopolymers to the most commonly used commercial polymers. Terpenoid is an abundant, inexpensive monomer which as characteristic properties and most importantly, polymerizable alkene. Therefore, terpenoids have undergone relatively significant research as starting material for polymer synthesis. Chapter two elaborates the process of inverse vulcanization used to create composites of sulfur-crosslinked terpenoids. It is investigated how High Sulfur Materials (HSMs) with a biopolymeric agent can create a stable sulfur network. Also included are the mechanical, thermal, and mechanical integrity aspects of recycling. And it discusses the investigation of terpenoid cyclization mechanism. The degree to which the amount of terpenoid olefins and the ratio of sulfur to terpenoid affect the thermal and mechanical properties of such terpenoid-sulfur composites is described in the chapter three. Plastic waste pollution of the environment is becoming a significant concern to both human health and the ecosystem. However, even post-consumer plastics that could be easily recycled using straightforward chemical procedures are nonetheless frequently dumped in landfills. Chapter four presents a straightforward, one-stage method for chemically recycling PET to produce composites with mechanical and thermal properties that are competitive with those of widely used structural materials like Portland cement. Chapter five reports the creation and evaluation of mechanical, morphological and thermal properties of a group of composites made of different proportion of guaiacol generated from lignin, fatty acids, and sulfur. To evaluate the impact of unsaturation level on composites, monounsaturated oleic acid and diunsaturated linoleic acid were both employed as the fatty acid components.

This dissertation chronicles the development of a metal-hydride hydrogen atom transfer(MHAT) initiated annulation and its implementation in the synthesis of terpenoid natural products. Chapter 1 introduces the concept of MHAT and relevant transformations developed within this reactivity manifold. The second half of Chapter 1 details our development of a novel MHAT-initiated annulation between α,β- and γ,δ-unsaturated carbonyls to access sterically congested terpenoid motifs. Chapter 2 begins with a brief overview of the biosynthesis and bioactivity of the labdane diterpenoid forskolin. Specific attention is paid to the utility of forskolin as a biological tool to stimulate adenylyl cyclase and its corresponding analogs as therapeutics. The latter half of Chapter 2 focuses on prior total syntheses of this secondary metabolite, highlighting the challenges associated with constructing the carbocyclic core and establishing the stereochemically complex array of oxidation found in the natural product. Chapter 3 details our synthetic efforts towards forskolin, which leveraged the previously described MHAT-initiated annulation culminating in a 14-step synthesis of the target compound. Chapter 4 begins with a brief overview of the biosynthesis and bioactivity of quassinoid natural products. This section focuses on some of most biologically potent congeners and their antimalarial and anticancer properties. The latter portion of this chapter covers the prior syntheses of the congener quassin, which serves as a logical entry point for groups aiming to establish a general synthetic route to the quassinoids. Specific attention is paid to the challenges associated with introducing the extensive oxidation found in quassin. Chapter 5 details our synthetic efforts towards quassin and the evolution of the MHAT-initiated annulation in a synthetic setting, which led to a 14-step synthesis of the target compound.

Fossils are a promising source of novel drug scaffolds and new drugs, referred to herein as paleopharmaceuticals. Baltic amber, or fossilized resin produced by extinct pines of the family Sciadopityaceae, has been used in traditional medicine to treat a variety of diseases. To explain the medicinal significance of Baltic amber, we report optimized extraction procedures, specifically single rounds of conservative or Soxhlet extraction with dichloromethane. We also present comprehensive surveys of the chemical compositions of Baltic amber and resin from Sciadopitys verticillata, the only extant Sciadopityaceae species. Our analyses using gas chromatography-mass spectrometry showed that Baltic amber and S. verticillata resin are primarily composed of terpenes and terpenoids; however, the identities of these compounds are different because of the chemical transformations that occur during fossilization. The only terpenoid identified in both was verticillol, and this is the first known report of verticillol as a constituent of Baltic amber. Finally, we present in vitro antibacterial activity data for abietane-type diterpenoids like those identified in Baltic amber. These compounds possess significant antibacterial activity against antibiotic-resistant Gram-positive bacterial strains; therefore, abietane-type diterpenoids are a promising drug scaffold for new paleopharmaceuticals.Bacillus anthracis, the causative agent of anthrax, has been identified by the Centers for Disease Control and Prevention as a bioterrorism weapon with significant potential to be a severe threat to public health and safety. Current treatments approved by the Food and Drug Administration for anthrax infections do not target the cause of the lethality and a promising target for the discovery and development of effective anthrax therapeutics: the anthrax toxin lethal factor. While progress has been made toward their development, there are no LF inhibitors currently approved to treat anthrax infections. Recently, we performed an experimental high-throughput screen and identified two compounds with significant LF inhibitory activity. We report the design, synthesis, and evaluation of novel small-molecule LF inhibitors based on these two compounds, increasing their solubility for structural biology studies while maintaining their predicted binding affinities and experimental biological activities.

Terpenoids are an exceptionally large family of natural products, and contain numerous bioactive members that are pharmaceutically important. While most research into terpenoids and their metabolism has thus far occurred in non-fungal organisms, chiefly plants, Basidiomycota (mushroom forming fungi) are well known as prolific producers of bioactive sesquiterpenoids, such as the potent anticancer compounds Illudin M and S. While natural products have traditional been a huge driver of pharmaceutical discovery, this natural abundance is often hampered by very low expression in the native host and slow growth or rarity of the host itself. This drives up financial and environmental costs, and in many cases makes the production of otherwise useful natural products impracticable. One potential solution to this quandary is heterologous production of secondary metabolites in non-native hosts such as Escherichia coli and Saccharomyces cerevisiae. Another avenue is in vitro biocatalysis, wherein the biosynthetic enzymes of the native host are heterologously expressed, isolated, and used to perform synthesis outside of the cell. This approach avoids the fragility of the in vivo system and would allow the creation of combinatorial enzymatic pathways to create novel bioactive structures. With regards to constructing a sesquiterpenoid biosynthetic pathway, many stable terpene synthases have been isolated and shown to be active in vitro. However, the most well studied terpene scaffold modifying enzymes, cytochrome P450s, are notoriously difficult to heterologously express in active form. In order to obtain scaffold modifying oxygenases capable of being part of an in vitro terpenoid biosynthetic pathway, fungal oxygenases aside from cytochrome P450s were investigated. Specifically, unspecific peroxygenase from Agrocybe aegerita and flavin binding oxidoreductases from Δ6-protoilludene biosynthetic gene clusters were expressed and assayed against the sesquiterpene scaffold.

In the first chapter of this dissertation, a three-step total synthesis of the antimalarial (+)-cardamom peroxide, an endoperoxide-containing monoterpene dimer, is reported. This concise synthesis utilized (–)-myrtenal as an inexpensive terpene building block, and applied a novel oxygen stitching strategy to install all the oxygen atoms in the natural product from molecular oxygen. This strategy has enabled the preparation of large quantities of (+)-cardamom peroxide, and subsequent studies have determined its absolute configuration, and this molecule’s reactivity in iron(II)-induced reductive cleavage. Additionally, the antimalarial activities of cardamom peroxide against the clinical isolates of Plasmodium falciparum from several Cambodia provinces have been evaluated.In the second chapter, a double allylation strategy for the construction of the [5,7,5]-fused carbocyclic system found in guaianolide sesquiterpenoids is disclosed. This strategy features a robust intramolecular allylation mediated by tin(II) chloride to assemble the seven-membered core. An efficient and scalable total synthesis of the trans-fused 8,12-guaianolide (+)-mikanokryptin via this strategy is reported in nine to ten steps from the abundant monoterpene (+)-carvone, which constitutes the first example of gram-scale total synthesis of any guaianolide natural product. Subsequently, the oxygen stitching strategy has been expanded from the synthesis of endoperoxides to the strategic installation of multiple oxygen atoms on complex guaianolides in a stereocontrolled manner. A concise total synthesis of (–)-nortrilobolide and a formal synthesis of the anticancer agent (–)-thapsigargin are achieved by merging the oxygen stitching strategy and double allylation strategy.Preliminary studies on a modular synthesis of guaianolides from the Apiaceae family of plants are also disclosed via an intramolecular allylation strategy. These studies include concise total syntheses of sinodielide A and grilactone from chiral-pool building block linalool, and studies towards the total syntheses of prutenin, ammolactone A, and montanolide. Notably, this strategy has the potential to access the Apiaceae guaianolides encompassing all the oxidation levels in this family.