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Open Access Publications from the University of California

Scholarly Works (26 results)

  • Thesis
  • Peer Reviewed
UC Berkeley Electronic Theses and Dissertations (2018)

The synthesis and absolute stereochemical determination of cycloprodigiosin has been completed. Chapter 1 discusses the historical, synthetic, and biological background of prodiginine natural products, specifically of prodigiosin and cycloprodigiosin. Chapter 2 details our synthetic attempts for the synthesis of cycloprodigiosin and the strategy used to determine the absolute stereochemistry at the C4’ position of this prodiginine. The syntheses of both enantiomers of cycloprodigiosin were completed in an efficient five step sequence utilizing a Barton-Schöllkopf-Zard pyrrole synthesis. Cycloprodigiosin was isolated from its parent bacterial source, Pseudoalteromonas rubra, by Tristan de Rond in a collaboration with the Keasling group at UC Berkeley. The natural isolate was determined to exist as a scalemic mixture in a ratio of 83:17 (R):(S) at C4’. The enzyme responsible for the final oxidative cyclization event from prodigiosin to cycloprodigiosin was identified as the alkylglycerol monooxygenase-like enzyme PRUB680.

The second topic of this thesis details the first total synthesis of ambiguine P in 19 steps from (S)-carvone. The isolation, biosynthentic, and synthetic background of the ambiguine family of natural products is discussed in Chapter 3. The challenges associated with the synthesis of pentacyclic ambiguines are described in Chapter 4 and focus on the formation of the pentacyclic core in addition to the installation of the C12 quaternary center. The 1st generation synthetic approach to access the ambiguine pentacyclic core involves a key γ-enolate cross-coupling reaction to form the tetracyclic precursor. The intermediates in this approach were synthesized from indole and (S)-carvone using an intermolecular Nicholas alkylation. The 2nd generation synthetic route to access the key pentacyclic core involves an intramolecular Nicholas alkylation at C2 of indole, followed by Friedel-Crafts cyclization at C4 to successfully generate the pentacylic core.

Chapter 5 describes the completion of ambiguine P; many strategies were explored to install the C12 quaternary center, and eventually a directed C–C bond construction utilizing formates was found that successfully formed the C–C bond on the desired α-face. The requisite vinyl group at C12 and the amide functionality at C11 were installed using an interrupted Peterson olefination strategy. Attempts are described to access ambiguine L from these late-stage intermediates using benzylic oxidation and hydration methodologies.

    Cover page: The Total Synthesis of Cycloprodigiosin and Synthetic Efforts Toward the Pentacyclic Ambiguine Class of Natural Products
    • Article
    • Peer Reviewed
    UC Davis Previously Published Works (2019)
    Olives are inedible because of high levels of bitter phenolics (e.g., oleuropein) which are removed during commercial olive processing. Current commercial processing methods are highly water-intensive, produce toxic wastewater, and are environmentally unsustainable. To address this, macroreticular polymeric resins were used to assist debittering and decrease water use. Amberlite resins XAD4, XAD16N, XAD7HP, and FPX66 were evaluated for the ability to adsorb bitter and/or high-value phenolic compounds (i.e., oleuropein, ligstroside, oleuropein aglycone, ligstroside aglycone, oleocanthal, oleacein, and hydroxytyrosol) from whole olives during typical brine storage. All resins effectively adsorbed oleuropein and ligstroside. FPX66 reduced oleuropein in whole olives suspended in a 1.0% acetic acid brine to 0.635 mg/kg wet weight in 2.5 months with no further processing. This concentration is below levels measured in commercial California-style black ripe olives (0.975 mg/kg wet weight). Resins in storage brines effectively decrease levels of bitter phenolic compounds without additional lye processing. Excellent recoveries of high-value phenolic compounds are obtained from resins (e.g., 80.2 ± 3.3% to 89.4 ± 8.9% hydroxytyrosol).
      Cover page: Use of Amberlite Macroporous Resins To Reduce Bitterness in Whole Olives for Improved Processing Sustainability
      • Article
      • Peer Reviewed
      UC Davis Previously Published Works (2018)
      Olives are one of the oldest food products in human civilization. Over the centuries, numerous methods have been developed to transform olives from a bitter drupe into an edible fruit. Methods of processing table olives rely on the acid, base, and/or enzymatic hydrolysis of bitter phenolic compounds naturally present in the fruit into nonbitter hydrolysis products. Today, there are three primary methods of commercial table olive processing: the Greek, Spanish, and Californian methods, in addition to several Artisanal methods. This review focuses on the technological, microbiological, chemical, and sensory aspects of table olive processing and the inherent benefits and drawbacks of each method. The table olive industry is facing challenges of environmental sustainability and increased consumer demand for healthier products. Herein, we examine current research on novel technologies that aim to address these issues.
        Cover page: Reducing Phenolics Related to Bitterness in Table Olives
        • Article
        • Peer Reviewed
        UC Davis Previously Published Works (2018)
        Oleuropein, ligstroside, and related hydrolysis products are key contributors to olive bitterness, and several of these phenolics are implicated in the prevention of lifestyle age-related diseases. While table olive processing methods are designed to reduce oleuropein, the impact of processing on ligstroside and related hydrolysis products (e.g., oleacein, oleocanthal, hydroxytyrosol glucoside, ligstroside aglycone, and oleuropein aglycone) is relatively unknown. Herein, levels of these compounds were measured in Spanish-style green (SP), Californian-style black ripe (CA), and Greek-style natural fermentation (GK) olives using rapid ultrahigh-performance liquid chromatography (UHPLC) tandem mass spectrometry (MS/MS). GK olives had the highest concentration of all compounds measured, with the exception of oleocanthal, which was highest in SP olives (0.081 mg kg-1 wet weight (w.wt)). CA olives had the lowest levels of most compounds measured, including ligstroside (0.115 mg kg-1 w.wt) and oleuropein (0.974 mg kg-1 w.wt). Hydroxytyrosol was the predominate compound in all three styles of commercial olives, with similar concentrations observed for GK and SP olives (134.329 and 133.685 mg kg-1 w.wt, respectively) and significantly lower concentrations observed for CA olives (19.981 mg kg-1 w.wt).
          Cover page: Quantitation of Oleuropein and Related Phenolics in Cured Spanish-Style Green, California-Style Black Ripe, and Greek-Style Natural Fermentation Olives
          • Article
          • Peer Reviewed
          UC San Diego Previously Published Works (2014)
          Interdigitating dendritic cell sarcoma (IDCS) and histiocytic sarcoma (HS) are two distinct rare hematolymphoid neoplasms, and HS derived from a likely pre-existing IDCS has never been reported in the English literature. Diagnosis of such entities in excised specimens is difficult, but becomes more difficult with the scant amount of materials obtained with fine needle aspiration (FNA) and core needle biopsy. Here we present an interesting and unique case of an IDCS located within a mesenteric mass, which was initially diagnosed as IDCS from the cytology of FNA and core needle biopsy specimens. After brief chemotherapy, the patient again developed abdominal pain, and a HS was diagnosed based on the excised segmental small intestinal specimen. While the exact relationship between the IDCS and HS cannot be ascertained, it is most likely that the HS is derived from the IDCS, although co-existing HS in addition to IDCS from the cytology specimen cannot be completely ruled out.
            Cover page: A case of interdigitating dendritic cell sarcoma/histiocytic sarcoma--a diagnostic pitfall.
            • Article
            • Peer Reviewed
            UC Berkeley Previously Published Works (2019)
            The first synthesis of a pentacyclic ambiguine (ambiguine P) is reported. The synthesis takes advantage of sequential alkylations of an indole core to rapidly construct the pentacyclic framework of the natural product. Key to the success of the synthesis was the use of a Nicholas reaction to alkylate at C2, crafting a fused seven-membered ring that is characteristic of the pentacyclic ambiguines, as well as the use of an amide-directed functionalization at C12 to set a requisite quaternary center. A versatile late-stage intermediate was prepared that may be applicable to the synthesis of the other pentacyclic ambiguines.
              Cover page: Total Synthesis of Pentacyclic (−)-Ambiguine P Using Sequential Indole Functionalizations
              • Article
              • Peer Reviewed
              UC Berkeley Previously Published Works (2015)
              The enantiomers of the natural product cycloprodigiosin were prepared using an expedient five-step synthetic sequence that takes advantage of a Schöllkopf-Barton-Zard (SBZ) pyrrole annulation with a chiral isocyanoacetate and a nitrocyclohexene derivative. Using chiral HPLC and X-ray crystallographic analyses of the synthetically prepared material and natural isolate (isolated from the marine bacterium Pseudoalteromonas rubra), naturally occurring cycloprodigiosin was determined to be a scalemic mixture occurring in an enantiomeric ratio of 83:17 (R)/(S) at C4'.
                Cover page: Synthesis of Cycloprodigiosin Identifies the Natural Isolate as a Scalemic Mixture
                • Article
                • Peer Reviewed
                UC Davis Previously Published Works (2021)
                Online citizen science projects have broadened options for accessing science and enabled different forms of participation in scientific research for adult and young volunteers. Yet, little is known regarding participation patterns among youth participants. Quantitative approaches were used to investigate the contribution of 183 young volunteers to citizen science on the iNaturalist platform and the participation behaviour that relates to their contribution. The participants accessed and used iNaturalist as part of one-day field-based events (bioblitzes) facilitated by museums. Compared to the observation behaviour of all iNaturalist users, as documented on the platform, the young volunteers observe fewer plants and birds, and more molluscs, arachnids and insects. The average daily contributions of young volunteers were found to be positively associated with a large proportion of active days on iNaturalist and a systematic contribution behaviour, yet negatively related to a long duration on the platform. This study enhances our understanding of young volunteers' contributions to citizen science and provides insights for research on participation in online citizen science. Our findings have implications on how museums design the field-based events to encourage follow-up systematic participation and maintain active contribution.
                  Cover page: Exploring the participation of young citizen scientists in scientific research: The case of iNaturalist
                  • Article
                  • Peer Reviewed
                  UC San Francisco Previously Published Works (2014)
                  Patients with pulmonary hypertension associated with congenital heart disease survive longer with preserved right ventricular (RV) function compared with those with primary pulmonary hypertension. The purpose of this study was to test the hypothesis that superior RV performance can be demonstrated, at baseline and when challenged with increased RV afterload, in lambs with chronic left-to-right cardiac shunts compared with control lambs. A shunt was placed between the pulmonary artery and the aorta in fetal lambs (shunt). RV pressure-volume loops were obtained 4 wk after delivery in shunt and control lambs, before and after increased afterload was applied using pulmonary artery banding (PAB). Baseline stroke volume (8.7 ± 1.8 vs. 15.8 ± 2.7 ml, P = 0.04) and cardiac index (73.0 ± 4.0 vs. 159.2 ± 25.1 ml·min(-1)·kg(-1), P = 0.02) were greater in shunts. After PAB, there was no difference in the change in cardiac index (relative to baseline) between groups; however, heart rate (HR) was greater in controls (168 ± 7.3 vs. 138 ± 6.6 beats/min, P = 0.01), and end-systolic elastance (Ees) was greater in shunts (2.63 vs. 1.31 × baseline, P = 0.02). Control lambs showed decreased mechanical efficiency (71% baseline) compared with shunts. With acute afterload challenge, both controls and shunts maintained cardiac output; however, this was via maladaptive responses in controls, while shunts maintained mechanical efficiency and increased contractility via a proposed enhanced Anrep effect-the second, slow inotropic response in the biphasic ventricular response to increased afterload, a novel finding in the RV. The mechanisms related to these physiological differences may have important therapeutic implications.
                    Cover page: Adaptive right ventricular performance in response to acutely increased afterload in a lamb model of congenital heart disease: evidence for enhanced Anrep effect
                    • Article
                    • Peer Reviewed
                    UC Irvine Previously Published Works (2019)
                    Waterpipe smoking is becoming more popular worldwide and there is a pressing need to better characterize the exposure of smokers to chemical compounds present in the mainstream smoke. We report real-time measurements of mainstream smoke for carbon monoxide, volatile organic compounds and nanoparticle size distribution and chemical composition using a custom dilution flow tube. A conventional tobacco mixture, a dark leaf unwashed tobacco and a nicotine-free herbal tobacco were studied. Results show that carbon monoxide is present in the mainstream smoke and originates primarily from the charcoal used to heat the tobacco. Online measurements of volatile organic compounds in mainstream smoke showed an overwhelming contribution from glycerol. Gas phase analysis also showed that very little filtration of the gas phase products is provided by the percolation of mainstream smoke through water. Waterpipe smoking generated high concentrations of 4-100 nm nanoparticles, which were mainly composed of sugar derivatives and especially abundant in the first 10 min of the smoking session. These measured emissions of volatiles and particles are compared with those from a reference cigarette (3R4F) and represent the equivalent of the emission of one or more entire cigarettes for a single puff of hookah smoke. Considerations related to the health impacts of waterpipe smoking are discussed.
                      Cover page: Chemical characterization of nanoparticles and volatiles present in mainstream hookah smoke
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