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Open Access Publications from the University of California

Scholarly Works (21 results)

  • Book
  • Peer Reviewed
FlashPoints (2020)
    Cover page: Figures of the World: The Naturalist Novel and Transnational Form
    • Thesis
    • Peer Reviewed
    UC Berkeley Electronic Theses and Dissertations (2018)

    This dissertation describes the discovery and development of new ruthenium cis-triphosphine coordination complexes and their application towards catalytic functionalization of alcohols, ketones, and alkenes. Ruthenium-mediated transfer dehydrogenation of alcohols and subsequent complex ketone functionalization reactions enable the modification of the structures of complex molecules bearing multiple alcohol functionalities. Alteration of the ruthenium catalyst X-type scaffold generates a coordination complex that activates select amines for the direct Markovnikov hydroamination of terminal alkenes. Unactivated terminal alkenes bearing a diversity of functional groups and limiting amounts of alkene can be employed with acceptable yield. Internal alkenes undergo hydroamination with a selectivity that targets tandem isomerization-hydroamination.

    Chapter 1 surveys ruthenium-catalyzed hydrogenation and borrowing hydrogen chemistry with an emphasis on hydrogen transfer-mediated alcohol functionalization. Possible mechanisms of hydrogen transfer are considered and kinetic and thermodynamic considerations regarding hydrogen transfer and hydrogenation reactions are analyzed. This chapter then presents a survey of direct hydroamination reactions of alkenes with late metals and known hydroamination systems with ruthenium catalysts. Precedent in the fields of hydrogen transfer chemistry and hydroamination is described with an emphasis on the synthetic systems of highest utility or closest analogy to the transformations presented in this thesis. The utility, scope, and mechanism of known hydrogen transfer mediated functionalization reactions and seminal contributions to this field are described

    Chapter 2 presents the discovery and development of a new class of ruthenium cis-trisphosphine complexes bearing triflate ligands which catalyze a diverse array of organic transformations. The synthesis of this class of complexes is described in addition to select stoichiometric reactions of these complexes. This chapter presents the application of newly developed ruthenium catalysts towards the selective dehydrogenation of secondary alcohols in diverse complex polyhydroxylated natural products. The epimerization of select secondary alcohols in complex natural products is described. Several mechanistic experiments are given which support insight into the hydrogen transfer catalysts we have developed. Furthermore, this chapter covers the development of complex ketone functionalization chemistries to convert complex ketones to diverse functionalized complex molecules. In particular the description of chemistries for the incorporation of nitrogen based functional groups into complex ketones are presented.

    Chapter 3 presents the development of a new catalytic hydroamination system of terminal alkenes which tolerates limiting amounts of alkene and which enables the modification of a diverse scope of alkene substrates. The synthesis of a new class of catalysts based on a ruthenium trisphosphine scaffold with triflimide X-type ligands is presented along with their catalytic application. A synthetic route a novel osmium analog of the primary ruthenium scaffold is described. Several mechanistic experiments are presented to interpret the high reactivity of the system relative to previous systems in order to explain how a ruthenium catalyst has an activity that supersedes previous rhodium, iridium, and gold-based systems for hydroamination. Empirical observations including the generation of catalytic quantities of unsaturated intermediates in the hydroamination reaction, the tolerance of diverse solvents of widely varied dielectric properties, and the incorporation of deuterium at numerous locations in the starting materials and products the reaction are analyzed. Nuclear magnetic resonance spectroscopic and X-ray crystallographic studies are shown as preliminary support of a borrowing hydrogen type hydroamination mechanism and to support a preliminary proposal regarding the identity of ruthenium complexes along the catalytic cycle of hydroamination.

      Cover page: Discovery of Ruthenium Tris-phosphine Complexes for Poly-alcohol Functionalization and Alkene Hydroamination
      • Article
      • Peer Reviewed
      UC San Diego Previously Published Works (2003)
      The breaking of the electroweak symmetry, and origin of the associated ``weak scale,'' may be due to a new strong interaction. Theoretical developments over the past decade have led to viable models and mechanisms that are consistent with current experimental data. Many of these schemes feature a privileged role for the top quark, and third generation, and are natural in the context of theories of extra space dimensions at the weak scale. We review various models and their phenomenological implications which will be subject to definitive tests in future collider runs at the Tevatron, the LHC, and future linear electron-positron colliders, as well as sensitive studies of rare processes.
        Cover page: Strong dynamics and electroweak symmetry breaking
        • Article
        • Peer Reviewed
        UC San Diego Previously Published Works (2003)
        Models of spontaneous breaking of electroweak symmetry by a strong interaction do not have fine tuning/hierarchy problem. They are conceptually elegant and use the only mechanism of spontaneous breaking of a gauge symmetry that is known to occur in nature. The simplest model, minimal technicolor with extended technicolor interactions, is appealing because one can calculate by scaling up from QCD. But it is ruled out on many counts: inappropriately low quark and lepton masses (or excessive FCNC), bad electroweak data fits, light scalar and vector states, etc. However, nature may not choose the minimal model and then we are stuck: except possibly through lattice simulations, we are unable to compute and test the models. In the LHC era it therefore makes sense to abandon specific models (of strong EW breaking) and concentrate on generic features that may indicate discovery. The Technicolor Straw Man is not a model but a parametrized search strategy inspired by a remarkable generic feature of walking technicolor, that technivector mesons are light, narrow and decay readily into electroweak vector mesons and photons. While walking technicolor is popular among practitioners, alternatives exist and the Straw Man may not lead to their discovery.
          Cover page: Strong dynamics and electroweak symmetry breaking
          • Article
          • Peer Reviewed
          UC Berkeley Previously Published Works (2017)
          Polyoxygenated hydrocarbons that bear one or more hydroxyl groups comprise a large set of natural and synthetic compounds, often with potent biological activity. In synthetic chemistry, alcohols are important precursors to carbonyl groups, which then can be converted into a wide range of oxygen- or nitrogen-based functionality. Therefore, the selective conversion of a single hydroxyl group in natural products into a ketone would enable the selective introduction of unnatural functionality. However, the methods known to convert a simple alcohol, or even an alcohol in a molecule that contains multiple protected functional groups, are not suitable for selective reactions of complex polyol structures. We present a new ruthenium catalyst with a unique efficacy for the selective oxidation of a single hydroxyl group among many in unprotected polyol natural products. This oxidation enables the introduction of nitrogen-based functional groups into such structures that lack nitrogen atoms and enables a selective alcohol epimerization by stepwise or reversible oxidation and reduction.
            Cover page: Site-selective oxidation, amination and epimerization reactions of complex polyols enabled by transfer hydrogenation
            • Article
            • Peer Reviewed
            UC Santa Cruz Previously Published Works (2019)
            Dual numbers allow for automatic, exact evaluation of the numerical derivative of high-dimensional functions at an arbitrary point with minimal coding effort. We use dual numbers to construct tangent linear and adjoint model code for a biogeochemical ocean model and apply it to a variational (4D-Var) data assimilation system when coupled to a realistic physical ocean circulation model with existing data assimilation capabilities. The resulting data assimilation system takes modestly longer to run than its hand-coded equivalent but is considerably easier to implement and updates automatically when modifications are made to the biogeochemical model, thus making its maintenance with code changes trivial.
              Cover page: Dual number-based variational data assimilation: Constructing exact tangent linear and adjoint code from nonlinear model evaluations.
              • Article
              • Peer Reviewed
              UC Davis Previously Published Works (2020)
              An unsupervised learning method is presented for determining global marine ecological provinces (eco-provinces) from plankton community structure and nutrient flux data. The systematic aggregated eco-province (SAGE) method identifies eco-provinces within a highly nonlinear ecosystem model. To accommodate the non-Gaussian covariance of the data, SAGE uses t-stochastic neighbor embedding (t-SNE) to reduce dimensionality. Over a hundred eco-provinces are identified with the density-based spatial clustering of applications with noise (DBSCAN) algorithm. Using a connectivity graph with ecological dissimilarity as the distance metric, robust aggregated eco-provinces (AEPs) are objectively defined by nesting the eco-provinces. Using the AEPs, the control of nutrient supply rates on community structure is explored. Eco-provinces and AEPs are unique and aid model interpretation. They could facilitate model intercomparison and potentially improve understanding and monitoring of marine ecosystems.
                Cover page: Elucidating ecological complexity: Unsupervised learning determines global marine eco-provinces.
                • Article
                • Peer Reviewed
                UC Berkeley Previously Published Works (2021)
                Hydroamination of alkenes catalyzed by transition-metal complexes is an atom-economical method for the synthesis of amines, but reactions of unactivated alkenes remain inefficient. Additions of N-H bonds to such alkenes catalyzed by iridium, gold, and lanthanide catalysts are known, but they have required a large excess of the alkene. New mechanisms for such processes involving metals rarely used previously for hydroamination could enable these reactions to occur with greater efficiency. We report ruthenium-catalyzed intermolecular hydroaminations of a variety of unactivated terminal alkenes without the need for an excess of alkene and with 2-aminopyridine as an ammonia surrogate to give the Markovnikov addition product. Ruthenium complexes have rarely been used for hydroaminations and have not previously catalyzed such reactions with unactivated alkenes. Identification of the catalyst resting state, kinetic measurements, deuterium labeling studies, and DFT computations were conducted and, together, strongly suggest that this process occurs by a new mechanism for hydroamination occurring by oxidative amination in concert with reduction of the resulting imine.
                  Cover page: Ruthenium-Catalyzed Hydroamination of Unactivated Terminal Alkenes with Stoichiometric Amounts of Alkene and an Ammonia Surrogate by Sequential Oxidation and Reduction
                  • Article
                  • Peer Reviewed
                  UC Irvine Previously Published Works (2021)
                  UCH37, also known as UCHL5, is a highly conserved deubiquitinating enzyme (DUB) that associates with the 26S proteasome. Recently, it was reported that UCH37 activity is stimulated by branched ubiquitin (Ub) chain architectures. To understand how UCH37 achieves its unique debranching specificity, we performed biochemical and Nuclear Magnetic Resonance (NMR) structural analyses and found that UCH37 is activated by contacts with the hydrophobic patches of both distal Ubs that emanate from a branched Ub. In addition, RPN13, which recruits UCH37 to the proteasome, further enhances branched-chain specificity by restricting linear Ub chains from having access to the UCH37 active site. In cultured human cells under conditions of proteolytic stress, we show that substrate clearance by the proteasome is promoted by both binding and deubiquitination of branched polyubiquitin by UCH37. Proteasomes containing UCH37(C88A), which is catalytically inactive, aberrantly retain polyubiquitinated species as well as the RAD23B substrate shuttle factor, suggesting a defect in recycling of the proteasome for the next round of substrate processing. These findings provide a foundation to understand how proteasome degradation of substrates modified by a unique Ub chain architecture is aided by a DUB.
                    Cover page: Branched ubiquitin chain binding and deubiquitination by UCH37 facilitate proteasome clearance of stress-induced inclusions
                    • Article
                    • Peer Reviewed
                    UC San Francisco Previously Published Works (2018)
                    Eukaryotic cells employ the ribosome-associated quality control complex (RQC) to maintain homeostasis despite defects that cause ribosomes to stall. The RQC comprises the E3 ubiquitin ligase Ltn1p, the ATPase Cdc48p, Rqc1p, and Rqc2p. Upon ribosome stalling and splitting, the RQC assembles on the 60S species containing unreleased peptidyl-tRNA (60S:peptidyl-tRNA). Ltn1p and Rqc1p facilitate ubiquitination of the incomplete nascent chain, marking it for degradation. Rqc2p stabilizes Ltn1p on the 60S and recruits charged tRNAs to the 60S to catalyze elongation of the nascent protein with carboxy-terminal alanine and threonine extensions (CAT tails). By mobilizing the nascent chain, CAT tailing can expose lysine residues that are hidden in the exit tunnel, thereby supporting efficient ubiquitination. If the ubiquitin-proteasome system is overwhelmed or unavailable, CAT-tailed nascent chains can aggregate in the cytosol or within organelles like mitochondria. Here we identify Vms1p as a tRNA hydrolase that releases stalled polypeptides engaged by the RQC.
                      Cover page: Vms1p is a release factor for the ribosome-associated quality control complex
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