Thesis advisor: Larry W. McLaughlin / Nucleic acids are essential biological molecules that encode and transfer genetic information from generation to generation. Intensive efforts have been made by scientists to study the properties of nucleic acids, looking for opportunities that could help diagnose, prevent, and cure disease, and/or gain a greater insight into the wonder of nature. Chapter 2 presents our synthetic attempts towards the rigidified nucleosides 2'-deoxy-6,3'-propanouridine and 2'-deoxy-6,3'-butanouridine. These nucleosides are constrained so that they mimic the native conformation in DNA duplex and are postulated to increase duplex stability, as well as increase the affinity of the nucleobase for its complementary partner. Chapter 3 presents work towards the synthesis of backbone extended nucleosides. These molecules have the potential to form a new type of helical structure when incorporated into a double helix. Through the investigation of these novel nucleic acids, we would like to gain a greater understanding of the properties that contribute to duplex stability. / Thesis (MS) — Boston College, 2013. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis advisor: Larry W. McLaughlin / Thesis advisor: Mary F. Roberts / Nucleic Acids are unique biopolymers capable of encoding and transferring genetic information from one generation to the next for every form of life. This fascinating property has made them the topic of intense research from a variety of aspects. Some researchers try to understand how life might have started. Some try to elucidate how the whole process works. Some try to use the properties of nucleic acids as a tool for various purposes. The continuous effort over more than a century explored a lot about the structures and functions of nucleic acids. There is a lot to be discovered yet. This work began with the design and development of a new class of nucleoside analogue with the goal to study their ability to bind nucleic acids. The ongoing research will establish their application as therapeutics and as biomolecular tools. Along the way significant effort went into preparing these analogues. New methodology was developed to address some of the unanswered synthetic problems of nucleoside chemistry. / Thesis (PhD) — Boston College, 2012. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis advisor: Abhishek Chatterjee / Noncanonical amino acid (ncAA) mutagenesis provides powerful new ways to probe and manipulate protein function both in vitro and in living cells. Increasing the number of ncAAs that can be site-specifically encoded can greatly expand the scope of this promising technology. We aimed to address the challenges that limit the multisite ncAA incorporation technology in both Escherichia coli and mammalian cells. Our work has significantly expanded the scope of this technology through the development of mutually compatible suppression systems and the optimization of their expression. Using these platforms, we further demonstrate powerful new applications of dual-ncAA incorporation technology both in E. coli and mammalian cells. / Thesis (PhD) — Boston College, 2018. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

In this dissertation, we discuss the development of a synthetic method to functionalize various α-haloglycine esters, as key precursors to a large variety of non-proteinogenic α-amino acids (Xaas). At first, we discovered a very practical and high yielding acetyl chloride-mediated cascade reaction to synthesize α-arylated amino esters in one-pot. In this multicomponent reaction (MCR), a primary carbamate was condensed with a glyoxylate, followed by an in situ halogenation which proved essential to trigger the final Friedel−Crafts functionalization. After careful reaction optimization, a plethora of arene nucleophiles were reacted with high regioselectively in CHCl3 at low temperatures (Method A) while less activated arenes reacted more cleanly in CH3CN and at higher temperatures (Method B). To broaden the scope of this reaction to acid sensitive nucleophiles, a one-pot reaction was designed via evaporation of all acid by-products at the α-haloglycine stage. The anion-binding Schreiner’s thiourea catalyst proved to be extremely efficient to promote this complementary approach (Method C) which relies on the chloride leaving group activation by the catalyst to assist the functionalization stage and deliver the α-amino ester product. In the second chapter, some highly practical and efficient preparations of α-haloglycine esters in one-pot have been developed to generate useful precursors of non-proteinogenic α-amino esters. Also, a mild and unique AcOH(cat.)/AcCl system was found to promote an autocatalytic-like condensation/deoxy halogenation and facilitate the multicomponent assembly of non-proteinogenic α-amino esters. Friedel–Crafts reaction between α-chloroglycine and N-methylindole have been studied in details to understand the mechanistic intricacy of this reaction. Our findings through the initial kinetic profiling support that the arylation likely proceeds via a SN1-like (or SN2C+) mechanism. In third chapter, we discuss the development of the most challenging α,α-disubstituted amino esters in a multicomponent fashion. Our results highlight that the MCR proceeds via the formation of an enamide intermediate, which is further tautomerized to corresponding iminium to produce the desired product. In collaboration with Eli Lilly at the Automated Synthesis Laboratory (ASL), we have developed silver (I) salts mediated Friedel–Crafts reaction for synthesis of α-trifluoromethylated α-amino esters on a fully automatized robot. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2018. / FAU Electronic Theses and Dissertations Collection

Thesis (M.Phil.)--Chinese University of Hong Kong. / Bibliography: leaves 73-84.

The purpose of this thesis was to study the nucleic acids of Capsicum annuum plastids during fruit ripening. The ultrastructural characteristics of Capsicum annuum plastids were studied during the transition between chloroplast and chromoplast, revealing the complex changes in membrane structure. Ploidy changes in ripening plastids was followed using a new experimental system, the Leitz MPV3 microphotometer. The relative changes in fluorescence of DAPI-stained plastids was measured. Chromoplasts proved to contain a UV-absorbing substance which reduced the level of fluorescence. The amount of plastid DNA decreases from leaf chloroplasts to green pepper plastids, and possibly decreases further in the chromoplast. It was concluded that the system was unsuitable for use with plastids of changing pigment content. A ripeness index of pepper fruit was formulated using a general pigment extraction. Ripeness was assessed by the ratio of absorbance measured at 470 and 430nm of this extract. The use of an in vitro ripening system was investigated to counter the problems of availibility and uneven ripening of green-house ripened fruit. Similarity between the chloroplast and chromoplast genome was examined by comparison of Bam Hl digestion patterns. The resolved gel bands were identical. Clones were created containing Capsicum annuum chloroplast DNA using a modified lambda bacteriophage, lambdaL47 vector. The lambdacap clones were investigated using Bam Hl restriction endonuclease digests. The enzyme digests revealed fragments in the 4-8.5kb region, and l8kb upwards. It was concluded that the 4-8.5kb fragments comprised the foreign DNA insertion. Hybridization of chloroplast DNA with lambdacap clones gave low levels of hybridization, which was concluded to be due to impurities in the plastid DNA. Hybridization of lambdacap clones to each other revealed that 17 of the 22 clones are closely related. l6s rRNA extract hybridized with certain lambdacap clones, although clones containing known chloroplast genes for LSU, beta and alpha subunits of ATPase and cytochrome f did not. Collation of this evidence, together with the Bam Hl fragment patterns led to the conclusion that the lambda cap clones map in the small single copy region and part of the inverted repeat region. Study of gene expression during the chloroplast-chromoplast transition was studied by hybridization of RNA, isolated from pepper fruit ripened in vitro, with lambda cap clones. Evidence showed changes in expression accompanied fruit ripening.

Boronic acids are key reagents in a host of chemical applications. In particular, they have been utilised in a range of metal-catalysed coupling reactions, involving the facile formation of carbon-carbon or carbon-heteroatom bonds under mild conditions that often boasts high yields and selectivity, thus becoming a vital tool in the design of complex molecules. Alongside the increased application of boronic acids, there has been a substantial increase in their commercial availability and now a wide range of elaborate boronic acids exist. However, many of these motifs are prone to undesired and troublesome side reactions, namely protodeboronation. Although many efforts have been made towards mitigating decomposition during coupling, the general mechanistic understanding of in situ protodeboronation is remarkably limited and outdated. pH-rate profiles for the protodeboronation of many heterocyclic, vinyl and cyclopropyl boronic acids (1:1 H2O/dioxane, pH 1-13, 70 °C) have been constructed using NMR spectroscopy. A general model was constructed to allow the simulation of pH-rate profiles and allow facile extrapolation of equilibrium and rate constants. With computational support, a range of novel protodeboronation mechanisms have been elucidated. Concentration-dependent processes (self-/auto-catalytic protodeboronation and disproportionation of boronic acid into borinic acid and boranes) are present when both boronic acid and boronate are present in high concentrations. Non-basic heterocyclic, vinyl and cyclopropyl boronic acids display common acid- and base-catalysed protodeboronation mechanisms, however basic heterocyclic boronic acids exhibit additional pathways. The formation and subsequent fragmentation of zwitterion water adducts (particularly for 2-pyridyl, 5-thiazolyl and 5- pyrazolyl boronic acids) leads to surprisingly rapid protodeboronation at neutral pH values, which can be attenuated (2-pyridyl) or accelerated (5-thiazolyl/5-pyrazolyl) with various Lewis acid additives. Protodeboronation of a series of polyfluorophenyl boronic acids under alkaline conditions revealed an immense range of reactivity, spanning several orders of magnitude (phenyl boronic acid, t½ ≈ months; pentafluorophenyl boronic acid, t½ ≈ milliseconds). Ortho-fluorine substituents were found to heavily influence the reactivity of such substrates. Detailed KIE and computational studies indicate the presence of a unique mechanism involving rate-limiting fragmentation of aryl boronate to form an aryl anion intermediate. Strong correlations with LFER and computational parameters indicate this mechanism is predominant with extremely electron deficient or ortho-fluoro substituted substrates, and can be used as a predictive model for the reactivity of aryl and polyfluorophenyl boronic acids.

Digitized by Kansas Correctional Industries

No description available.

No description available.