<p>  </p> <p>A historically important reaction, the Ueno-Stork reaction promotes, through the use of toxic organotin species, the cyclization of a haloacetal onto an alkene generating bicyclic acetals. This reaction has been used over the years in several total syntheses of biologically relevant natural products, especially the prostaglandin class of natural products. Herein, will be described the development of a novel nickel-catalyzed Ueno-Stork cyclization reaction, which no toxic organotin and radical promoters are used, and instead a greener, operationally friendly, and non-toxic earth abundant nickel catalyst is applied. Optimization studies, substrate scope, scalability, relative stereochemistry of the bicyclic acetals, as well as derivatization of the products were studied. Furthermore, the newly developed reaction was applied on the total synthesis of tricyclic-PGDM Methyl ester, a prostaglandin D2 metabolite of important clinical relevance that currently suffers from material supply issues.</p> <p>Cyclopropanol ring opening reactions have different reactivity modes. Either a metal homoenolate species or a b-keto radical species can be formed after ring opening depending on the reaction conditions applied. More specifically, hydroxycyclopropanols have been studied to access several important motifs present in an array of natural products and medicinally important molecules. The Dai group has used this strategy to access several motifs through intramolecular trapping of the homoenolate species with and without the presence of carbon monoxide to generate oxaspirolactones, THF/THP-fused bicyclic lactones, and disubstituted THF/THP heterocycles. Herein, it will be discussed the application of similar concepts to access new classes of heterocycles 4-ketovalerolactones and 3-furanones. The optimization of two reaction conditions to selectively synthesize each product starting from the same starting material was studied. Furthermore, the substrate scope, scale-up, and derivatization studies of each motif will be disclosed. </p>

Agarwood mainly formed by Aquilaria species is an economically and pharmaceutically important natural product used for the production of incense, perfumes and traditional medicines in Asia. Endophytic bacteria are potentially important in producing pharmaceutical compounds found in the plants. The aim of this research is to isolate, classify and identify major endophytic bacteria groups associated with agarwood of Aquilaria crassna species in Khanh Hoa province, Vietnam. Agarwood samples were collected and surface-sterilized, and total endophytic bacteria were isolated on Tryptic Soy Agar by the spread plate method. Major bacterial groups were classified according to the Bergey’s system. The 16S rRNA gene fragments were amplified using PCR method, and bacterial isolates were identified using this gene sequence similarity based method. The results showed that from 0.121 g of agarwood, total 26 bacterial isolates were purified and divided into 7 separated groups, in which the group II of Gram-positive spore-forming bacteria was the most dominant. Especially, two dominant strains, T14 of group II, and T15 of group VII, were identified as Bacillus pumilus and Alcaligenes faecalis, respectively.!To our knowledge, it is the first time that biodiversity of bacterial endophytes associated with agarwood from Aquilaria crassna in Vietnam has been reported, which requires of further study to understand the relationship of endophytic bacteria to agarwood-producing Aquilaria crassna species as well as explore their potential applications towards the development of valuable bioactive compounds. / Trầm hương, chủ yếu được tạo ra từ các loài cây Dó (Aquilaria), là một sản phẩm tự nhiên có giá trị kinh tế và y học đã được sử dụng để sản xuất hương, nước hoa và các dược phẩm truyền thống ở châu Á. Vi khuẩn nội cộng sinh thực vật được cho là một nguồn quan trọng cho các dược phẩm có nguồn gốc thực vật. Mục tiêu của nghiên cứu này là nhằm phân lập, phân loại và định danh các nhóm vi khuẩn chính trên Trầm hương Khánh Hòa, Việt Nam. Các mẫu Trầm hương được thu nhận và vô trùng bề mặt dùng để phân lập vi khuẩn tổng số trên môi trường TSA bằng phương pháp trải đĩa. Các nhóm vi khuẩn chính được phân loại dựa theo hệ thống chuẩn Bergey. Đoạn gen mã hóa 16S rRNA được khuếch đại bằng phương pháp PCR, và các chủng vi khuẩn được định danh bằng phép so sánh độ tương đồng trình tự của đoạn gen này. Kết quả cho thấy từ 0,121 g mẫu trầm hương, chúng tôi đã phân lập được 26 chủng vi khuẩn và phân chúng vào 7 nhóm chính, trong đó nhóm II bao gồm các vi khuẩn Gram dương sinh bào tử là nhóm chiếm ưu thế nhất. Đặc biệt, có 2 chủng ưu thế là chủng T14 thuộc nhóm II và chủng T15 thuộc nhóm VII đã được định danh tương ứng là Bacillus pumilus và Alcaligenes faecalis.!Đây là nghiên cứu đầu tiên về đa dạng sinh học của các nhóm vi khuẩn chính trên Trầm hương Khánh Hòa. Vì vậy, cần có những nghiên cứu tiếp theo nhằm tìm hiểu mối quan hệ giữa các vi khuẩn nội cộng sinh với cây Dó bầu (Aquilaria crassna) tạo trầm cũng như khai thác những ứng dụng tiềm năng của các vi khuẩn này theo hướng phát triển các hoạt chất sinh học có giá trị.

Baby spinach (Spinacia oleracea L.) is considered to be the one of the extremely nutritious vegetables, rich both in phytochemicals and core nutrients. Nowadays, phytochemicals in plants are raising interest in consumers for their roles in the maintenance of human health. Variation in content of bioactive compounds and core nutrients is the main concern in vegetable production. Factors such as cultural practices specially fertilization, may affect the nutritional and medicinal properties of the plants Therefore, three parallel trials for NPK to investigate the response of baby spinach leaves to nitrogen (N), phosphorus (P) and potassium (K) on chemical composition were conducted, with treatments arranged as follows: 0, 45, 75, 105, 120 kg·ha-1 N and P and 0, 60, 85, 106, 127, 148 kg·ha-1 K in a randomized complete block design (RCBD) with four replications. The results demonstrated that, application of nitrogenous, phosphorus, potassium fertilizers significantly increased the total phenolic content, total antioxidant activity, total flavonoid content and vitamin C while magnesium, iron, zinc and selenium did not exhibit significant response to all treatments applied. The increase in concentrations on total phenolic content, total antioxidant activity, total flavonoid content and vitamin C was observed, reaching maximum at 45 kg·ha-1 N, 75 kg·ha-1 P and 85 kg·ha-1 K. The optimum rates of 45 kg·ha-1 N, 75 kg·ha-1 P, 85 kg·ha−1 K were then used to formulate the NPK treatment combinations as follows: 0, 30: 30: 40, 45:45:60, 60:60:70, 75:75:90 kg·ha-1, arranged in a RCBD with three replicates. The results showed that total phenolic content, total antioxidant activity , total flavonoid content and vitamin C reached maximum in baby spinach leaves at N45:P45:K60 kg·ha-1. / Agriculture and  Animal Health / M. Sc. (Agriculture)

Baby spinach (Spinacia oleracea L.) is considered to be the one of the extremely nutritious vegetables, rich both in phytochemicals and core nutrients. Nowadays, phytochemicals in plants are raising interest in consumers for their roles in the maintenance of human health. Variation in content of bioactive compounds and core nutrients is the main concern in vegetable production. Factors such as cultural practices specially fertilization, may affect the nutritional and medicinal properties of the plants Therefore, three parallel trials for NPK to investigate the response of baby spinach leaves to nitrogen (N), phosphorus (P) and potassium (K) on chemical composition were conducted, with treatments arranged as follows: 0, 45, 75, 105, 120 kg·ha-1 N and P and 0, 60, 85, 106, 127, 148 kg·ha-1 K in a randomized complete block design (RCBD) with four replications. The results demonstrated that, application of nitrogenous, phosphorus, potassium fertilizers significantly increased the total phenolic content, total antioxidant activity, total flavonoid content and vitamin C while magnesium, iron, zinc and selenium did not exhibit significant response to all treatments applied. The increase in concentrations on total phenolic content, total antioxidant activity, total flavonoid content and vitamin C was observed, reaching maximum at 45 kg·ha-1 N, 75 kg·ha-1 P and 85 kg·ha-1 K. The optimum rates of 45 kg·ha-1 N, 75 kg·ha-1 P, 85 kg·ha−1 K were then used to formulate the NPK treatment combinations as follows: 0, 30: 30: 40, 45:45:60, 60:60:70, 75:75:90 kg·ha-1, arranged in a RCBD with three replicates. The results showed that total phenolic content, total antioxidant activity , total flavonoid content and vitamin C reached maximum in baby spinach leaves at N45:P45:K60 kg·ha-1. / Agriculture and  Animal Health / M. Sc. (Agriculture)

O morango representa boa fonte de vitamina C, flavonóides e derivados de ácido elágico e tem ampla aceitação pela população brasileira. Os objetivos deste trabalho foram: caracterizar diferentes cultivares quanto aos teores de compostos bioativos, otimizar a metodologia para quantificação do conteúdo de ácido elágico total, purificar e caracterizar estruturalmente os elagitaninos, avaliar sua potencial atividade antiproliferativa, anti-diabetes tipo 2 e anti-hipertensão, estudar a biodisponibilidade desses compostos in vivo. Os resultados demonstraram que existem diferenças significativas nos teores de compostos bioativos entre as cultivares. As melhores condições para determinação dos teores de ácido elágico total foram: extração em acetona 80% e posterior hidrólise com ácido trifluoracético (TFA) 2N a 120 °C por 60 minutos. A precipitação com acetato de itérbio foi o método mais eficiente para a purificação dos elagitaninos. Após administração por gavagem a ratos de um purificado de elagitaninos, nenhum composto foi detectado no plasma e tecidos analisados. / Strawberries are a good source of vitamin C, flavonoids and ellagic acid derivatives and are consumed in Brazil in large quantities. The objectives of the present work were: characterization of different cultivars with respect to the content of bioactive compounds, optimization of the method for quantification of total ellagic acid content, purification and structural identification of ellagitannins, evaluation of their antiproliferative, anti-type 2 diabetes and anti-hypertension potentials, investigation of their in vivo bioavailability. The results indicated that there were significant differences in bioactive compounds among the strawberry cultivars. The best conditions for the determination of the total ellagic acid content in strawberries were extraction with 80% acetone, and hydrolysis using 2N TFA at 120 &#176;C for 60 minutes. The precipitation method using ytterbium acetate was the most efficient in purifying the ellagitannins. After administration of purified ellagitannins to rats by gavage, no compound was detected in plasma or tissue samples analyzed.

Submitted by Angela Maria de Oliveira (amolivei@uepg.br) on 2019-03-07T12:00:31Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Sandra Mara Wolff Campelo.pdf: 2947865 bytes, checksum: 60d712c905ba3cbd53cb55587b7d53bf (MD5) / Made available in DSpace on 2019-03-07T12:00:31Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Sandra Mara Wolff Campelo.pdf: 2947865 bytes, checksum: 60d712c905ba3cbd53cb55587b7d53bf (MD5) Previous issue date: 2018-11-19 / O amido pode ser obtido mais comumente a partir de milho, trigo, arroz e também de tubérculos e raízes. Mas outras fontes estão sendo estudadas, como amidos extraídos dos gêneros Dioscoreae spp., uma espécie deste gênero estudada com pouca frequência é a Dioscorea bulbifera Linn conhecida também como cará moela. Neste trabalho o amido nativo de D. bulbifera Linn foi obtido e modificados com extrato aquosos e hidroalcoólicos em três concentrações diferentes de erva-mate, Ilex paraguariensis, planta rica em compostos biotivos responsáveis por suas propriedades benéficas a saúde. Através das técnicas como Calorimetria Exploratória Diferencial (DSC), análises reológicas através da análise Viscoamilográfica (RVA), Termogravimetria acoplada ao sistema - Calorimetria Exploratória Diferencial - Espectrometria de Massas (TG-DSC-MS) e morfológicas como o Microscopia Eletrônica de Varredura (MEV), Difratometria de raios X método pó (DRX) e Colorimetria foi possível verificar a interação deste amido de D. bulbifera Linn com os compostos provenientes dos extratos obtidos das folhas de erva-mate. As temperaturas iniciais de gelatinização, dos amidos, com incorporação de 6% de extrato aquoso, e com 6% extrato hidroalcoólicos foram levemente superiores em relação ao amido nativo, quando estudados por DSC. A maior parte das amostras apresentaram valores de Tp e Tc e entalpia de gelatinização próximos ao nativo. Na análise de RVA observou que os picos de viscosidade foram maiores nos amidos modificados com extrato aquosos. A viscosidade final e a tendência a retrogradação aumentaram em relação ao nativo. As imagens MEV não se alteraram, a coloração do amido nativo teve maior tendência ao L* branco que os modificados. Os difratogramas de raios X apresentaram amido tipo “C. Na análise TG-DSC-MS os eventos principais no DSC foram mais intensos nas amostras tratada, assim como os sinais massa-carga detectados, medidos por espectrometria de massa, ocorreram com eventos mais intensos nas amostras tratadas com extratos hidroalcoólicos e no sinal m/z 58 foi detectado em todas as amostras exceto no amido nativo. Evidenciando que houve incorporação dos compostos fenólicos com modificação no perfil dos gases gerados durante a termo decomposição. / Starch can be obtained most commonly from corn, wheat, rice and also tubers and roots. But other sources are being studied, such as starches extracted from the genus Dioscoreae spp., A species of this genus studied infrequently is the Dioscorea bulbifera Linn also known as gizzard. In this work the native starch of D. bulbifera Linn was obtained and modified with aqueous and hydroalcoholic extract in three different concentrations of yerba mate, Ilex paraguariensis, a plant rich in bioactive compounds responsible for its beneficial health properties. Using the techniques such as Differential Scanning Calorimetry (DSC), rheological analysis through the Viscoamilographic (RVA) analysis. Thermogravimetry coupled to the system Differential Scanning Calorimetry - Mass Spectrometry (TG-DSC-MS) and morphological ones such as Scanning Electron Microscopy (SEM), X-ray diffraction method (XRD) and Colorimetry, it was possible to verify the interaction of this starch of D. bulbifera Linn with the extracts obtained from the leaves of yerba mate. Initial gelatinization temperatures of the starches with 6% aqueous extract incorporation and with 6% hydroalcoholic extract were slightly higher in relation to the native starch when studied by DSC. Most of the samples presented values of Tp and Tc and gelatinization enthalpy near to the native one. In the RVA analysis it was observed that the peaks of viscosity were higher in modified starches with extract aqueous. The final viscosity and tendency to retrograde increased relative to the native. SEM images did not change, native starch staining had a greater tendency to white L * than those modified. The X-ray diffractograms showed starch type "C. In the TG-DSC-MS analysis the main events in the DSC were more intense in the treated samples, as well as the mass-load signals detected, measured by mass spectrometry, occurred with more intense events in the samples treated with hydroalcoholic extracts and in the m / z 58 was detected in all samples except native starch. Evidence that there was incorporation of the phenolic compounds with modification in the profile of the gases generated during the decomposition.

[Truncated abstract] Antimicrobial growth promoters are added to feed to prevent lactic acidosis in ruminant animals by selectively inhibiting rumen bacteria that produce lactic acid. However, recently imposed or impending bans on the use of antimicrobial growth promoters in animal production have lead to a critical need to find practical alternatives that are safe for the animal and consumer and that obtain similar production benefits. I investigated bioactive plants of Australia for their potential to prevent lactic acidosis in ruminants. The unifying hypothesis tested was that plants would be identified that selectively inhibit lactic acid-producing bacteria and consequently protect against lactic acidosis. This hypothesis was tested in a three phase process: phase 1, plant selection and collection; phase 2, a three stage protocol for screening plants and essential oils; phase 3, in vivo experiments and chemical fractionation of the most promising plant. I developed an in vitro bioassay that simulated acidosis by adding glucose to rumen fluid in Bellco tubes and incubating for 5 h (Chapter 4). The pH and gas production were used as indicators of acidosis and fermentation activity. I used this bioassay to screen ninety-five plants (dried and ground material from 79 species) and ten essential oils and included a negative control (oaten chaff) and a positive control (virginiamycin). One plant, Eremophila glabra, produced a similar pH (5.63) to the positive control (5.43) although it inhibited gas production to a moderate extent (P < 0.05). ... Seven serrulatane diterpenes were identified to be the major secondary metabolites in E. glabra. The metabolites were screened using a broth dilution and microtitre spectrophotometry method and were selective against S. bovis at between 320 and 1077 [mu]g/ mL. The serrulatanes from E. glabra were probably responsible for the activity against acidosis that I observed in vitro, because they selectively inhibited lactateproducing bacteria. It is also possible that a synergy between serrulatanes and possibly other metabolites are responsible for the activity observed in vitro. The results from my experiments support the role that bioactive plants may have to replace the antibiotics that are added to livestock feed. Australian plants were identified containing compounds that were active against the bacterial processes responsible for ruminant acidosis. To my knowledge this is the first work undertaken to identify bioactive plants of Australia for their potential to prevent acidosis. I developed in vitro screening bioassays that targeted key indicators of acidosis. These bioassays enabled me to identify 5 plants from the 104 screened that could potentially control acidosis. One of these plants in particular, E. glabra, showed a level of activity in vitro that was comparable to antibiotic protection against acidosis. The exciting in vitro results were not demonstrated in vivo but only one dose level of E. glabra was used, which was based on the in vitro work. In contrast to the in vitro system the rumen is a continuous flow system with greater complexity and it is possible that the concentration of E. glabra that I used in vivo was not optimum. This places importance on future dose response experiments to confirm the efficacy of E. glabra in vivo.

The principle theme of this thesis was the synthesis of bioactive compounds. To this end, this work was focus on two main projects. The first one, which was carried out in the Department of Chemistry of the University of Girona under the supervision of Dr Montserrat Heras, concerned the synthesis of new unnatural amino acids bearing a pyrimidine ring within their side chain for incorporation into the antimicrobial peptide BP100 following a rational design in order to improve its biological profile. On the other hand, the second chapter of this thesis was developed in collaboration with the Laboratoire de Chimie Organique (ESPCI-ParisTech, Paris, France) under the guidance of Pr Janine Cossy and Dr Arseniyadis. This chapter was centered on the total synthesis of three marine natural products with complex structures and interesting biological activities: acremolide B, (–) bitungolide F and lyngbouilloside. / Aquesta tesi s'ha centrat en la preparació de nous compostos bioactius seguint dues estratègies diferents. El primer projecte es va portar a terme sota la supervisió de la Dra. Montserrat Heras del grup LIPPSO del Departament de Química i ha permés el desenvolupament de noves metodologies per la síntesi de nous aminoàcids no naturals. i el seu ús en la preparació d'anàlegs del pèptid antimicrobià BP100 amb l'objectiu de millorar-ne les propietats biològiques. El segon projecte és fruit de la col•laboració amb la Prof. Janine Cossy i el Dr. Stellios Arseniyadis del "Laboratoire de Chimie Organique" de l'Ecole Superieur de Physique et Chimie Industrielles (ESPCI-ParisTech, Paris, França). I ha permés posar a punt tres estratègies sintètiques convergents i versàtils per l’obtenció de tres productes naturals de gran complexitat estructural i interessants activitats biològiques – l'acremolide B, la bitungolide F i la lyngbouilloside – aïllats recentment del fons marí de diferents punts del món.

Part I of this thesis describes the development of bioactive small molecules of relevance to the study of the apicomlexan parasite Toxoplasma gondii into useful chemical tools. The research includes the target identification and validation studies, using both chemical and biological methods. Chapter 1 provides an overview of chemical genetics with a particular emphasis on methods for the identification of the protein targets of bioactive small molecules. The concept of biochemical protein target identification techniques was introduced with a detailed discussion of interesting applications from the literature. Chapter 2 focuses on the development of a tetrahydro-β-carboline based lead molecule into a chemical tool through target identification studies. The structure activity relationship (SAR) data associated with this core structure, the design of a chemical inducer of dimerisation (CID) and the synthesis of this CID are discussed in detail. Chapter 3 described work done to identify the potential protein target(s) of Conoidin A. Experiments to assess whether Conoidin A can inhibit a proposed target in vitro are also included. Further optimisation of this structural class to develop more potent inhibitors is discussed in the second part of this chapter. Part II of this thesis describes the development of methods for the synthesis of medium-sized ring containing compounds using oxidative fragmentation and rearrangement strategies. Chapter 5 provides an overview of the existing oxidative fragmentation methodology, with an emphasis on the use of oxidative fragmentation reactions for the synthesis of medium-sized ring systems (8-11 ring atoms). Chapter 6 focuses on using the established oxidative fragmentation method in the oxizino carbazolone system to investigate the diasteroselectivity of this reaction. Possible mechanisms for this transformation are investigated and discussed using both chemical and computational methods. An interesting rearrangement reaction has also been observed during this study. Chapter 7 focuses on developing an asymmetric oxidative fragmentation method, for use in the diazabenz[e]aceathrylenes system. Asymmetric oxidative fragmentation reactions using [Ru(pybox)(pydic)] catalysts are discussed. Attempts to optimise the enantiomeric excesses of the reaction by varying reaction conditions and substituents in the substrate are also included.

Thesis (PhD)-- Macquarie University, Division of Environmental and Life Sciences, Dept. of Chemistry and Biomolecular Science. 2006. / Bibliography: p. 229-249. / Ch. 1. Introduction -- ch. 2. An ethnobotanical study with the Kamilaroi and Muruwari Aboriginal communities and relationship building -- ch. 3. Biological assay methods and optimisation -- ch. 4. Ethnopharmacological study of Eremophila sturtii -- ch. 5. Ethnopharmacological study of Exocarpos aphyllus -- ch. 6. General conclusions -- Appendices. / This study covered the documentation of first-hand medicinal plant knowledge of Aboriginal communities in northern New South Wales through the isolation and characterisation of bioactive compounds from Aboriginal medicinal plants. / Mode of access: World Wide Web. / xx, 249 p. col. ill., maps, ports