Research efforts towards realizing electrochemically-stable organic semiconductors have been a focus of the organic light-emitting diode (OLED) industry for decades. This is especially true for the discovery of blue-light emitting materials and compounds with optical band gaps greater than 2.8 eV as these materials undergo rapid degradation resulting in poor operational lifetimes. Benzo[1,2-d:4,5-d']bis(oxazole)s and benzo[1,2-d:4,5-d']bis(oxazole)s (BBOs) are useful building blocks that generate highly fluorescent materials with robust thermal and photo-oxidative stabilities and optical band gaps >2.8 eV. Previously, the Jeffries-EL group has synthesized and studied polymeric BBO systems for OLED application, which achieved sky-blue electroluminescence (EL) with external quantum efficiencies (EQEs) of approximately 1.1 %. However, these systems are plagued with broad electroluminescence due to their polydispersity and have yet to achieve power efficiencies >10 lm/W. Small molecule BBO-based emitters (SM-BBOs) are advantageous due to their discrete size, uniform pi-electron delocalization, and high purity. To date, SM-BBOs have realized deep blue EL with good color purity and EQEs approaching 3%. However, the number of possible structural variants are vast, but known examples of these systems are limited, thus more work is required to increase our understanding of these systems to develop SM-BBOs-based OLEDs with higher efficiencies for commercial utility. Herein, several classes of SM-BBOs bearing various aryl substituents are computationally and experimentally studied to understand fundamental optical and electronic properties. This data is used to determine the structure-property relationships between SM-BBO systems and to design functional microelectronic OLEDs. The collected experimental data is used by our computational teams to improve our predictive strategies and refine synthetic efforts. As such, several SM-BBOs were achieved which produced near-UV and deep-blue EL while combinations of these products were used to obtain the first prototype white OLEDs with temperature tunability using SM-BBO emissive materials. / 2022-09-07T00:00:00Z

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第20411号 / 工博第4348号 / 新制||工||1674(附属図書館) / 京都大学大学院工学研究科合成・生物化学専攻 / (主査)教授 杉野目 道紀, 教授 村上 正浩, 教授 中尾 佳亮 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

<p>Natural products, along with natural product derivatives, are known to be at the root of the development of many pharmaceuticals, oftentimes showing unique bioactivity against interesting targets. Specifically, natural products containing furans show activity against a variety of diseases including fungal infections, and cancers. It is hypothesized that unknown natural products containing furans could show more potent or other biological activities. However, it is challenging to discover and isolate these small molecules from cell supernatant. The work described herein showcases the development of a molecular probe that can covalently attach to furan moieties via a [4 + 2] Diels-Alder cycloaddition, making them easily identifiable on liquid chromatography mass spectroscopy (LC-MS). The molecular probe, which undergoes this reaction with a variety of furans, was designed with both a UV-tag and a mass tag to enable easy identification. The probe has been tested with a variety of purified furans, including natural products, methylenomycin furan (MMF) hormones, and MMF derivatives. Moreover, work has begun to test the molecular probe in cell supernatants. </p>

First isolated in 1948 from the Trichothecium roseum fungus, trichothecenes are a diverse class of sesquiterpene natural products with the structures of over 250 congeners established to date. Their general structure consists of the tricyclic “trichothecene” core, marked by the C12,13 exocyclic epoxide and C9,10 olefin, with further structural complexity generated through esterification of macrolide chains to afford macrocyclic trichothecenes including verrucarin A. Owing to their complex structures and potent anticancer activity, trichothecenes have captured the attention of numerous academic groups since the 1970s, resulting in total syntheses of both non-macrocyclic and macrocyclic trichothecenes. The macrocyclic compounds exhibit increased potency, with recent biological studies suggesting involvement of novel molecular targets. The dissertation research described herein is focused on efforts toward the total synthesis of (–)-verrucarol, the flagship trichothecene natural product, and related trichothecene congeners. (–)-Verrucarol was the subject of six total syntheses throughout the 1980s, serving as an entry point for macrocyclic trichothecenes including verrucarin A. Compelled by the recent literature on insight into their therapeutic activity, we have established a concise route to the trichothecene core of verrucarol in eight steps. The construction of the tricyclic system is enabled by a novel samarium (II) iodide (SmI2)-mediated radical cyclization to an enol sulfonate to generate a complex oxabicyclo[3.2.1]octanone ring system. Significant synthetic efforts focused on a key late-stage olefin isomerization, which was ultimately accomplished through Mukaiyama-hydration and elimination. Furthermore, while significant synthetic efforts have gone into constructing the tricyclic trichothecene core, only a single successful, albeit lengthy, enantioselective synthesis of (–)-verrucarol has been reported. To evaluate the full therapeutic potential of trichothecenes, a concise asymmetric synthesis to access the prerequisite tricyclic core is needed. Herein, we report a Cr (III)-salen complex-mediated Diels-Alder cycloaddition of 4-pyrones and the simple diene, isoprene, for rapid access of an enantioenriched precursor for the trichothecene core. Future efforts and synthetic strategies to generate macrocyclic analogues for structure-activity-relationship studies are provided, as focused synthetic efforts to evaluate their clinical potential are sorely needed. / 2025-09-20T00:00:00Z

No description available.

The pheromones are elegant and safe tool for controlling insects and it is possible to control their populations through the manipulation of communication between them, without adversely affecting other beneficial organisms. Pheromones may be involved in various behavioral activities such as food foraging, reproduction, the warning signal in the presence of predators and as chemical defense substances. Hundreds of pheromones and semiochemicals are known and useful for monitoring the presence and abundance of insects and to protect plants against insects and animals. In Brazil, almost all of the products used for this purpose are not produced here. Progress in agriculture is not being accompanied by the provision of inputs to the farmer. With this finding work in the development of pheromones for pest control, new ways of synthesis, formulation, immobilization and controlled release. The work on the synthesis and formulation of pheromones oviposition Culex quinquefasciatus: (5RS, 6S, R)-6-acetoxy-5 hexadecanolídeo via a semi-biotechnological towards a natural source of the acid (Z)-5-hexadecenoic in "scale up" reactions for the synthesis of the pheromone, sordidina, 2,8-dioxy-1-ethyl-3 ,5,7-Trimethylbicyclo [3.2.1] octane, the pheromone of Cosmopolites sordidus in banana boy, synthesis and formulation for the components of the pheromone Metamasius hemipterus alcohols (±)-2-methyl-4-octanol, (±)-2-methyl-4-heptanol, (±)-4-methyl-5-nonanol, (±) - 5-nonanol with the use of a Grignard reaction, synthesis of the main component of the sex pheromone of the moth Tuta absoluta ethyl (3E, 8Z, 11Z) -3,8,11-tetradecatrienila. Was explored alternative semi-biotechnological to obtain materials for the synthesis of (3E, 8Z, 11Z)-6-acetoxy-5 hexadecanolídeo and sordidina, 2,8-dioxy-1-ethyl-3, 5,7 Trimethylbicyclo-[3.2.1] octane. For the controlled release of pheromone work the development and application of microporous biomaterial chitosan and crosslinked chitosan. The pheromone oviposition Culex quinquefasciatus: (5RS, 6S, R)-6-acetoxy-5 hexadecanolídeo was obtained in low yield, the sordidina, 2,8-dioxy-1-ethyl-3 ,5,7-Trimethylbicyclo [3.2 .1] octane was obtained in good yield with a change in route of obtaining an intermediary facilitating and reducing the product cost. The components of the pheromone Metamasius hemipterus, alcohols (±)-2-methyl-4-octanol, (±)-2-methyl-4-heptanol, (±)-4-methyl-5-nonanol, (±) - 5-nonanol were obtained using a Grignard reaction in high yield. Synthesis of ethyl (3E, 8Z, 11Z) -3,8,11 tetradecatrienila was performed by a conventional synthetic route. The releasing chitosan was obtained with the crosslinked chitosan was effective in the release of pheromones. / CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico / Os feromônios são ferramentas elegantes e seguras para o controle de insetos e é possível controlar suas populações através da manipulação da comunicação entre eles sem afetar adversamente outros organismos benéficos. Os feromônios podem estar envolvidos em atividades comportamentais diversas como a procura por alimento, a reprodução, o sinal de alerta na presença de predadores e como substâncias de defesa química. Centenas de feromônios e semioquímicos são conhecidos e úteis para monitorar a presença e abundância de insetos e para proteger as plantas e animais contra os insetos. No Brasil a quase totalidade dos produtos utilizados para este fim não são produzidos aqui. O avanço na agricultura não está sendo acompanhado pela oferta de insumos para o produtor agrícola. Com esta constatação trabalhamos no desenvolvimento de feromônios para controle de pragas, novos caminhos de síntese, formulação, imobilização e liberação controlada. O trabalho realizado na síntese e formulação dos feromônios de oviposição do Culex quinquefasciatus: (5RS,6S,R)-6-acetoxi-5 hexadecanolídeo por uma via semi-biotecnológica visando uma fonte natural do ácido (z)-5-hexadecenóico, no “scale up” de reações para a síntese do feromônio, sordidina, 2,8-dioxi-1-etil-3,5,7-trimetilbiciclo[3.2.1]octano, o feromônio do moleque da bananeira Cosmopolites sordidus, síntese e formulação para os componentes do feromônio do Metamasius hemipterus os álcoois (±)-2-metil-4-octanol, (±)-2-metil-4-heptanol, (±)-4-metil-5-nonanol, (±)-5-nonanol com o uso de reação de Grignard, sintese do principal componente do feromônio sexual da mariposa Tuta absoluta o acetato de (3E,8Z,11Z)-3,8,11-tetradecatrienila com a tentativa de obtenção de intermediário importante de fonte natural e na preparação de liberadores eficientes para os feromônios. Foi explorada a alternativa semi-biotecnologica para a obtenção de materiais para a síntese do : (3E,8Z,11Z)-6-acetoxi-5 hexadecanolídeo e da sordidina, 2,8-dioxi-1-etil-3,5,7-trimetilbiciclo[3.2.1]octano. Para a liberação controlada de feromônio trabalhamos o desenvolvimento e aplicação de biomaterial microporoso a quitosana e quitosana reticulada. O feromônio de oviposição do Culex quinquefasciatus: (5RS,6S,R)-6-acetoxi-5 hexadecanolídeo foi obtido com rendimento baixo, a sordidina, 2,8-dioxi-1-etil-3,5,7-trimetilbiciclo[3.2.1]octano foi obtida em um bom rendimento com alteração na rota de obtenção de um intermediário facilitando e reduzindo o custo do produto. Os componentes do feromônio do Metamasius hemipterus, os álcoois (±)-2-metil-4-octanol, (±)-2-metil-4-heptanol, (±)-4-metil-5-nonanol, (±)-5-nonanol foram obtidos com o uso de reação de Grignard em alto rendimento. A síntese do acetato de (3E,8Z,11Z)-3,8,11 tetradecatrienila foi realizada por uma rota sintética convencional. O liberador obtido foi a quitosana sendo que a quitosana reticulada mostrou ser efetiva na liberação dos feromônios.

Malonyl-thioesters are reactive at the thioester carbonyl and the carboxylate moieties, as seen in acyl transfer or hydrolysis and decarboxylation. Enzymes use these reactive centers to perform different enzyme chemistry throughout metabolism. This enzyme chemistry coupled with the inherent reactivity of malonyl-thioesters makes structure-function studies difficult. When malonyl-thioesters are used for structure-function studies, it usually results in a hydrolyzed or decarboxylated product. There are examples, however, where this is overcome, many of which are discussed throughout this thesis. To overcome the inherent reactivity of malonyl-thioesters and enzymes, analogs have been synthesized to perform structure-function studies. Initial studies focused on altering the thioester carbonyl to limit hydrolysis and decarboxylation; however, these studies revealed the importance of retaining the thioester carbonyl to be positioned in the oxyanion hole. My thesis work focused on the synthesis, characterization, and use in structure-function studies of malonyl-thioester analogs that either preserve the thioester carbonyl or alter it to an ester or amide, and alter the carboxylate to a sulfonate or nitro group. After synthesizing the methylmalonyl-CoA analogs, we performed structure-function studies with methylmalonyl-CoA decarboxylase. This case study revealed the potential of these analogs to both inhibit decarboxylase activity and their use in structure-function studies to gain mechanistic insights. This successful study prompted us to continue these structure-function studies in enzymes with different chemistries such as an epimerase or bi-functional acyltransferase/decarboxylase. The widespread use of these methylmalonyl-CoA analogs also motivated us to add more malonyl-thioester analogs to our toolbox. I have preliminary data that these malonyl-thioester analogs inhibit β-keto-acyl-synthase III, an enzyme involved in fatty acid production in <i>E. coli</i>. This inhibition gives us confidence that these analogs will be useful in structure-function studies that will reveal answers to long standing mechanism and protein-protein interaction questions in the polyketide and fatty acid synthase field.

This thesis is comprised of two parts. The first part describes the synthesis of cyclopentadienyltungsten complexes containing a pendant alkyne group (I), and the subsequent photo-induced intramolecular coordination of the alkyne, forming complexes such as II. Compounds containing intramolecularly coordinated alkynes are rare, and this is the first example using cyclopentadiene as the core ligand. The second part describes the synthesis and structural characterisation of a number of novel metal complexes containing N-heterocyclic carbene ligands, some containing particular functionality for taylored applications. New methods were used to form complexes of rhodium, iridium, silver and gold (eg. III, IV). Structural and spectroscopic properties of the complexes were correlated with electronic characteristics of the ancillary ligands. A number of rhodium and iridium complexes (eg. IV) derived from imidazolium-linked cyclophanes were synthesised and structurally characterised. Complexes of N-heterocyclic carbenes with pendant ionic groups were synthesised, and a preliminary examination of their catalytic activity in water was performed. N-Heterocyclic carbenes complexes containing an electron withdrawing nitro group were synthesised and the effect of the nitro group on metal-ligand bonding was examined.