Os alcalóides ergolínicos são uma categoria de compostos que possuem um esqueleto tetracíclico [6,5,6,6] derivados da ergolina. Do ponto de vista farmacológico, estes compostos são uma classe de produtos naturais importantes, já que exibem uma grande variedade de atividade biológica. Estas moléculas têm sido alvos sintéticos devido ao seu complexo esqueleto tetracíclico e as propriedades supracitadas, o que resultou no desenvolvimento de sínteses totais ao longo do tempo. O ácido lisérgico é o representante notável da família dos alcaloides ergolínicos, uma vez que desde o ano de 1956 até 2013 foram desenvolvidas treze sínteses totais do mesmo. Por isso, o nosso grupo de pesquisa propõe uma rota sintética para a construção de um intermediário indólico-piperidinico, que será usado para realizar a síntese total estereosseletiva do ácido lisérgico em um trabalho de pesquisa futuro. A estratégia para a síntese do intermediário baseia-se na reação de Horner-Wadsworth-Emmons (HWE) e na reação de inserção N-H intramolecular a partir de um aminoaldeído derivado do L-triptofano. A rota sintética inicia-se a partir da elaboração do reagente de olefinação de HWE em três etapas: reação de Michaelis Becker, hidrogenólise catalítica e formação do diazofosfonato. A construção do aminoaldeído requer cinco etapas: esterificação, proteção com Boc, desproteção seletiva, redução do éster e oxidação de Swern. O reagente de olefinação e o aminoaldeído reagem através da reação HWE, fornecendo a diazocetona α, β -insaturada com configuração preferencial Z (Z:E=10:1). Finalmente a olefina Z reage mediante a reação de inserção N-H intramolecular, para fornecer o intermediário indólico-piperidínico. Adicionalmente, desenvolveu-se outra rota para construir o intermediário mencionado através da construção de um derivado de 4-nitroindol, porém esta não foi reprodutível. A síntese do intermediário indólico-piperidínico foi feita em sete etapas, partindo do L-triptofano com rendimento global de 14.9 %. / The ergot alkaloids are a class of compounds which have the tetracyclic skeleton [6,5,6,6] found in the ergoline molecule. These compounds are an important class of natural products that have wide biological activities. They have also been important synthetic targets due to their challenging tetracyclic skeleton as well as due to the previously mentioned biological properties. Lysergic acid is the main representative of the family of ergot alkaloids. Since 1956, thirteen total syntheses have been developed for this alkaloid. Considering the importance of lysergic acid and of the ergot alkaloids, our research group decided to propose a synthetic route to construct an advanced indole-piperidinic intermediate, which may be used to perform the total synthesis of lysergic acid and derivatives in a future work. The strategy to the synthesis of this advanced intermediate is based on the Horner-Wadsworth-Emmons reaction (HWE) and the intramolecular N-H insertion reaction, starting from a L-tryptophan aminoaldehyde derivative. The synthetic route started with the elaboration of the HWE olefination reagent in three steps: Michaelis Becker reaction, hydrogenolysis and diazophosphonate formation. In continuation, the construction of the aminoaldehyde required five steps: esterification, Boc protection, selective deprotection, ester reduction and Swern oxidation. The olefination reagent and the aminoaldehyde reacted by the HWE reaction furnishing an α, β -unsaturated diazoketone with Z configuration (Z:E = 10:1). Finally the Z isomer reacted by means of an intramolecular N-H insertion reaction to provide the indole-piperidine intermediate. Additionally, we developed another route to construct a 4-nitro-indole intermediate, but this was not reproducible. The synthesis of the indole-piperidine intermediate was carried out in seven steps starting from L-tryptophan, with an overall yield of 14.9%.

Pumiliotoxinas e seus congêneres são compostos isolados da pele de algumas espécies de sapos das famílias Dendrobatidae, Mantellidae, Bufonidae, e Myobatrachidae, apresentando interessantes propriedades farmacológicas. As pumiliotoxinas, embora tóxicas, apresentam consideráveis atividades cardiotônicas, assim, acredita-se que as homopumiliotoxinas, as desmetilpumiliotoxinas e as desidrodesmetilpumiliotoxinas também devam apresentar. Nesse sentido, a síntese destes compostos é de extrema valia para a comunidade científica. As diazocetonas α,β-insaturadas são intermediários promissores para a síntese rápida e eficiente de diversos tipos de esqueletos químicos, entre eles, a construção do esqueleto indolizidínico presentes nas pumiliotoxinas. Cabe ressaltar que para as diazocetonas α,β-insaturadas com geometria Z provenientes de amino aldeídos, elas já apresentam a estereoquímica correta para uma direta ciclização para a construção de esqueletos indolizidínicos. Dessa forma, as etapas chaves do trabalho consistiram na preparação de amino aldeídos N-protegidos, na avaliação da reação de Horner-Wadsworth-Emmons para fornecer as diazocetonas α,β-insaturadas com geometria Z, e na reação de inserção N-H intramolecular para a obtenção do ciclo indolizidínico. Outra parte do trabalho consistiu na síntese de imino açúcares de esqueleto piperidínico com cadeias laterais alifáticas (aplicação na química medicinal) e da (-)-1deoxi-altronojirimicina, utilizando-se a mesma metodologia (uso de diazocetonas α,β-insaturadas com geometria Z). / Pumiliotoxins and their congeners are a class of compounds isolated from the skin of some frogs from the Dendrobatidae, Mantellidae, Bufonidae, e Myobatrachidae families, possessing interesting pharmacological activities (cardiotonic activity in low concentrations). Because of the big number of compounds among these toxins (about 100), synthetic methodologies that provide the preparation of these compounds (as well as analogues) in great amounts and in a fast and efficient way using common intermediates, are very important for application in chemical-biology. The α,β-unsaturated diazoketones are promising intermediates for the rapid and efficient synthesis of a range of chemical skeletons, among them, the construction of indolizidine skeleton that pumiliotoxins present. It is important to note that α,β-unsaturated diazoketones with Z geometry (prepared from amino aldehydes) have already the correct stereochemistry for a direct cyclization to construct indolizidine skeletons. The key steps of the work consisted in the preparation of N-protected amino aldehydes, evaluation of Horner-Wadsworth-Emmons reaction in order to obtain α,β-unsaturated diazoketones with Z geometry, and the intramolecular N-H insertion reaction to provide the indolizidine cycle. Another part of the work consisted in the synthesis of iminosugars with piperidine core and aliphatic side chains (application in medicinal chemistry) and in the synthesis of (-)-1-deoxy-altronojirimycin, applying the same methodology (use of α,β-unsaturated diazoketones with Z geometry).

Originally presented as the author's thesis, Columbia University. / Includes bibliographical references (p. 246-249).

Originally presented as the author's thesis, Columbia University. / Includes bibliographical references (p. 246-249).

Os alcalóides ergolínicos são uma categoria de compostos que possuem um esqueleto tetracíclico [6,5,6,6] derivados da ergolina. Do ponto de vista farmacológico, estes compostos são uma classe de produtos naturais importantes, já que exibem uma grande variedade de atividade biológica. Estas moléculas têm sido alvos sintéticos devido ao seu complexo esqueleto tetracíclico e as propriedades supracitadas, o que resultou no desenvolvimento de sínteses totais ao longo do tempo. O ácido lisérgico é o representante notável da família dos alcaloides ergolínicos, uma vez que desde o ano de 1956 até 2013 foram desenvolvidas treze sínteses totais do mesmo. Por isso, o nosso grupo de pesquisa propõe uma rota sintética para a construção de um intermediário indólico-piperidinico, que será usado para realizar a síntese total estereosseletiva do ácido lisérgico em um trabalho de pesquisa futuro. A estratégia para a síntese do intermediário baseia-se na reação de Horner-Wadsworth-Emmons (HWE) e na reação de inserção N-H intramolecular a partir de um aminoaldeído derivado do L-triptofano. A rota sintética inicia-se a partir da elaboração do reagente de olefinação de HWE em três etapas: reação de Michaelis Becker, hidrogenólise catalítica e formação do diazofosfonato. A construção do aminoaldeído requer cinco etapas: esterificação, proteção com Boc, desproteção seletiva, redução do éster e oxidação de Swern. O reagente de olefinação e o aminoaldeído reagem através da reação HWE, fornecendo a diazocetona α, β -insaturada com configuração preferencial Z (Z:E=10:1). Finalmente a olefina Z reage mediante a reação de inserção N-H intramolecular, para fornecer o intermediário indólico-piperidínico. Adicionalmente, desenvolveu-se outra rota para construir o intermediário mencionado através da construção de um derivado de 4-nitroindol, porém esta não foi reprodutível. A síntese do intermediário indólico-piperidínico foi feita em sete etapas, partindo do L-triptofano com rendimento global de 14.9 %. / The ergot alkaloids are a class of compounds which have the tetracyclic skeleton [6,5,6,6] found in the ergoline molecule. These compounds are an important class of natural products that have wide biological activities. They have also been important synthetic targets due to their challenging tetracyclic skeleton as well as due to the previously mentioned biological properties. Lysergic acid is the main representative of the family of ergot alkaloids. Since 1956, thirteen total syntheses have been developed for this alkaloid. Considering the importance of lysergic acid and of the ergot alkaloids, our research group decided to propose a synthetic route to construct an advanced indole-piperidinic intermediate, which may be used to perform the total synthesis of lysergic acid and derivatives in a future work. The strategy to the synthesis of this advanced intermediate is based on the Horner-Wadsworth-Emmons reaction (HWE) and the intramolecular N-H insertion reaction, starting from a L-tryptophan aminoaldehyde derivative. The synthetic route started with the elaboration of the HWE olefination reagent in three steps: Michaelis Becker reaction, hydrogenolysis and diazophosphonate formation. In continuation, the construction of the aminoaldehyde required five steps: esterification, Boc protection, selective deprotection, ester reduction and Swern oxidation. The olefination reagent and the aminoaldehyde reacted by the HWE reaction furnishing an α, β -unsaturated diazoketone with Z configuration (Z:E = 10:1). Finally the Z isomer reacted by means of an intramolecular N-H insertion reaction to provide the indole-piperidine intermediate. Additionally, we developed another route to construct a 4-nitro-indole intermediate, but this was not reproducible. The synthesis of the indole-piperidine intermediate was carried out in seven steps starting from L-tryptophan, with an overall yield of 14.9%.

By tracing the development of the epic, oral and written, as in Chapter III, the qualities that are characteristic of the epic and the devices associated with the epic through continued usage were found to be the constant factors upon which the definition of the epic is formulated. The application to Hiawatha of the epic definition in terms of form, theme, subject matter, characters, tone, the use of the supernatural, and the use of characteristic devices, strengthens the thesis that Longfellow has written an epic.

Small rings are frequently found in natural products as well as incorporated into drugs and agrochemicals in which they impart valuable properties on the biological activity of these compounds. Cyclopropanes are also extremely useful as reagents in organic synthesis, in particular as “umpolung” reagents, allowing access to products which would otherwise be more difficult to synthesise. This thesis will describe forays into the synthesis and further substitution of small rings as well as the iminium-catalysed ring-opening of cyclopropanes. The introduction will outline the uses and properties of cyclopropanes, and will also describe some of the more common ways for incorporating cyclopropanes into larger structures. This will include the Horner–Wadsworth–Emmons procedure which has previously been developed by the group. The second chapter describes efforts towards the iminium-catalysed nucleophilic ring-opening of cyclopropanes. This is followed by Chapter 3, in which the Horner–Wadsworth–Emmons methodology for the synthesis of the cyclopropanes used in Chapter 2 is investigated as a procedure for the synthesis of 4-membered heterocycles. Chapter 4 describes the development of a decarboxylative method for the protodecarboxylation of cyclopropanecarboxylic acids. This was developed as the first step towards decarboxylative cross-coupling of cyclopropanes. Decarboxylative cross-couplings have been extensively developed as environmentally friendly and facile alternatives to the current cross-coupling methods. In Chapter 5 the attempted development of a decarboxylative cross-coupling reaction of cyclopropanes is described. Conclusions and future work are outlined in Chapter 6, followed by the experimental details in Chapter 7.

At the beginning of the nineteenth century, the medieval Florentine poet Dante Alighieri was an almost completely unknown figure in the United States. Yet, by mid-century, he was considered by many Americans to be one of the world's greatest poets and his major epic, the Divine Comedy, was translated during the Civil War by the most popular American poet at the time, Henry Wadsworth Longfellow. This dissertation examines Dante's nineteenth-century emergence in the United States and the historical and cultural reasons why Dante, for many nineteenth-century Americans, became a highly-regarded literary figure and an unexpectedly popular poet during the Civil War. Using new historicist and book studies methodologies, it argues that Dante was widely viewed as an important theological-political poet, a cultural representative of Italy and nineteenth-century Italian nationalism and liberalism, one who spoke powerfully to antebellum and wartime issues of national disunity, states' rights, the nature of empire, and the justice and injustice of civil war. American periodicals and English-language translations of the Comedy touted Dante as a great national poet--a model who might inspire any would-be national poet of the United States--while interpreting his biography and the Comedy in terms of American and transatlantic political events, ideologies, and discourses. Aware of such promotion, many American writers, including Longfellow, James Russell Lowell, Herman Melville, and Walt Whitman, read and interpreted the Comedy in terms of national politics and, by the early 1860s, the Civil War. Given its relevance and popularity during the 1860s--numerous books by or about Dante were published in the United States during this decade--the Divine Comedy thus became an important epic poem of the Civil War, a poem that Longfellow and Walt Whitman turned to while constructing their wartime and Reconstruction-era poetry.

Thesis (D. Min.)--Gordon-Conwell Theological Seminary, 1997. / Abstract and vita. Includes bibliographical references (leaves 216-225).

At the height of their popularity in the mid-nineteenth century, a vast transatlantic readership conferred on Longfellow and Tennyson the title "The People's Poet." This examination of Anglo-American Victorian poetry attempts to account for that phenomenon. A poetic work is first defined as an aesthetic experience that occurs within a triangular matrix of text, author, and reader. As reception theorist Hans Robert Jauss contends, both the creator's and the receptor's aesthetic experiences are filtered through a historically determined "horizon of expectations" that governs popular appeal. A historical account of the publication and promotion of Longfellow's and Tennyson's poetry provides empirical evidence for how and why their poetic texts appealed to a widespread readership. This account is followed by an analysis of the class and gender of Victorian readers of poetry that considers the role of "consumers" in the production of both poetry and poetic personae as commodities for public consumption. The development of each poet's voice is then examined in a context of a gendered "separate-sphere" ideology to explain how both Longfellow's and Tennyson's adoption of "feminine" cadences in their respective voices influenced the nineteenth-century reception of their work. The final two chapters analyze select texts—lyric and narrative—to determine reasons for their popular appeal in relation to the level of active reader engagement in the poetic experience. Through affective lyricism, as in Longfellow's "Psalm of Life" and Tennyson's "Break, break, break," these poets demanded that their readers listen; through sentiment transformed into domestic allegory, as in Miles Standish and Enoch Arden, these poets demanded further that they feel. While both Victorian poets were later decanonized by their modern successors, contemporary critics, mainly academic, have restored Tennyson to the literary canon while relegating Longfellow to a second-rate schoolroom status. The conclusion speculates on the possible reasons underlying the disparate reputations assigned to the two poets, both of whom, during their lifetimes, shared equally the fame and fortune that attended their role as "The People's Voice." / Arts, Faculty of / English, Department of / Graduate