Nos últimos anos a química é apontada como solução para diversos problemas globais originados por um modo de vida não sustentável, em virtude disso o desenvolvimento econômico e social ficam vinculados aos conhecimentos em ações sustentáveis embasadas na química verde. Neste contexto emerge a indústria química baseada em matérias-primas renováveis, dentre as biomassas renováveis destacam-se os carboidratos com cerca de 75% da biomassa da terra. Os glicosídeos são moléculas orgânicas nas quais o açúcar está ligado à uma porção não-carboidrato (aglicona), dentre eles os C-glicosídeos se destacam por apresentarem tanto resistência à hidrólise ácida quanto à enzimática, característica que confere interesse a indústria de fármacos e às ciências dos materiais apresentando-se como excelentes blocos de construção. A condensação de Knoevenagel é a reação entre um grupo metileno ativado e um aldeído ou cetona levando à formação de um composto β, β-insaturado e é muito relevante na derivatização de C-glicosídeos. O objetivo principal deste trabalho é empregar a D-glicose, como fonte de matéria-prima renovável, na obtenção de Cglicosídeos e potenciais derivados de interesse industrial, visando oferecer ao ambiente uma opção através de processos mais sustentáveis, para isso dividiu-se o trabalho em três etapas: a primeira de preparação da cetona β-C-glicosídeos e reações de proteções, a segunda, de derivações diretas dessas moléculas, por meio das preparações das oximas, das aril cetonas C-glicosídeos, da cicloexenona C-glicosídeo e do metil pentenol C-glicosídeo e a terceira consistiu de derivação de moléculas, obtidas na segunda etapa, em gem halo-nitro, oxima aril e isoxazol aril. Na primeira etapa, síntese da cetona β-C-glicosídeo, fez-se alterações metodológicas e obteve-se um rendimento médio de 92%, o composto foi confirmado por TGA, FT-IR e RMN 13C, nas reações de proteção à cetona β-C-glicosídeo, acetilação e benzoilação, obteve-se rendimentos de 60% e 31,4% respectivamente, os compostos foram confirmados por FT-IR e RMN 13C. Na segunda etapa sintetizou a aril cetona C-glicosídeo, desprotegida e protegida, com 91% e 78% de rendimentos respectivamente, a cicloexenona C-glicosídeo acetilada com 60% de rendimento e o metil pentenil C-glicosídeo acetilado com até 71% de rendimento, oximas a partir da cetona β-C-glicosídeo desprotegida e posterior proteção (economizando uma etapa) e oximas a partir da cetona β-C-glicosídeo acetilada obtendo rendimentos de 73,6 % e 83%, também foi sintetizada a oxima da glicose e sua acetilação gerou o nitrilo da glicose em 60% de rendimento, os compostos foram confirmados por FT-IR e RMN 13C. Na terceira etapa foram obtidos os derivados, gem bromo-nitro C-glicosídeo acetilado 30% (rota desprotegida) e 73% (rota protegida), gemcloro C-glicosídeo acetilados 30% (rota desprotegida) e 72% (rota protegida). A aril cetona C-glicosídeo acetilada, a oxima aril C-glicosídeo acetilada e isoxazol C-glicosídeo acetilado apresentaram rendimentos 45%, 78% e 31% respectivamente, todos confirmados por FT-IR e RMN 13C. A síntese da cetona β-C-glicosídeo desprotegida em meio aquoso alcalino apresenta um alto rendimento e demonstrou uma enorme versatilidade podendo ser empregada na obtenção de muitos derivados, no entanto as reações de proteção são necessárias para derivação dessas moléculas e facilitação da análise. / In recent years, chemistry has been identified as a solution to several global problems caused by an unsustainable way of life, as economic and social development are linked to the knowledge of sustainable actions based on green chemistry. In this context emerges the chemical industry based on renewable raw materials, among the renewable biomasses stand out the carbohydrates with about 75% of the earth\'s biomass. Glycosides are organic molecules in which sugar is bound to a non-carbohydrate (aglycone) moiety, among them the C-glycosides stand out because they have both resistance to acid and enzymatic hydrolysis, which is of interest to the pharmaceutical industry and sciences of materials presenting themselves as excellent building blocks. The Knoevenagel condensation is the reaction between an activated methylene group and an aldehyde or ketone leading to the formation of an β, β-unsaturated compound and is very relevant in the derivatization of Cglycosides. The main objective of this work is to use D-glucose, as a source of renewable raw material, to obtain C-glycosides and potential derivatives of industrial interest, aiming to offer the environment an option employing more sustainable processes, for this the work was divided in three stages: the first one of preparation of the ketone β-C-glycosides and reactions of protections, the second, of direct derivations of these molecules, through the preparations of oximes, aryl ketones C-glycosides, cyclohexenone C-glycoside and methyl pentenol C-glycoside and the third step consisted of derivation of molecules obtained in the second step in gem halo-nitro, aryl oxime and isoxazole aryl. In the first step, synthesis of the β-C-glycoside ketone made methodological changes and obtained an average yield of 92%, the compound was confirmed by TGA, FT-IR and 13C NMR, in the protection reactions to β-C-glycoside ketone, acetylation and benzoylation, yields of 60% and 31.4% respectively were obtained, the compounds were confirmed by FT-IR and 13C NMR. In the second step, the unprotected and protected C-glycoside aryl ketone was synthesized in 91% and 78% yields respectively, the acetylated C-glycoside cyclohexenone in 60% yield and the acetylated methyl pentenyl C-glycoside in up to 71% yield, oximes from the deprotected β-C-glycoside ketone and subsequent protection (saving one step) and oximes from acetylated β-C-glucoside ketone yielding 73.6% and 83% yields, the glucose oxime was also synthesized and its acetylation generated the glucose nitrile in 60% yield, the compounds were confirmed by FT-IR and 13 C NMR. In the third stage the derivatives were obtained, gem bromo-nitro C-glycoside acetylated 30% (unprotected route) and 73% (protected route), gem-chloro C-glycoside acetylated 30% (route deprotected) and 72% (protected route). The acetylated C-glycoside aryl ketone, the acetylated C-glycoside aryl oxime and the acetylated C-glycoside isoxazole presented yields of 45%, 78% and 31% respectively, all confirmed by FT-IR and 13C NMR. The synthesis of β-C-glycoside ketone deprotected in alkaline aqueous medium presents a high yield and demonstrated an enormous versatility that can be used to obtain many derivatives, however the protection reactions are necessary for derivation of this molecules and facilitation of the analysis.

Steroids are important biological regulators existing in hormones which are used to control metabolism of the body. There are widespread applications in the pharmaceutical industry. Drugs of steroid nature - anti-inflammatory and antiallergic corticosteroids, diuretics, anabolics, androgens, gestagens, contraceptives, antitumor medications, etc. - are now widely used in human and veterinary medicine. Nowadays, biotechnological modifications of steroids are preferred over chemical modifications as a green chemistry since they are more likely to be natural. In this work four different Fusarium species were screened for bioconversion of steroids into pharmaceutically important derivatives of steroids by reduction, dehydrogenation, side-chain degradation etc. on A and D-rings containing many active sites. Fusarium spp. used in this work, namely Fusarium roseum OUT 4019, Fusarium anguioides OUT 4017, Fusarium bulbigenum OUT 4115 and Fusarium solani OUT 4021 are filamentous fungi, which belong to the class of Deuteromyces. They can grow using simple carbohydrates and nitrogen sources. 4-androstene-3,17-dione conversion is used as a model system. Under same environmental conditions it is found that whole cells of Fusarium roseum OUT 4019 can dehydrogenate at C-1 and C-2 producing androsta-1,4-diene-3,17-dione and also reduce at C-17 in addition to dehydrogenate at C-1 and C-2 producing 17-hydroxyandrosta- 1,4-dien-3-one, Fusarium anguioides OUT 4017 can reduce at C-17 producing 17-hydroxy-androst-4-en-3-one, Fusarium solani OUT 4021 can reduce at C-3 and C-17 producing androst-4-ene-3,17-diol at 25 C&deg / and 160 rpm with uncontrolled pH. In these conversions, androsta-1,4-diene-3,17-dione, 17-hydroxy-androsta-1,4-dien- 3-one, 17-hydroxy-androst-4-en-3-one, androst-4-ene-3,17-diol were isolated with 54 %, 22 %, 26 %, 90 % yields, respectively. In another study, bioconversion reactions of aromatic methyl ethers by Fusarium roseum OUT 4019 were investigated and for some compounds, cleavage of methyl ether was observed.

The objective of this presented study was to synthesize optically active compounds considered to be key intermediates in the synthesis of Oseltamivir (Tamiflu) by performing chemical and biotechnological methods. Thereof, the carboethoxy cyclohexenone skeleton first was synthesized utilizing easily available substances. The synthesis of alpha-hydroxy ketones in enantiomerically pure form offers a great importance in the synthesis of biologically active compounds. Toward this fact, the enantioselective synthesis of alpha-hydroxy carboethoxy cyclohexenone scaffold has been accomplished by following the routes which were manganese(III) acetate-mediated chemical oxidation followed by enzyme-mediated hydrolysis and additionally microbial direct biooxidation by whole cells of fungi expressly A. oryzae and A. flavus. A very satisfying results have been obtained by both of the methods.

This thesis focuses on the asymmetric reduction of N-protected derivatives of (3S)-3-amino-1-chloro-4-phenyl-2-butanone to their corresponding diastereomeric alcohol products, which are key intermediates in the synthesis of HIV protease inhibitors. Although the stereoselective synthesis of the (S,S) alcohol product is easily achieved, preparing the (R,S) diastereomer is much more challenging. I investigated three diastereoselective reduction processes: 1) Meerwein-Ponndorf-Verley (MPV) reduction, 2) asymmetric transfer hydrogenation, and 3) boron reducing agents. The diastereoselectivity of the MPV reduction still favored the (S,S) product; however, I discovered a significant rate enhancement when the standard catalyst (aluminum isopropoxide) was replaced with aluminum tert-butoxide. Many reaction variables were investigated in the asymmetric transfer hydrogenation reaction and the diastereoselectivity was improved to give a ratio of the desired (R,S) diastereomer to the undesired (S,S) alcohol of 9.5:1. Using chiral oxazaborolidine catalysts, an unprecedented (R,S) to (S,S) ratio of 9.5:1 was achieved. Finally, I investigated the effect of the N-protecting group on the stereoselectivity of the reduction. When the original boc-protecting group was replaced with a phthalimide group, the diastereoselectivity of the MPV reduction was reversed to favor the desired (R,S) product.

Thesis (Ph. D.)--University of Oklahoma. / Bibliography: leaves 147-164.

The work described in this thesis is focused on the development of new bidentate iridium complexes and their applications in the asymmetric reduction of olefins, ketones and imines. Three new types of iridium complexes were synthesized, which included pyridine derived chiral N,P-iridium complexes, achiral NHC complexes and chiral NHC-phosphine complexes. A study of their catalytic applications demonstrated a high efficiency of the N,P-iridium complexes for asymmetric hydrogenation of olefins, with good enantioselectivity. The carbene complexes were found to be very efficient hydrogen transfer mediators capable of abstracting hydrogen from alcohols and subsequently transfer it to other unsaturated bonds. This hydrogen transferring property of the carbene complexes was used in the development of C–C and C–N bond formation reactions via the hydrogen borrowing process. The complexes displayed high catalytic reactivity using 0.5–1.0 mol% of the catalyst and mild reaction conditions. Finally chiral carbene complexes were found to be activated by hydrogen gas. Their corresponding iridium hydride species were able to reduce ketones and imines with high efficiency and enantioselectivity without any additives, base or acid. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 5: Submitted. Paper 6: Manuscript.</p><p> </p>

A facile method for the direct conversion of oximes into carbonyl compounds by treatment with manganese triacetate is described. Manganese triacetate can be used for an effective and mild oxidizing agent for the regeneration of carbonyl compounds in good yield. Many functional groups are tolerated under reaction conditions.

Universiẗat, Diss., 2005--Bielefeld. / Erscheinungsjahr an der Haupttitelstelle: 2004.

Techn. Universiẗat, Diss., 2005--Dresden.

Submitted by Carlos Augusto Rolim da Silva Junior (carlos_jrolim@hotmail.com) on 2015-11-19T15:51:43Z No. of bitstreams: 1 arquivototal.pdf: 2129832 bytes, checksum: 3b684f127d50c659a84b4938455dd401 (MD5) / Made available in DSpace on 2015-11-19T15:51:43Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 2129832 bytes, checksum: 3b684f127d50c659a84b4938455dd401 (MD5) Previous issue date: 2013-08-14 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Variations in the Body Condition Index (BCI), glycemia and ketonemia of Artibeus planirostris (Chiroptera: Phyllostomidae) were analyzed in Tabuleiro and Atlantic Forest areas of Paraíba State, at field and captivity conditions. BCI was chosen based on the minimum influence of forearm length on body mass and evaluated according to sex, reproductive status, location and time of capture. Glycemia and ketonemia were also correlated with BCI and other variables. Variations in the BCI and glycemia were recorded after capture, fasting and feeding bats in captivity. The results showed that Le Cren’s Relative Condition Factor (Kn) and Simple Ratio with Curve Fitting (CFt) indices were the most suitable for A. planirostris. Blood glucose was correlated with Kn and proved to be a good method to validate the BCI. In Guaribas Biological Reserve, females had higher Kn, probably related to biases in the methodology or energy reserves during reproductive status. Tabuleiro’s bats had higher Kn and glucose levels than those in Atlantic Forest, which may indicate sub-sampling by the exclusion of bats in the canopy of the latter area. The twelve hours of collection indicated that A. planirostris forages throughout the night and presents a variation of Kn and glucose, especially during early morning, when it reaches the maximum levels before it returns to the shelter. In captivity, bats showed a great variation of Kn and glucose levels after fasting and feeding, recording Kn measures for these states that can be used as a parameter for field studies in the region. Blood glucose remained at normal values for mammals, but about 30% of the bats had levels higher than normal during capture in all areas, probably due to stress. Ketone bodies have been correlated only to glucose, and thus were not considered a good method to validate Kn in these animals. / As variações no Índice de Condição Corporal (ICC), glicemia e cetonemia de Artibeus planirostris (Chiroptera: Phyllostomidae) foram analisadas em áreas de Tabuleiro e Mata Atlântica da Paraíba em campo e cativeiro. O ICC escolhido foi baseado na menor influência do comprimento do antebraço na massa corporal e avaliado de acordo com o sexo, estado reprodutivo, local e horário de coleta. A glicemia e cetonemia também foram correlacionadas entre si, com o ICC e as demais variáveis, e variações no ICC e glicemia foram registradas após captura, jejum e alimentação de morcegos em cativeiro. Os resultados mostraram que o Fator de Condição Relativa de Le Cren (Kn) e a Razão Simples com Ajuste de Curva (AjC) foram os índices mais indicados para A. planirostris. A glicemia esteve correlacionada com o Kn e se mostrou um bom método para validar o ICC utilizado. Na REBIO Guaribas, as fêmeas tiveram maior Kn, provavelmente relacionado a vieses na metodologia ou a reservas energéticas durante o estado reprodutivo. Os morcegos do Tabuleiro obtiveram maior Kn e glicemia que os da Mata Atlântica, o que pode indicar subamostragem pela exclusão de morcegos que forrageavam no dossel da última área. As doze horas de coleta indicaram que A. planirostris forrageia durante toda a noite com variação de Kn e glicemia, sobretudo durante a madrugada, quando atinge o valor máximo antes de retornar para o abrigo. Em cativeiro, os morcegos apresentaram grande variação de Kn e glicemia em jejum e após a alimentação, registrando medidas de Kn para estes estados que podem ser utilizadas como parâmetro para estudos em campo na região. A glicemia manteve valores considerados normais para mamíferos, mas cerca de 30% dos morcegos apresentaram níveis acima do normal após a captura em todas as áreas, provavelmente devido ao estresse. Os corpos de cetona estiveram correlacionados apenas aos níveis de glicose e, portanto, não foi considerado um bom método para validar o Kn nestes animais.