Chiral cyclic polyoxo-ketones are important structural units in many natural products, biologically active compouds, such as prostaglandins, didemnenones, sarkomycin, punaglandin, clavulone, etc. In this work, a chemoenzymatic synthesis of both enantiomers of the &amp / #945 / &rsquo / -acetoxy-&amp / #945 / -methyl and &amp / #947 / -hydroxy-&amp / #945 / -methyl cyclic enones starting from &amp / #945 / -methyl-&amp / #946 / -methoxy cyclic enone is described. Manganese (III) acetate-mediated acetoxylation followed by the enzyme-mediated hydrolysis of &amp / #945 / &rsquo / -acetoxy enone provides acetoxy enones. The reduction of the hydroxy enone, obtained from hydrolysis, furnished both enantiomers of 4-hydroxy enone or &amp / #947 / -hydroxy enone by using LiAlH4. This study is a model for the synthesis of these type compounds

Thesis (Ph.D. in Cell and Developmental Biology) -- University of Colorado at Denver and Health Sciences Center, 2005. / Typescript. Includes bibliographical references (leaves 123-141). Free to UCDHSC affiliates. Online version available via ProQuest Digital Dissertations;

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Made available in DSpace on 2015-07-22T20:50:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-02-27. Added 1 bitstream(s) on 2015-08-11T03:25:51Z : No. of bitstreams: 1 Publico-10940a.pdf: 1658831 bytes, checksum: ef7d2834f9c77439f22a6b2da7c722c7 (MD5). Added 1 bitstream(s) on 2015-08-11T03:25:52Z : No. of bitstreams: 2 Publico-10940a.pdf: 1658831 bytes, checksum: ef7d2834f9c77439f22a6b2da7c722c7 (MD5) Publico-10940b.pdf: 1216468 bytes, checksum: bd1ea49c2bfdfa8789e58924c9513820 (MD5) / Nesta dissertação, são descritos os estudos visando a síntese total da isodolastatina H, um éster peptídico natural da família das dolastatinas com grande atividade citotóxica. O diferencial nesta sintese sobre as outras, foi a construcao das unidades gama-aminoacidos Dil e Dap, que foram obtidas via reacao de adicao de sais de crotil e aliltrifluoroboratos a L -prolinal e L -valinal, respectivamente. Os fragmentos foram posteriormente unidos por reacoes de esterificacao e amidacao. / This dissertation, are described the study towards to total synthesis of isodolastatin H, a natural peptide ester of dolastatin family with great citotoxicity activity. The main focus in this synthesis, is the construction of gama-aminoacid units Dil and Dap, obtained via addition reaction of crotyl and allyltrifluoroborate salts with L -prolinal and L-valinal, respectively. The junction of fragments was subsequently made from esterification and amidation reaction. / TEDE / BV UNIFESP: Teses e dissertações

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Submitted by Marco Antonio Oliveira da Silva (maosilva@ipen.br) on 2016-08-26T11:30:14Z No. of bitstreams: 0 / Made available in DSpace on 2016-08-26T11:30:14Z (GMT). No. of bitstreams: 0 / Diversos estudos de serpentes têm mostrado que algumas substâncias componentes de seus venenos possuem eficiência na atividade antitumoral nos ensaios realizados em laboratório em células in vitro e in vivo. O veneno da cascavel Crotalus vegrandis possuem atividades neurotoxica, miotoxica e hemorrágica. A crotoxina simile é um importante componente desse veneno sendo formada por uma proteína que possui uma unidade ácida (Crotapotina) ligada a uma subunidade básica (PLA2). Devido ao fato de existirem poucos estudos relativos ao veneno de Crotalus vegrandis, torna-se necessário o isolamento e a caracterização de suas biomoléculas e uma maior investigação do seu potencial e sua eficácia como agente terapêutico contra células tumorais. No presente trabalho, foi realizado o isolamento e a caracterização da crotoxina simile de Crotalus vegrandis, bem como seu efeito citotóxico em células L929 e B16F10. Realizou-se o cultivo dessas células em placas com 96 poços, para, então, serem colocadas em contato direto com diferentes frações do veneno purificado de Crotalus vegrandis por um tempo total de 48 horas. Para efeitos de comparação realizou-se o mesmo ensaio com frações do veneno purificado da cascavel brasileira Crotalus durissus terrificus. Para a avaliação da viabilidade celular o tratamento com as frações do veneno purificado de Crotalus vegrandis e Crotalus durissus terrificus, realizou-se os ensaios com MTT. Os resultados mostraram uma atividade de grande toxicidade para ambos os venenos em células tumorais B16F10 e pouca toxicidade para as células normais L929. Ainda nos ensaios comparativos com os dois venenos, verificou-se que, para uma dada concentração, as frações do veneno de Crotalus vegrandis possuem uma maior eficiência que qualquer concentração do veneno de Crotalus durissus terrificus, havendo uma maior especificidade para as células B16F10. A crotoxina símile isolada do veneno de Crotalus vegrandis apresentou atividade citotóxica mais preponderante na linhagem celular tumoral B16F10, após 48 horas concentrações de 250 e 125 ug/mL. / Dissertação (Mestrado em Tecnologia Nuclear) / IPEN/D / Instituto de Pesquisas Energéticas e Nucleares - IPEN-CNEN/SP

Durante a fase de crescimento e terminação, 1890 frangos de corte machos da linhagem Cobb®500 foram submetidos a altas temperaturas e alimentados com dietas experimentais contendo três fontes de metionina (DL-Met, DL-HMTBA e DL-Met/ DL-HMTBA), três níveis de vitamina E (15 UI, 45 UI e 100 UI) e duas relações Arg:Lis (0,9 e 1,5), cujo delineamento fatorial 3 x 3 x 2 totalizou 18 tratamentos, com sete repetições de 15 aves cada. Ao final do período experimental, os parâmetros de desempenho zootécnico como consumo de ração, peso corporal, conversão alimentar e rendimento de carcaça, peito e pernas foram avaliados e, após análise estatística, comprovou-se que não houve interação entre os fatores. Dessa maneira, os efeitos individuais dos elementos testados foram analisados e observou-se que a utilização de diferentes fontes de metionina e a inclusão de vitamina E nas quantidades testadas não apresentaram diferenças significativas. Porém, a maior inclusão de arginina na dieta proporcionou melhora nos resultados de ganho de peso, peso corporal e conversão alimentar, mas não resultou em diferenças significativas nos parâmetros de carcaça avaliados. / During the growing and the finishing, 1890 male broiler chickens of Cobb 500 ® were subjected to high temperatures and fed with experimental diets containing three sources of methionine (DL -Met ,DL - HMTBA and DL-Met/DL - HMTBA), three levels of vitamin E (15 IU, 45 IU and 100 IU) and two relations Arg:Lys (0.9 and 1.5), whose factorial design 3 x 3 x 2 totaled 18 treatments with seven replicates of 15 birds each. At the end of the experimental period, the growth performance parameters such as feed intake, body weight, feed conversion and carcass, breast and legs yieldwere evaluated and, after statistical analysis, it was shown that there was no interaction between factors. Thus, the effects of the tested individual elements were analyzed and it was found that the use of different sources of methionine and the inclusion of vitamin E in the amounts tested showed no significant differences. However, the increased inclusion of arginine in the diet improved results in weight gain, body weight and feed conversion, but resulted in no significant differences in carcass parameters.

Esta dissertação apresenta um estudo sobre a contração de anel de ésteres ß,y-insaturados promovida por trinitrato de tálio (TTN) e de 1,2-di-hidronaftalenos promovida por hidroxi(tosiloxi)iodobenzeno (HTIB), também conhecido como reagente de Koser. Ambos estudos visaram à síntese de indanos funcionalizados. A reação de uma série de ésteres ß,y-insaturados (por exemplo 2-(3,4-di-hidronaftalen-1-il)-proprionato de etila) com TTN em ácido acético forneceu os correspondentes produtos de contração, formando indanos em bons rendimentos. A presença de grupos doadores de elétrons na posição 6 no anel aromático resultou no aumento do rendimento do produto de contração, enquanto que grupos atraentes de elétrons na posição 7 do anel aromático acarretou o decréscimo do rendimento do indano quando comparado a substratos que não são substituídos nesta posição. O aumento da cadeia alquílica na posição alfa-carbonila não interferiu no rendimento do produto desejado. O éster substituído por uma metila na posição 4 do anel ciclo-hexênico levou preferencialmente ao indano trans-1,3-dissubstituído. A reação do 1,2-di-hidronaftaleno com HTIB em metanol levou ao produto de contração de anel 1-dimetoximetil-indano com rendimento moderado, além dos produtos de adição cis e trans-1,2-dimetoxi-1,2,3,4-tetra-hidronaftaleno. No entanto, a reação desse substrato com HTIB em acetonitrila, diclorometano ou trimetil-ortoformiato forneceu o produto de aromatização (naftaleno). Contudo, os produtos de contração, 1-indano-1-il-etanona e 1-(3-metil-indan-1-il)-etanona foram formados em bons rendimentos quando o 4-metil-1,2-di-hidronaftaleno e o 1,4-dimetil-1,2-di-hidronaftaleno, respectivamente, foram tratados com HTIB em acetonitrila. No caso do 1,4-dimetil-1,2-di-hidronaftaleno há uma predominância na formação do isômero trans. Finalmente, para a reação de 4-metil-1,2-di-hidronaftaleno com HTIB em metanol foram formados os produtos de adição (cis e trans-1,2-dimetoxi-1,2,3,4-tetrahidro-1-metil-naftaleno) em ótimos rendimentos. / This dissertation presents a study about the ring contraction of ß,y-unsaturated esters promoted by thallium trinitrate (TTN) and 1,2-dihydronaphthalenes promoted by hydroxy(tosyloxy)iodobenzene (HTIB). Both studies aimed the synthesis of functionalizated indans. The reaction of a series of ß,y-unsaturad esters with TTN in acetic acid led to the corresponding ring contraction products, giving indans in good yields. The presence of electron donating groups in the 6-position of the aromatic ring increases the yield of the ring contraction product. On the other hand, electron withdrawing groups in the 7-position of the aromatic ring leds to a decrease of the yield of the desired product, when compared to substrates which are not substituted in this position. The increasement of the alkane chain at the alpha-carbonyl position did not interfere in the yield of the ring contraction product. The esters substituted by an alkyl group at 4-position of the ciclohexene ring leads to the ring contraction product, where the trans-1,3-disubstituted indan is the major product. The reaction of 1,2-dihydronaphthalene with HTIB in methanol gave the ring contraction product 1-dimetoxymethyl-indan with moderate yield, together with the addition products cis- and trans-1,2-dimetoxy-1,2,3,4-tetrahydronaphthalene. On the other hand, the reaction of 1,2-dihydronaphthalene with HTIB in acetonitrile, dichloro-methane or trimethyl orthoformate gave the aromatization product (naphthalene). The reaction of 4-methyl-1,2-dihydronaphthalene and 1,4-dimethyl-1,2-dihydronaphthalene with HTIB in acetonitrile leads to ring contraction products 1-indan-1-yl-ethanone and 1-(trans-3-methyl-indan-1-yl)-ethanone, respectively, in good yieds. The reaction of 4-methyl-1,2-dihydronaphthalene with HTIB in methanol gave the addition products cis- and trans-1,2-dimetoxy-1,2,3,4-tetrahydro-1-methyl-naphthalene) with very good yield.

M.Tech. / There are over 250 cinnamon species existing worldwide, and amongst them, 2 species Cinnamomum cassia and Cinnamomum zeylanicum, are commonly used all over the world as spices, fragrances in perfumes and as medicines. These two species are distinguished from each other by the presence and absence of certain compounds depending on the origin and distribution of the plant. Nevertheless, all cinnamon species contain essential oils and water soluble components and the composition of these components found in each species depends on the type of species involved. These components are made up of phenyl propanoids, terpenes, flavonoids and saponins. In general, the essential oil component contains the following compounds: cinnamaldehyde as a major constituent with its derivatives cinnamic acid, cinnamyl alcohol, ethyl cinnamate, cinnamyl acetate and 2-methoxy cinnamaldehyde; eugenol; linalool; coumarin; carvone; carvacrol and β-caryophyllene. Most of these compounds are abundantly found in the bark except in the case of eugenol which is found in either leaves or bark depending on the species involved. The other water soluble component is composed of a group of compounds such as tannin, chalcone, catechins and anthocyanidins. These compounds polymerize to form methyl hydroxy chalcone polymers (MHCP) which has been shown to play an important role in lowering blood sugar levels in Type ll diabetic individuals. It is said that MHCP has an ability to promote the phosphorylation process which in turn activates the beta-cells and thereby creating insulin activity that will then convert glucose into glycogen. Besides all health benefits of cinnamon, the plant contains a toxic compound, coumarin which impacts badly on animals resulting in death, and little information on its toxicity to human beings has been documented. Concerns arose about the possible presence of coumarin in these formulations, since these formulations are made from the cinnamon and the plant contains coumarin. This work has investigated the potential toxicity of coumarin from cinnamon powder and cinnamon formulation. The components from both cinnamon samples were extracted using various solvents according to their polarities and these compounds were screened on thin layer chromatography (TLC). The essential oil components were separated by column chromatography, and quantified by using high performance liquid chromatography (HPLC), all components (essential oil and water soluble) were identified by HPLC, and finally the characterization of the essential oil components was done with infrared (IR) and nuclear magnetic resonance (NMR) whereas those of the water soluble were characterized by using liquid chromatography coupled to a mass spectrometer (LC-MS).

Polycyclic polyprenylated acylphloroglucinols (PPAPs) are plant- (Guttiferae) derived natural products. They have fascinating bicyclo[3.3.1]nonane-2,4,9-trione or [3.2.1]nonane-2,4,8-trione cores decorated with prenyl or geranyl groups. More than 200 PPAPs have been isolated, but only a few of them have been synthesized, although most of the synthesized PPAPs are of type A and have an exo substituent at C (7). Here, we are trying to make a type B 7-endo PPAP, 7-epi-clusianone. The synthetic plan involves an alkynylation–aldol strategy to construct the bicyclic core. Having established the bicyclic core, the synthesis presents a new challenge: the oxidation of a very hindered 2-alkenone to the β-hydroxy 2-alkenone.