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The possible role of the prostaglandins (PGs) in the regulation of protein turnover was investigated, firstly in hypertrophying rat skeletal muscle at 20 hours, 3 days and 7 days after synergist tenotomy, and secondly, in various tissues of the rainbow trout (Salmo gairdneri, Richardson) following re-feeding. An inhibitor of PG synthesis was used in both cases (fenbufen and indomethacin, respectively). 1) Fenbufen (at a dose of 1200mg/kg of diet) did not inhibit the hypertrophy of the soleus and plantaris muscles although there appeared to be an initial reduction in muscle RNA content. 2) Muscle growth was generally increased in fenbufen fed rats by 7 days after synergist tenotomy (10 days on fenbufen diet). 3) The fractional rate of protein synthesis in both control and overloaded muscles was reduced by fenbufen at this time (in 86g rats). The calculated rates of protein breakdown were also reduced in these muscles but to a greater extent than synthesis. This inhibition of protein degradation was most marked in the overloaded soleus and plantaris muscles. 4) The tenotomised gastrocnemius muscle experienced a true atrophy in the fenbufen-treated rats by 7 days. This atrophy involved greatly elevated rates of protein degradation when compared to the tenotomised muscle from rats fed a normal diet. In 6 day fasted rainbow trout, tissue protein synthesis was measured at 3 hours, 6 hours and 12 hours after re-feeding. The rapidity of the stimulation of protein synthesis by re-feeding and the nature of the response was tissue-specific. The administration of indomethacin (at a dose of 2mg/100g body weight) one hour prior to the meal, partially blocked the re-feeding response of protein synthesis in the gill at 6 hours after the meal, but stimulated protein synthesis in the liver and white muscle at this time.

A síntese do análogo de prostaglandina, n-heptil-4-(3-hidroxi-trans-1-octenil)-1,3-tiazolidina-2-tiona, foi realizada através das seguintes etapas: obtenção do anel ciclopentânico, N-alquilação do 4-(R)-etoxicarbonil-1,3-tiazolidina-2-tiona, obtenção do álcool do composto derivado N-alquilado, oxidação do álcool ao aldeído correspondente, introdução da cadeia-ω no anel ciclopentânico do análogo da prostaglandina e finalmente, a redução da enona ao álcool alílico correspondente. O produto final foi obtido sob a forma de uma mistura diastereoisomérica. A cisteína, utilizada como reagente de partida, é responsável pela formação do anel ciclopentânico da prostaglandina (intermediário chave da reação). Na etapa de introdução da cadeia-α à prostaglandina, por meio de uma N-Alquilação, foi necessário introduzir uma reação de redução do éster a álcool e posteriormente uma proteção do álcool, evitando assim possíveis competições CxN e OxN- Alquilação respectivamente. Após remoção do grupo protetor do álcool, este foi oxidado ao aldeído correspondente, empregando diferentes agentes oxidantes. Entre estes, o reagente de Swern foi escolhido para o trabalho, por que apresentou maior seletividade. A introdução da cadeia-ω no anel de cinco membros do análogo da prostaglandina, foi realizada via uma reação de Horner-Wadsworth-Emmons, utilizando-se uma fosforana estabilizada, para garantir a configuração E na dubla ligação formada no C13 - C14, geralmente encontrada nas prostaglandinas naturais. A prostaglandina obtida por esta rota será testada como agente broncodilatador ou inibidor de agregação plaquetária, no Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBIO) / The synthesis of the prostaglandin analog, n-heptyl-4-(3-hydroxy-trans-1-octenyl)-1,3-thiazolidin-2-thione, was carried through the following steps: cyclopentane ring obtainment; N-alkylation of 4-(R)-ethoxycarbonyl-1,3-thiazolidin-2-tione; obtainment of the alcohol from the N-alkyl derivative compound; oxidation of the alcohol to the corresponding aldehyde; introduction of the ω-chain in the : cyclopentane ring of the prostaglandin analog; and finally, the reduction of the enone to the corresponding allyl alcohol. The final product was obtained as a distereomeric mixture. The cystein utilized as starting material; is responsible for the prostaglandin cyclopentane ring formation (the reaction key intermediate). The step of introduction the ω-chain in the cyclopentanone ring, by means of an N-alkylation, it was needed to reduce an intermediate esther, and the formed alcohol was further protected conveniently, thus avoiding possible CxN- and OxN-alkylation competition reactions, respectively. Afther removal of the protecting group from the alcohol, it was oxidized to the corresponding aldehyde employing different oxidizing agents. Among these, the Swern reagent was chosen for the work, because of its greater selectivity. The introduction of the ω-chain into the five membered ring of the prostaglandin analog was performed via a Horner-Wadsworth-Emmons reactions, using a stabilized phosphorane in order to guarantee the E configuration of the double bond formed on C13 - C14, commonly found in natural prostaglandins. The prostaglandins obtained in this way will have its possible biological activities assayed as bronchodilatory or platelet aggregations inhibition agent in the Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBIO).

A síntese do análogo de prostaglandina, n-heptil-4-(3-hidroxi-trans-1-octenil)-1,3-tiazolidina-2-tiona, foi realizada através das seguintes etapas: obtenção do anel ciclopentânico, N-alquilação do 4-(R)-etoxicarbonil-1,3-tiazolidina-2-tiona, obtenção do álcool do composto derivado N-alquilado, oxidação do álcool ao aldeído correspondente, introdução da cadeia-ω no anel ciclopentânico do análogo da prostaglandina e finalmente, a redução da enona ao álcool alílico correspondente. O produto final foi obtido sob a forma de uma mistura diastereoisomérica. A cisteína, utilizada como reagente de partida, é responsável pela formação do anel ciclopentânico da prostaglandina (intermediário chave da reação). Na etapa de introdução da cadeia-α à prostaglandina, por meio de uma N-Alquilação, foi necessário introduzir uma reação de redução do éster a álcool e posteriormente uma proteção do álcool, evitando assim possíveis competições CxN e OxN- Alquilação respectivamente. Após remoção do grupo protetor do álcool, este foi oxidado ao aldeído correspondente, empregando diferentes agentes oxidantes. Entre estes, o reagente de Swern foi escolhido para o trabalho, por que apresentou maior seletividade. A introdução da cadeia-ω no anel de cinco membros do análogo da prostaglandina, foi realizada via uma reação de Horner-Wadsworth-Emmons, utilizando-se uma fosforana estabilizada, para garantir a configuração E na dubla ligação formada no C13 - C14, geralmente encontrada nas prostaglandinas naturais. A prostaglandina obtida por esta rota será testada como agente broncodilatador ou inibidor de agregação plaquetária, no Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBIO) / The synthesis of the prostaglandin analog, n-heptyl-4-(3-hydroxy-trans-1-octenyl)-1,3-thiazolidin-2-thione, was carried through the following steps: cyclopentane ring obtainment; N-alkylation of 4-(R)-ethoxycarbonyl-1,3-thiazolidin-2-tione; obtainment of the alcohol from the N-alkyl derivative compound; oxidation of the alcohol to the corresponding aldehyde; introduction of the ω-chain in the : cyclopentane ring of the prostaglandin analog; and finally, the reduction of the enone to the corresponding allyl alcohol. The final product was obtained as a distereomeric mixture. The cystein utilized as starting material; is responsible for the prostaglandin cyclopentane ring formation (the reaction key intermediate). The step of introduction the ω-chain in the cyclopentanone ring, by means of an N-alkylation, it was needed to reduce an intermediate esther, and the formed alcohol was further protected conveniently, thus avoiding possible CxN- and OxN-alkylation competition reactions, respectively. Afther removal of the protecting group from the alcohol, it was oxidized to the corresponding aldehyde employing different oxidizing agents. Among these, the Swern reagent was chosen for the work, because of its greater selectivity. The introduction of the ω-chain into the five membered ring of the prostaglandin analog was performed via a Horner-Wadsworth-Emmons reactions, using a stabilized phosphorane in order to guarantee the E configuration of the double bond formed on C13 - C14, commonly found in natural prostaglandins. The prostaglandins obtained in this way will have its possible biological activities assayed as bronchodilatory or platelet aggregations inhibition agent in the Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBIO).

<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>