Academic literature on the topic 'Crinane'

Boophone disticha is widely used in South African traditional medicine. Several of its biological properties can be corroborated via its alkaloid constituents. Previous research on this plant led to the isolation of several alkaloids, mainly of the crinane alkaloid group of the Amaryllidaceae. In the present study, one new compound 1- O-acetylbuphanamine (1) and four known crinane alkaloids were isolated chromatographically from the ethanol extract of the bulbs of B. disticha. Their structures were determined via spectroscopic methods, including 1D and 2D NMR, ESI-MS, HRMS and IR data.

A unified approach to the Amaryllidaceae alkaloids having a cis-3a-aryloctahydroindole scaffold is developed via a key Eschenmoser–Claisen rearrangement of all-carbon quaternary stereocenters present in these alkaloids. Utilizing this strategy, a concise total synthesis of (±)-mesembrane and (±)-crinane is achieved.

In the alkaloid galanthamine, the plant family Amaryllidaceae has endowed the pharmaceutical community with a potent and selective inhibitor of the enzyme acetylcholinestersae (AChE), of prominence in the chemotherapeutic approach towards motor neuron diseases. Following on the commercial success of this prescription drug in the treatment of Alzheimer's disease, it is anticipated that other drug candidates will in future emerge from the family. In this regard, the phenanthridones, exemplified by narciclasine and pancratistatin, of the lycorine series of Amaryllidaceae alkaloids have shown much promise as remarkably potent and selective anticancer agents, with a drug target of the series destined for the clinical market within the next decade. Given these interesting biological properties and their natural abundance, plants of the Amaryllidaceae have provided a diverse and accessible platform for phytochemical-based drug discovery. The crinane series of Amaryllidaceae alkaloids are also enriched with a significant array of biological properties. As a consequence of their close structural similarity to the anticancer agents of the lycorine series, the cytotoxic potential of crinane alkaloids has been realized through structure-activity relationship (SAR) studies involving targets of both semi-synthetic and natural origin, which has identified several members as leads with promising antiproliferative profiles. As the first of its kind, this review seeks to collate such information from the past few decades in advancing the crinane group as a viable platform for anticancer drug discovery.

In the alkaloid galanthamine, the plant family Amaryllidaceae has endowed the pharmaceutical community with a potent and selective inhibitor of the enzyme acetylcholinestersae (AChE), of prominence in the chemotherapeutic approach towards motor neuron diseases. Following on the commercial success of this prescription drug in the treatment of Alzheimer's disease, it is anticipated that other drug candidates will in future emerge from the family. In this regard, the phenanthridones, exemplified by narciclasine and pancratistatin, of the lycorine series of Amaryllidaceae alkaloids have shown much promise as remarkably potent and selective anticancer agents, with a drug target of the series destined for the clinical market within the next decade. Given these interesting biological properties and their natural abundance, plants of the Amaryllidaceae have provided a diverse and accessible platform for phytochemical-based drug discovery. The crinane series of Amaryllidaceae alkaloids are also enriched with a significant array of biological properties. As a consequence of their close structural similarity to the anticancer agents of the lycorine series, the cytotoxic potential of crinane alkaloids has been realized through structure-activity relationship (SAR) studies involving targets of both semi-synthetic and natural origin, which has identified several members as leads with promising antiproliferative profiles. As the first of its kind, this review seeks to collate such information from the past few decades in advancing the crinane group as a viable platform for anticancer drug discovery.

ABSTRACT. A series of crinane-type alkaloid ambelline derivatives were assessed for their potency to inhibit both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), which has been shown to be effective medicine for the treatment of Alzheimer’s disease. However, no enzyme modification has been reported total synthesis. In this work, two possible theoretical synthesis paths of Crinane-type alkaloid ambelline were discussed in this article. The major difficulty of the proposed synthesis was the synthesis of the quaternary carbon. One of the approaches emphasized on the reactions between cyclic and heterocyclic compounds and substrates on the intermediates to generate the quaternary carbon shown on the desired product. The other approach utilized series of amine reactions and Michael addition to create the precursor for the reactant in the Diels-Alder reaction and, therefore, the quaternary carbon, and finally, the desired natural product was obtained after a weak acid workup. The synthesis of ambelline has the potential to provide new pathways for treatment of Alzheimer’s disease.

Le travail de cette thèse consiste en la synthèse et la désymétrisation d'arylcylohexa-2,5-diène, méthodologie pouvant donner accès à différentes classes d'alcaloïdes. Ces arylcyclohexa-2,5-diènes sont obtenus à partir de biaryles par réduction de Birch alkylante. Dans un premier temps, une étude systématique de cette réaction a été effectuée sur des biaryles substitués par des groupements électrodonneurs. Dans un second temps, les systèmes diéniques ou bis ether d'énols obtenus par cette voie ont été fonctionnalisés par différents processus : dihydroxyloation, iodocyclisation, amination oxydante, et en particulier par hydroamination, réaction réalisée de manière diastéréocontrôlée et menant au squelette hydrocarboné des crinanes. Une réaction de type Mannich a aussi été exploitée pour mener à un système tricyclique, précurseur possible des morphinanes.

Dans le cadre de cette thèse, nous nous sommes intéressés à la synthèse totale d'alcaloïdes de type crinine, de la famille des Amaryllideceae. Notre stratégie de synthèse repose la formation d'un cycle à sept chaînons, avec création concomitante du carbone quaternaire caractéristique de cette famille, par réaction de Heck intramoléculaire. Ainsi, dans un premier temps, les synthèses de l'oxocrinine et de l'oxomaritidine ont été effectuées en sept étapes avec, respectivement, 22. 1% et 14. 8% de rendement. Dans un deuxième temps, la crinine, la maritidine et la buphanisine, éther méthylique de la crinine, ont été formées, en deux étapes, par réduction diastéréosélective d'énone suivie de l'inversion de configuration de l'alcool par SN2 ou par réaction de Mitsunobu. Les synthèses de la flexinine et de l'augustine, alcaloïdes possédant une fonction époxyde, ont été envisagées de multiples façons pour conduire finalement à l'époxy-alcool avec la stéréochimie adéquate. Malheureusement, les premiers essais d'inversion de configuration de l'alcool ont échoué et, n'ont donc pas permis d'accéder aux molécules naturelles cibles. Enfin, la synthèse de ces alcaloïdes a permis, par réarrangement de type diénone-phénol, de former à partir des intermédiaires spirodiénones, des dérivés biaryliques pontés, analogues de la buflavine, alcaloïdes des Amaryllidaceae
Within the framework of this thesis, we were interested in the total synthesis of crinine-type alkaloids, belonging to Amaryllideceae plants. Our strategy is based on the formation of seven membered ring and on the simultanous creation of critical quaternary carbon by intramolecular Heck reaction. First, oxocrinine and oxomaritidine have been synthetised in seven steps in, respectively, 22. 1% and 14. 8% overallyield. Secondly, maritidine, crinine, its methyl ether, the buphanisine have been obtained, in two steps, by diastereoselective enone reduction, followed by SN2 alcohol inversion or by Mitsunobu reaction. The flexinine and augustine syntheses were considered in different ways to get, finally, the epoxy-alcohol with the correct stereochemistry. Unfortunately, the first attempts of alcohol inversion failed, our synthetical target was not obtained. Finally, dienone-phenol rearrangement of the synthetised spirodienone intermediates led to the bridged biaryl compounds, buflavine analogs

Thesis (M.S.)--University of Maryland, College Park, 2005.
Thesis research directed by: Dept. of Chemistry and Biochemistry. Title from t.p. of PDF. Includes bibliographical references. Published by UMI Dissertation Services, Ann Arbor, Mich. Also available in paper.

Il presente elaborato si propone di analizzare il racconto dalla scrittrice argentina María Teresa Andruetto (Premio Hans Christian Andersen 2012) El país de Juan, nell’edizione pubblicata dalla casa editrice spagnola Anaya nel 2003. Nel 2014 ne è stata proposta la traduzione in italiano con il titolo Il paese di Juan, ad opera di Ilide Carmignani. La storia, che narra di due bambini costretti a migrare dalla campagna alle favelas argentine (Villas), si presenta come una vera e propria sfida traduttiva per il contrasto tra la poeticità del linguaggio e il realismo del mondo raccontato ed il forte legame con il contesto locale in cui è inserita. Lo studio consta di tre capitoli principali: nel primo si approfondiscono la vita, le opere, lo stile e la concezione della letteratura della Andruetto. Dopo aver impostato tale cornice stilistica e contestuale, si prosegue, nel secondo capitolo, con l’analisi del testo originale, dove vengono messi in luce gli aspetti formali e stilistici della scrittura, le tematiche, gli elementi grafici, le illustrazioni e il contesto storico-sociale. Si passa poi, nel terzo ed ultimo capitolo, ad un’analisi della traduzione italiana del libro rispetto alla capacità di ricreare un tipo di linguaggio altamente innovativo, la salvaguardia delle figure retoriche, degli aspetti grafici e dei riferimenti culturali, elementi di fondamentale importanza per creare una traduzione in grado di aprire gli orizzonti del giovane lettore. Inoltre, si confrontano i glossari della versioni spagnola e italiana evidenziandone differenze e affinità. Si pone infine l’accento sull’indiscutibile abilità della Carmignani nel saper mantenere la dicotomia testuale tra realismo e mistero, riferendosi anche all’importanza della collaborazione tra lo scrittore e il traduttore, legame che senza dubbio è possibile cogliere nella traduzione Il paese di Juan.

Os efeitos individuais e interativos dos parâmetros ambientais físicos e químicos, como temperatura, intensidade luminosa, salinidade e concentração de fósforo inorgânico dissolvido na água do mar, na produção de proteínas, carboidratos, acúmulo de fósforo tecidual e taxa de absorção do fósforo inorgânico disponível no meio de cultura em Gelidium crinale (Turner) Lamouroux, foram investigados durante um período de sete dias de cultivo laboratorial, em condições controladas. A ação dos parâmetros abióticos foi analisada de três maneiras diferentes. A primeira avaliação integrou a ação de temperatura, intensidade luminosa e fósforo inorgânico dissolvido, mantendo-se fixa a salinidade em 25 ups, onde se constatou que em todos os componentes químicos algais ocorreram interações de terceira ordem. O incremento de 2,28 a 2,67 % nos teores de proteínas foram obtidos à temperatura de 25 °C e 12 μmol m-2 s-1 de intensidade luminosa, diminuindo com a elevação da intensidade luminosa para 40 μmol m-2 s-1. Para carboidratos, ocorreram interações significativas entre os três parâmetros, com um aumento de 6,85 % sendo registrado a 25 °C de temperatura, 24 μmol m-2 s-1 de intensidade luminosa e 10,0 μM de fósforo inorgânico. O aumento máximo na taxa de fósforo tecidual (0,56 %) ocorreu em talos cultivados nas menores temperatura e intensidade luminosa e na maior concentração de fósforo inorgânico dissolvido. Com relação à intensidade luminosa, foi observada uma correlação negativa entre proteínas e carboidratos. A segunda avaliação estabeleceu a ação independente e sinérgica de temperatura, salinidade e fósforo inorgânico disponível no meio de cultivo, fixando-se a intensidade luminosa em 24 μmol m-2s-1. A maior produção de proteínas ocorreu em cultivos onde a temperatura foi de 25 °C, com uma concentração de 5,0 e 10,0 μM de fósforo inorgânico dissolvido e salinidade entre 15 e 20 ups, cujos valores médios do incremento variaram entre 2,62 a 2,83 % peso seco de alga, resultando em uma interação de terceira ordem altamente significativa. Para carboidratos a elevação de 6,85 % em sua concentração está associada à maior temperatura (25 °C), maior salinidade (25 ups) e maior quantidade de fósforo inorgânico disponível no meio de cultivo (10,0 μM). Contudo, não foi observada uma interação de terceira ordem através da análise estatística. Para esta biomolécula observaram-se interações de segunda ordem altamente significativa (P < 0,005) entre temperatura e diferentes concentrações de fósforo inorgânico e entre temperatura e salinidade (P < 0,000). O acúmulo de fósforo nos talos da alga foi menor durante os cultivos em que a salinidade foi de 25 ups,nas temperaturas de 20 e 25 °C e concentração de fósforo disponível de 2,5 μM, com percentuais entre 0,08 a 0,11 % em peso de cinzas. O maior incremento ocorreu na menor temperatura, associada à baixa salinidade e alta concentração de fósforo inorgânico no meio. O coeficiente de correlação de Pearson revelou correlações positivas, altamente significativas (P < 0,001) entre teor de proteína, temperatura e disponibilidade de fósforo inorgânico no meio de cultivo. Para carboidratos, as correlações foram positivas com os três parâmetros abióticos. Para fósforo tecidual somente com o fósforo inorgânico disponível no cultivo foi que ocorreu uma relação positiva; com os outros dois parâmetros esta correlação foi negativa. Entre os componentes químicos encontrados nas algas, proteínas e carboidratos apresentaram uma relação positiva, porém fósforo tecidual apresentou uma correlação negativa com ambos, embora com proteínas esta relação não tenha sido significativa. A terceira avaliação estudou a ação individual e o sinergismo entre os parâmetros ambientais, temperatura, intensidade luminosa e salinidade, a uma concentração fixa de fósforo inorgânico disponível no meio de cultivo (10,0 μM), sobre a composição química, bem como na taxa de absorção de fósforo inorgânico disponível. Observou-se a ocorrência de interações de terceira ordem em todos as variáveis estudadas. O teor de proteínas apresentou um aumento de 3,72 % durante o período de cultivo, passando de 20,63 % antes do cultivo, para 24,35 % após o término do experimento, principalmente nas condições de 25 °C de temperatura, 12 μmol m-2s-1 de intensidade luminosa e 15 ups de salinidade. Para carboidratos, nas condições de baixa intensidade luminosa (12 μmol m-2s- 1), a uma temperatura de 20 °C e salinidades de 10 e 15 ups, foram registrados valores inferiores à amostra controle, caracterizando um consumo desta biomolécula por parte das algas. Nestas mesmas condições ambientais, foram registrados os maiores teores de fósforo tecidual, variando entre 0,86 a 1,09 % do peso das cinzas. As maiores taxas de absorção do fósforo do meio ocorreram na salinidade de 25 ups e 25 °C de temperatura, diminuindo da intensidade luminosa de 12 μmol m-2s-1 para 40 μmol m-2s-1. As maiores concentrações de fósforo inorgânico residual na água do meio de cultivo ocorreram nas salinidades de 10 e 15 ups, em todas as intensidade luminosas e temperaturas estudadas. Através do coeficiente de correlação de Pearson, observou-se que os teores de proteínas apresentaram uma forte correlação negativa com a intensidade luminosa e positiva com a temperatura e salinidade, embora com esta última não tenha sido significativa. Para carboidratos, as correlações com os parâmetros abióticos foram todas positivas. Correlações negativa e positiva, não significativas, foram observadas entre esta biomolécula e o teor de proteínas e a taxa de absorção de fósforo disponível no meio, respectivamente. Por outro lado, com fósforo tecidual, ocorreu uma correlação negativa, altamente significativa. Este estudo mostra o estado fisiológico de Gelidium crinale e contribui para o estabelecimento das melhores condições de cultivo para produção de proteína, carboidrato e fósforo tecidual e indicação do uso racional de nutrientes, fornecendo informações para a otimização de processos de maricultura, tanto em termos de cultivo bem sucedido de algas, quanto de redução no impacto sobre o ambiente.
The individual and interactive effects of the physical and chemical environmental parameters such as temperature, light intensity, salinity and dissolved inorganic phosphorus concentration in the sea water, on protein and carbohydrate production, tissue phosphorus accumulation and absorption rate of inorganic phosphorus available in the culture medium by Gelidium crinale, were investigated in laboratory cultures, for seven days, under controlled conditions. The action of the abiotic parameters was analyzed in three different ways. The first evaluation integrated the action of temperature, light intensity and dissolved inorganic phosphorus, at a constant salinity of 25 ups, where third-order interactions were verified for all algal chemical compounds. The increase of 2,28 to 2,76 % in the protein content was obtained at a temperature of 25 °C and 12 μmol m-2 s-1 of light intensity, decreasing with an increase in light intensity towards 40 μmol m-2 s-1. For carbohydrates there was a significant interaction among the abiotic parameters, with a maximum increment of 6.85 % at 25 °C of temperature, 24 μmol m-2 s-1 of light intensity and 10.0 μM of inorganic phosphorus. The highest increase on tissue phosphorus concentration (0.56 %) occurred in thalli grown under the lowest temperature and light intensity and the highest dissolved inorganic phosphorus concentration used in this study. With regard to light intensity, was observed a negative correlation between proteins and carbohydrates. The second evaluation established the independent and synergic action of temperature, salinity and available inorganic phosphorus, setting the light intensity at 24 μmolm-2s-1. The maximum production of proteins occurred in cultures where the temperature was 25 °C, with a concentration of 5,0 and 10,0 μM of dissolved inorganic phosphorus and salinity between 15 and 20 ups, with values varying among 2,62 to 2,83% of algae dry weight, resulting in a highly third order significant interaction. For carbohydrates the elevation of 6,85% in concentration is associated to the greatest temperature (25 °C), salinity (25 psu) and amount of available inorganic phosphorus in the culture (10,0μM). However, a third-order interaction was not observed in the statistical analysis. For this biochemical compound, only a second order interaction was observed between temperature and inorganic phosphorus concentrations (P < 0,005) and between temperature and salinity (P < 0,000). The phosphorus accumulation in the thalli was minor during growth under salinity of 25 ups, temperatures of 20 and 25 °C and dissolved inorganic phosphorus concentration of 2,5 μM, with values of 0,08 and 0,11% on an ash weight basis. The greatest increase occurred in the smallest temperature, associated to low salinity and high inorganic phosphorus concentration in the culture. The Pearson’s correlation coefficient revealed highly significant (P < 0,001) positive correlations among protein content, temperature and inorganic phosphorus availability in the growth medium. For carbohydrates, correlations were positive with all three abiotic parameters. For tissue phosphorus, a positive correlation occurred only with dissolved inorganic phosphorus; with temperature and salinity the correlations were negative. Among the chemical components present in the algae, proteins and carbohydrates showed a positive relation, while tissue phosphorus presented a negative correlation with both, although this correlation was not significant with regard to protein. The third evaluation looked at the individual and synergic action among the environmental parameters of temperature, light intensity and salinity, at a constant concentration of dissolved inorganic phosphorus (10,0 μM) on the chemical composition, as well as in absorption rates of available inorganic phosphorus. Third-order interactions were observed for all the studied variables. Proteins presented an increase of 3,72% during the growth period, ranging from 20,63 %, before cultivation to 24,35% by the end of the experiment, especially at 25 °C of temperature, 12 μmolm-2s-1 of light intensity and salinity of 15 ups. For carbohydrates, under conditions of low light intensity (12 μmolm-2s- 1), a temperature of 20 °C and salinities of 10 and 15 ups, concentrations were below the control values, characterizing a consumption of this component by the algae. In these same environmental conditions, the largest quantity of tissue phosphorus was registered, varying from 0,86 to 1,09% of ash weight. The highest absorption rates of the phosphorus available in the medium took place under salinity of 25 ups and 25 °C of temperature, decreasing from a light intensity of 12 μmolm-2s-1 to 40 μmolm-2s-1. The highest concentrations of residual inorganic phosphorus in the medium seawater were measured for salinities of 10 and 15 ups, for all the light intensities and temperatures studied. Analysis of the Pearson’s correlation coefficient demonstrated that proteins content had a strong negative correlation with light intensity and positive correlation with temperature and salinity, although with this last one the correlation was not significant. For carbohydrates, the correlations with the abiotic parameters were all positive. Negative and positive correlations, though not significant, were observed among this biochemical component and protein content and absorption rate of available inorganic phosphorus, respectively. On the other hand, with tissue phosphorus, carbohydrates showed a highly significant negative correlation. This study reveals the physiological behavior of Gelidium crinale, and contributes to the establishment of the optimum conditions of the growth medium and to the rational use of nutrients, providing valuable information for optimizing processes of marine culture, both in terms of successful growth of algae and reduced impact on the environment.