Progress towards a concise total synthesis of subincanadine E is reported. This natural product was first isolated from the Picralima nitida cell suspension culture line in 1982 under the name pericine and later in 2002 from Aspidosperma subincanum as subincanadine E. It is the most potent compound of its class with in vitro cytotoxicity against both murine lymphoma L1210 and human epidermoid carcinoma KB cells (LD50, 0.3 ug/mL and 4.4 ug/mL, respectively) and was found to be six times more potent than codeine as an opiate agonist in a 3H-naloxone binding study (IC50, 0.6 umol/L). The first-generation synthesis produced an undesired internal olefin that, upon attempted isomerization, catalyzed an unusual intermolecular Diels-Alder reaction. A revised second-generation synthesis employed (±)-harmicine and showcased an intramolecular Pd-catalyzed cross-coupling reaction that furnished an unanticipated 5-membered ring instead of the predicted 6-membered ring via methylene linker activation. Further studies utilizing an amide intermediate and organocuprate chemistry produced no desired carbon-carbon bond formation. A third-generation synthesis was carried out from enantiopure (S)-carvone. This route explored regioselective oxime formation and protecting group manipulations for a subsequent Beckmann rearrangement, which provided the first access to 5-amino derivatives of carvone. An intramolecular Pd-catalyzed cross-coupling reaction was performed to construct the aza-bicycle prior to indole installation. Contingent on its success, indole introduction and a double alkylation would provide an akuammicine-like scaffold that can ring-open upon hydride exposure to afford (15S)-subincanadine E in 16 overall steps. This work accomplished 10 steps toward the first total asymmetric synthesis of (15S)-subincanadine E.

Sprout control is essential for successful management of stored potatoes. This study examined the effect of dill weed, spearmint and clove essential oils on sprouting of potatoes. Extracts of steam distilled dill weed whole plants containing 41.5-42.7% of S-(+)-carvone and spearmint foliage extracts containing 97.2-97.6% of R-(-)-carvone, were applied to tubers in a series of experiments using either 1-L glass jars or 63-L steel drums. The composition of the essential oils was consistent between years but evaporation rate varied among the oils as dill weed extract evaporated the fastest while clove oil evaporated the slowest under the same conditions. After exposure to essential oil treatments, tuber sprout number and weight were assessed and compared to untreated control and tubers treated with commercially marketed clove oil product (Biox-CTM, containing 78.5-82.3% eugenol). Applications of 32.5 and 47.6 mg L-1 headspace of dill weed oil and 21.5 and 22.3 mg L-1 headspace of spearmint oil achieved 50% reduction in 'Russet Burbank' sprout weight and sprout number respectively, 30 days after the initial treatment. Tubers stored in environments with 60-240 mg L-1 headspace of dill weed or spearmint oils suppressed sprouting at least 5 weeks longer than that of the controls. In 63-L steel drums, repeated dill and spearmint oil vapor treatments effectively and consistently suppressed sprouting of 'Russet Norkotah' and 'Piccolo' tubers for 7-8 months when doses were 25 mg L-1 headspace or higher and when treatments were repeated at least every four weeks. Within this range, sprout suppression was not sensitive to treatment variations, and, therefore, an optimal treatment level could not be determined. Clove oil was less effective in suppressing sprouting, likely due to its slower vaporization compared to dill and spearmint oils. Essential oil treatment effects on seed tuber viability were evaluated on 'Piccolo'. Tubers were planted after exposure to dill or spearmint oil vapor environments ranging from 15-240 mg L-1 headspace for seven days. There were no adverse effects on seed viability at doses less than 120 mg L-1 headspace. Although environments with <120 mg L-1 headspace had no significant adverse impact on sprouting, sprout emergence was delayed at higher doses. Dill weed and spearmint oils could potentially be used as potato sprout inhibitors but further studies are needed to demonstrate its commercial feasibility.

Sprout control is essential for successful management of stored potatoes. This study examined the effect of dill weed, spearmint and clove essential oils on sprouting of potatoes. Extracts of steam distilled dill weed whole plants containing 41.5-42.7% of S-(+)-carvone and spearmint foliage extracts containing 97.2-97.6% of R-(-)-carvone, were applied to tubers in a series of experiments using either 1-L glass jars or 63-L steel drums. The composition of the essential oils was consistent between years but evaporation rate varied among the oils as dill weed extract evaporated the fastest while clove oil evaporated the slowest under the same conditions. After exposure to essential oil treatments, tuber sprout number and weight were assessed and compared to untreated control and tubers treated with commercially marketed clove oil product (Biox-CTM, containing 78.5-82.3% eugenol). Applications of 32.5 and 47.6 mg L-1 headspace of dill weed oil and 21.5 and 22.3 mg L-1 headspace of spearmint oil achieved 50% reduction in 'Russet Burbank' sprout weight and sprout number respectively, 30 days after the initial treatment. Tubers stored in environments with 60-240 mg L-1 headspace of dill weed or spearmint oils suppressed sprouting at least 5 weeks longer than that of the controls. In 63-L steel drums, repeated dill and spearmint oil vapor treatments effectively and consistently suppressed sprouting of 'Russet Norkotah' and 'Piccolo' tubers for 7-8 months when doses were 25 mg L-1 headspace or higher and when treatments were repeated at least every four weeks. Within this range, sprout suppression was not sensitive to treatment variations, and, therefore, an optimal treatment level could not be determined. Clove oil was less effective in suppressing sprouting, likely due to its slower vaporization compared to dill and spearmint oils. Essential oil treatment effects on seed tuber viability were evaluated on 'Piccolo'. Tubers were planted after exposure to dill or spearmint oil vapor environments ranging from 15-240 mg L-1 headspace for seven days. There were no adverse effects on seed viability at doses less than 120 mg L-1 headspace. Although environments with <120 mg L-1 headspace had no significant adverse impact on sprouting, sprout emergence was delayed at higher doses. Dill weed and spearmint oils could potentially be used as potato sprout inhibitors but further studies are needed to demonstrate its commercial feasibility.

No description available.

The essential oils from the aerial parts of leaves and flowers of Poiretia latifolia and Poiretia tetraphylla, were analysed by GC, GC/MS and Enantioselective Gas Chromatography (EGC). Forty five constituents were identified from the essential oils. The major constituents of the essential oils of P. latifolia, dominated by monoterpenos, were carvone (50-69%), limonene (13-24%) and trans-dihidrocarvone (8- 18%). The essential oil from leaves of P. tetraphylla was dominated by sesquiterpenes, where nerolidol-E (17-30%), β-cariofilene (5-16%) and germacrene-D (3-9%) were the major constituents. The essential oils from P. latifolia shows activity against brine shrimp assay (LC50 = 67 - 85 μg mL-1), and exhibited antimicrobial activity against some gram-positive and gram-negative bacteria, and some yeasts, while the essential oil from leaves of P. tetraphylla was inactive. / Os óleos essenciais das partes aéreas de folhas e flores de Poiretia latifolia e Poiretia tetraphylla foram analisados por CG, CG/EM e Cromatografia Gasosa Enantiosseletiva (CGE), sendo que foram identificados quarenta e cinco componentes destes óleos voláteis. Os componentes principais dos óleos voláteis de P. latifolia, ricos em monoterpenos, foram a carvona (50-69%), o limoneno (13-24%) e a trans-dihidrocarvona (8-18%). O óleo volátil das folhas de P. tetraphylla teve uma composição dominada por sesquiterpenos, onde o nerolidol-E (17-30%), o β-cariofileno (5-16%) e o germacreno-D (3-9%) foram os componentes principais. Os óleos voláteis de P. latifolia mostraram uma atividade frente a Artemia salina bastante significativa (LC50 = 67 - 85 μg mL-1), exibindo também atividade antimicrobiana contra algumas bactérias gram-positivas e gram-negativas, e alguns fungos, enquanto o óleo volátil de folhas de P. tetraphylla foi inativos para estes ensaios.

Made available in DSpace on 2015-05-14T12:59:24Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 1952542 bytes, checksum: cbb5dfafac619fd1f5d9b4ef4efbccf2 (MD5) Previous issue date: 2011-02-28 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Enantiomers are asymmetric compounds that present mirror images of each other, not overlapping and different behaviors in chiral environments, resulting in esterioseletiva discrimination and different biological effects. The carvone is a monoterpene, a constituent of many essential oils found in nature as two enantiomers, (S)-(+)-carvone and (R)-(−)-carvone. The inflammation, a physiological response of the organism, when it occurs exaggerated or inappropriated ways may promote tissue damage and associated pathologies. An example of inflammatory disease is asthma, an immediate hypersensitivity process of the airways and the conventional treatments have significant adverse effects. The aim of this study was to evaluate the carvone enantiomers in experimental models of inflammation and hypersensitivity of the airways. To investigate the effect anti-inflammatory the following parameters were evaluated: NO production by cells J774.A1, paw oedema formation induced by carrageenan, zymosan, compound 48/80 and histamine, cell migration and cytokines production (TNF-α and IL-1β) in the experimental model of peritonitis induced by zymosan in Swiss mice. To evaluate the anti-asthmatic activity of these enantiomers, it was used the experimental model of asthma induced by ovalbumin and the following parameters were analyzed: bronchoalveolar lavage (BAL), mucus production, OVA-specific IgE synthesis, cytokine production (IL-13, IFN-γ and IL-10). The results showed that both enantiomers were able to reduce NO production, inhibit the paw oedema induced by phlogistic agents and inhibit cell migration to the peritoneum, but only the (R)-(−)-carvone was able to reduce levels of TNF-α. In the murine model of asthma, the (R)-(−)-carvone, was able to reduce the cellularity of the BAL, modulate the OVA-specific IgE production, reduce the cell infiltration and mucus in the lungs and further increase the IL-10. However, although the (S)-(+)-carvone has reduced the BAL cellularity and increased IFN-γ levels, it was unable to reduce the cell infiltration in the lung and increase the mucus production. Therefore, both enantiomers of carvone showed anti-inflammatory effect, although only the (R)-(−)-carvone showned potential anti-asthmatic. Additionally, the results presented by (S)-(+)-carvone, revealed a potential adverse effect of this enantiomer in the experimental model of asthma. / Enantiômeros são compostos assimétricos que apresentam a particularidade de serem imagens especulares um do outro, não sobreponíveis e por terem comportamentos diferentes em ambientes quirais, resultando frequentemente na discriminação esterioseletiva e diferentes efeitos biológicos. A carvona é um monoterpeno, constituinte de muitos óleos essenciais e encontrada na natureza na forma de dois enantiômeros: (S)-(+)-carvona e (R)-(-)-carvona. A inflamação uma resposta fisiológica do organismo, quando ocorre de forma exacerbada ou inapropriada pode promover dano tecidual e patologias associadas. Um exemplo de doença inflamatória importante é a asma, um processo hipersensibilidade imediata nas vias aéreas e que tratamentos convencionais apresentam efeitos colaterais importantes. O objetivo desse trabalho foi avaliar os enantiômeros da carvona em modelos de inflamação e de hipersensibilidade das vias aéreas. Para investigar a atividade anti-inflamatória das substâncias os seguintes parâmetros foram avaliados: produção de NO por células J774.A1, formação de edema de pata induzido por carragenina, zimosan, composto 48/80 e histamina, migração de células e produção das citocinas (TNF-α e IL-1β) no modelo de peritonite induzida por zimosan, em camundongos Swiss. Para avaliar a atividade anti-asmática dos enantiômeros, foi utilizado o modelo de asma experimental induzido por ovalbumina e analisado os seguinte parâmetros: celularidade do lavado bronco alveolar (BAL), produção de muco, síntese de IgE OVA-específica, produção de citocinas (IL-13, IFN-γ e IL-10). Os resultados demonstraram que ambos os enantiômeros foram capazes de reduzir a produção de NO, inibir o edema de pata induzido pelos agentes flogísticos utilizados e inibir a migração de células para o peritônio, porém apenas a (R)-( )-carvona foi capaz de reduzir os níveis de TNF-α. No modelo murino de asma alérgica, a (R)-(−)-carvona, foi capaz de reduzir a celularidade do BAL, modular a produção de IgE OVA-específica, reduzir o infiltrado de células e muco no pulmão e ainda, aumentar os níveis de IL-10. Porém, embora a (S)-(+)-carvona, tenha reduzido a celularidade do BAL e aumentado os níveis de IFN-γ, ela não foi capaz de reduzir o infiltrado de células no pulmão e ainda, aumentou a produção de muco. Portanto, ambos enantiômeros da carvona apresentaram efeito anti-inflamatório, embora apenas a (R)-(-)-carvona tenha apresentado potencial anti-asmático e ainda, os resultados apresentados pela (S)-(+)-carvona, revelaram um potencial efeito adverso desse enantiômero em modelo experimental de asma.

Submitted by Viviane Lima da Cunha (viviane@biblioteca.ufpb.br) on 2016-06-17T13:53:28Z No. of bitstreams: 1 arquivototal.pdf: 2902409 bytes, checksum: e69de912594ba6926693bade26900ea3 (MD5) / Made available in DSpace on 2016-06-17T14:11:24Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 2902409 bytes, checksum: e69de912594ba6926693bade26900ea3 (MD5) Previous issue date: 2016-02-26 / Financiadora de Estudos e Projetos - Finep / The epoxy-carvone (EC) is a monoterpene present in herbs with proven pharmacological activity in the CNS, including, antinociceptive and anticonvulsant. This substance has chiral centers that permit the generation of four stereoisomers, called (+)-cis-EC, (-)-cis-EC, (+)-trans-EC and (-)-trans-EC, whose comparative anticonvulsant effects have never been studied. This work aims to investigate in a comparative way the anticonvulsant activity of enantiomers of EC cited in experimental models of chemical and electrical induction of seizures in mice and quantifying pro-inflammatory cytokines and perform histopathological analysis of the treated animals. In the test of the seizures induced by pentylenetetrazol, all stereoisomers tested (300 mg/kg; ip) were effective in protecting seizures, increasing the latency for appearances thereof. Since the test of the seizures induced by pilocarpine, substances (+)-cis-EC, (+)-trans-EC and (-)-trans-EC were most prominent in the reduction of parameters related to the activation of cholinergic receptors, and increase the latency to onset of seizures. No significant results were obtained in the test of seizures induced by strychnine, suggesting that possibly these drugs do not act in glycine receptors. In the maximum atrial electroshock model, difference was evident in the effect of EC stereoisomers and despite all reduce the duration of significantly convulsions, substances (+)-trans-EC and (-)-trans-EC showed a reduction even more pronounced. In the kindling test, (+)-cis-EC and (-)-cis-EC reduced the average scores presented with a small but noticeable, especially (+)-cis-EC. The stereoisomer (+)-cis-EC decreased levels of proinflammatory cytokines IL-1β, IL-6 and TNFα in the kindling test, whereas comparatively (-)-cis-EC did not reduce the amount of IL -1β. Histopathological analysis showed greater hippocampal neuronal protection for those treated with (+)-cis-EC. The group treated with (-)-cis-CE exhibited inflammatory components in this tissue, which again lists (+)-cis-EC as a promising, compared. Thus, these results show that the EC stereoisomers has similar anticonvulsant potential, especially (+)-cis-EC, which interferes possibly potentiating inhibitory pathways or inhibiting excitatory pathways, in addition to changing levels of cytokines involved in epileptic condition and promote neuronal protection mechanisms that require further investigation. / A epóxi-carvona (EC) é um monoterpeno presente em plantas aromáticas com atividades farmacológicas já comprovadas no sistema nervoso central, entre elas, antinociceptiva e anticonvulsivante. Esta substância apresenta centros quirais que possibilitam a geração de quatro estereoisômeros, denominados (+)-cis-EC, (-)-cis-EC, (+)-trans-EC e (-)-trans-EC, cujos efeitos anticonvulsivantes comparativos nunca foram estudados. Este trabalho visa investigar de forma comparativa a atividade anticonvulsivante dos citados estereoisômeros da EC em modelos experimentais de indução química e elétrica de convulsão em camundongos, bem como quantificar citocinas pró-inflamatórias e realizar análise histopatológica dos animais tratados. No teste das convulsões induzidas pelo pentilenotetrazol, todos os estereoisômeros testados (300 mg/kg; i.p.) foram efetivos na proteção das convulsões, aumentando a latência para surgimentos das mesmas. Já no teste das convulsões induzidas pela pilocarpina, as substâncias (+)-cis-EC, (+)-trans-EC e (-)-trans-EC tiveram maior destaque na redução de parâmetros relacionados à ativação de receptores colinérgicos, além de aumentarem a latência para início das convulsões. Não foram obtidos resultados significativos no teste das convulsões induzidas pela estricnina, sugerindo-se que possivelmente estas drogas não atuem em receptores de glicina. No modelo do eletrochoque auricular máximo, evidenciou-se diferença no efeito dos estereoisômeros da EC e apesar de todos reduzirem a duração das convulsões de forma significativa, as substâncias (+)-trans-EC e (-)-trans-EC apresentaram uma redução ainda mais acentuada. No teste do “kindling”, (+)-cis-EC e (-)-cis-EC reduziram a média dos escores apresentados, com pequeno mas visível destaque para (+)-cis-EC. O estereoisômero (+)-cis-EC diminuiu os níveis das citocinas pró-inflamatórias IL-1β, IL-6 e TNFα no teste do “kindling”, enquanto, comparativamente, (-)-cis-EC não reduziu a quantidade de IL-1β. A análise histopatológica do hipocampo evidenciou proteção neuronal maior para os tratados com (+)-cis-EC. O grupo que recebeu (-)-cis-EC exibiu componentes inflamatórios neste tecido, o que elenca mais uma vez (+)-cis-EC como promissor, comparativamente. Sendo assim, esses resultados mostram que os estereoisômeros da EC tem similar potencial anticonvulsivante, com destaque para (+)-cis-EC, que possivelmente interfere potencializando vias inibitórias ou inibindo vias excitatórias, além de alterar os níveis de citocinas envolvidas no processo epileptogênico e promover proteção neuronal por mecanismos que requerem maiores investigações

No description available.

In 1996-2000 during expeditions were found and described 123 Carum carvi habitats. Mostly common caraway is found in pasture type habitats of Cynosurion cristati confederation communities. Plants of Carum carvi cenopopulations are characterized by wide diversity of phenotypic traits strongly influenced by ecological conditions and anthropogenic activity in natural habitats. The most stable parameters are weight of 1000 fruit and biochemical composition of essential oil. Essential oil synthesis in fruits is positively affected by warm and dry weather at the stage of caraway flowering – fruit ripening, carvone content – by warm and wet weather. The identified morphological types of Carum carvi leaves were as follows: normal, dill and parsley. Early-season caraway forms in comparison to others distinguished for the lowest height, fruit weight and total yield, but had the highest carvone content in fruit essential oil. Pink petals are characteristic for early-season caraway cenopopulations. White petal color, greater pigments amount in leaves, higher fruit productivity, as well as essential oil and carvone output characterize medium late and late forms. Various caraway genotypes with different levels of leaf carotinoids, chlorophyll content and ratio, anthocianins amount in petals, different reaction to cold and lighting stress reveal specific adaptive plasticity of caraway. Caraway intercenopopulation genetic diversity was determined at the molecular level.

Waxflower (Chamelaucium spp. and hybrids) is the singlemost important Australian export cut-flower. The major problem in waxflower trading is flower abscission after harvest. While several factors are involved, ethylene production resulting from preharvest infection with the fungus Botrytis cinerea is the most important cause. The general objectives of this study were to investigate the biology of Botrytis infecting waxflower flowers and potential elicitation of host defence against this pathogen. Effects of anti-ethylene and S-carvone treatments on Botrytis-induced flower abscission were also evaluated. Infection of flowers by Botrytis was studied on two waxflower cvs. Mullering Brook and My Sweet Sixteen using light and electron microscopy. Conidial germination and protoappressorial formation occurred within 8 h post-inoculation (hpi). Infection of most floral organs, including petals, anthers and filaments, stigma, and hypanthium, was within 24 hpi. Infection cushions on stamen bases were formed at 36 hpi by saprophytic hyphae that originated from anthers. This infection route probably gives rise to the typical tan-coloured Botrytis symptoms that appear to radiate from this part of the flower. Subcuticular hyphae were present at very high density near stamen bases. They evidently resulted at multiple penetrations from single infection cushions. Flower abscission occurred at 72 hpi. At this time, floral tube tissues remained uninfected. This temporal pattern infers the possible transmission of a signal (e.g. ethylene) upon Botrytis infection (6–36 hpi) that intiates a defence response of shedding infected flowers (72 hpi). Susceptibility of waxflower before and after harvest to B. cinerea under various environmental conditions (laboratory, greenhouse, and field) was investigated. Flowers, either on plants or on cut stems showed similar susceptibility to B. cinerea and abscised under cool temperatures (~20 ºC) and high humidity (>95% RH) conditions following infection. Compared to cv. Mullering Brook, cv. My Sweet Sixteen was somewhat more resistant to B. cinerea infection under field conditions. Constitutive and inducible antifungal compounds in waxflower flower tissues were screened in cvs. CWA Pink, Stephan’s Delight, Mullering Brook and My Sweet Sixteen using thin layer chromatography bioassays with isolates of B. cinerea and Alternaria alternata (pathogenic) and Cladosporium cladosporioides (non-pathogenic). Common inhibition zone observed at Rf 0.28–0.38, 0.46–0.56 and 0.67–0.76 contained phenolic compounds. There were at least five (cv. Mullering Brook) and one (cv. My Sweet Sixteen) inducible antifungal phenolic compounds as judged by increases in inhibition area as a result of B. cinerea infection and methyl jasmonate treatment. The total areas of B. cinerea- and MeJA-induced inhibition zones were approximately 2.0- and 2.5-folds greater, respectively, than zones from control flowers. Preharvest sprays of three different known host plant defence elicitors, methyl jasmonate (MeJA), benzothiadiazole (BTH), and silicon (Si), were applied to waxflower cvs. Mullering Brook and My Sweet Sixteen plants. BTH or Si sprays generally had no significant effect on postharvest Botrytis severity on either cultivar. MeJA sprays did not reduce B. cinerea on cv. Mullering Brook. MeJA slightly suppressed B. cinerea on cv. My Sweet Sixteen at 500 and 750 µM. Overall, field applications of these host plant defence elicitor chemicals as spray treatments had little effect on vase life, water uptake and relative fresh weight of the cut sprigs. Moreover, they did not appreciably suppress B. cinerea or associated postharvest floral abscission. The efficacy of combined elicitor treatments and combined pre- and postharvest MeJA treatments were assessed. Preharvest foliar applications of MeJA (1000 µM; 2 or 4 times), MeJA (1000 µM) combined with BTH (150 mg/L), and MeJA combined with Si (1500 mg SiO2/L) generally did not suppress postharvest B. cinerea development and flower abscission from harvested sprigs. A pre- plus post-harvest 1000 µM MeJA spray treatment consistently but only slightly suppressed B. cinerea infection on flowers from both pot- and field-grown plants. Pre- and post-harvest MeJA treatments reduced B. cinerea development, but increased flower abscission. Combined MeJA and anti-ethylene treatments were then screened for potential to suppress B. cinerea while preventing flower abscission. However, the combined MeJA and 1-MCP treatment reduced neither Botrytis disease nor flower abscission on sprigs from pot- and field-grown plants. The combined MeJA and STS treatment reduced disease severity for up to 6 days on sprigs harvested from pot-grown plants but tended to increase Botrytis severity on sprigs from field-grown plants 6 days after inoculation. Antifungal effects of the essential oil S-carvone against B. cinerea germination and mycelial growth were demonstrated in vitro. Inhibition increased with increasing S-carvone concentrations from 0.64 mM to 5.08 mM. However, in planta, S-carvone concentrations in this range did not affect either Botrytis disease levels or flower abscission on cut waxflower flowers.