Não consta resumo na publicação. / The objective of the present dissertation is to contribute for the enlargment and engrossment of the available data on the drug known as maracujá as well as on its extracts. Comprised topics include comparative morphodiagnostic studies and illustrations for P.alata Dryand., P. quadrangularis L., P. edulis Sims. and P. incarnata L.. The differentiation and characterization of the above mentioned species in terms of chemical composition was accomplished by thin layer chromatographic techniques. Chromatographical profiles were established for flavonoid and alkaloid fractions on the four species in relation to reference standards orientin, isoorientin, vitexin, and isovitexin (for flavonoids), and harman and harmin (for alkaloids). P. alata Dryand. earned a more detailed study. The quantifications of flavonoid and alkaloid fractions were performed densitometricaly by TLC and expressed as orientin and harman, respectively. Pharmacological assays carried out with extracts included acute toxicity and CNS depressor activity.

Made available in DSpace on 2015-05-14T12:59:33Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 8556141 bytes, checksum: e65e66480732c01e37d7e4eeec8f05ac (MD5) Previous issue date: 2012-02-06 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The genus Piper is the largest in the family Piperaceae, with at least 1,000 species distributed particularly in the Neotropical region, where about two thirds of the described species can be found. It is a genus commercially important and with many medical applications. The phytochemical investigation of species of this genus which is so rich in metabolites and has widespread use in folk medicine, besides its various biological activities reported in the literature, can open exciting perspectives for the chemistry, pharmacology and chemotaxonomy. This work reports the phytochemical study of three species of Piper, aiming at the isolation and identification of their chemical constituents as well as the pharmacological evaluation of extracts, fractions and isolated compounds. Through usual chromatographic methods and spectroscopic techniques such as IR and one- and two-dimensional 1H and 13C NMR techniques and comparison with literature data it was possible to isolate and identify five amides and two steroids from the aerial parts of Piper lateripilosum collected in Amapá, all of them isolated for the first time in this species. From Piper mollicomum collected in Paraíba were isolated a new amide and a coumarin of the hexane and chloroform phases of the crude ethanol extract of the leaves, respectively, and a benzoic acid derivative and a aristolactam of the chloroform phase obtained from the crude ethanol extract of the stem of this species. The amide is first reported in the literature, the coumarin for the first time in the genus and the benzoic acid derivative and the aristolactam for the first time in this species. From Piper montealegreanum collected in Belém-PA it was possible to isolate a new chalcone, 3 -methoxy,3,4 ,6 -trihydroxy, 2 ,5 -dimethylchalcone, and reisolate the flavonoids 8-formyl-3 ',5-dihydroxy-7-methoxy-6-methylflavanone; 3 '-formyl-3, 4', 6'-trihydroxy-2- methoxy-5-methylchalcone and (2'-methoxy-3'-formyl-4', 6'-dihydroxy-5'-methyl phenyl) - [3''-(dimethylbut-6''-enyl)- 7- phenyl-(3-hydroxy) -cyclohex-2''-enyl]-methyl-9-one. The extracts, some phases and substances isolated from the species studied were submitted to investigation of antimicrobial and hemolytic activities, and modulator of resistance to antibacterial drugs. / O gênero Piper é o maior da família Piperaceae, com pelo menos 1000 espécies distribuídas especialmente na região Neotropical, onde cerca de dois terços das espécies descritas são encontradas. É um gênero com boa representatividade comercial e muitas aplicações medicinais. A investigação fitoquímica de espécies deste gênero, de tão grande riqueza metabólica e de vasta utilização pela medicina popular, além de suas várias atividades biológicas citadas na literatura, pode abrir perspectivas para a química, farmacologia e quimiotaxonomia. Este trabalho relata o estudo fitoquímico de três espécies de Piper, visando o isolamento e identificação de seus constituintes químicos, bem como a disponibilização de seus extratos, frações e substâncias isoladas, para realização de estudos farmacológicos. Utilizando-se métodos cromatográficos convencionais e técnicas espectroscópicas de IV e RMN de 1H e 13C uni e bidimensionais e a comparação dos dados com a literatura foi possível isolar e identificar das partes aéreas de Piper lateripilosum, coletada no Amapá, cinco amidas e dois esteróides todos isolados pela primeira vez nesta espécie. Da espécie Piper mollicomum, da Paraíba, foram isoladas uma nova amida e uma cumarina, das respectivas fases hexânica e clorofórmica do extrato etanólico bruto das folhas, além de um derivado do ácido benzóico e de uma aristolactama obtidos da fase clorofórmica do caule desta espécie. A amida está sendo relatada pela primeira vez na literatura, a cumarina pela primeira vez no gênero e o derivado do ácido benzóico e a aristolactama pela primeira vez nesta espécie. Das partes aéreas de Piper montealegreanum, coletada em Belém PA, foi possível isolar uma nova chalcona, a 3 -metoxi,3,4 ,6 -triidroxi, 2 ,5 -dimetilchalcona, bem como reisolar os flavonóides 8-formil-3 ,5-diidroxi-7-metoxi-6-metilflavanona; 3 -formil-3,4 ,6 -triidroxi-2 - metoxi-5 -metilchalcona e (2 -metoxi-3 -formil-4 ,6 -dihidroxi-5 -metilfenil)-[3 - (dimetilbut-6 -enil)-7-fenil-(3-hidroxi)-ciclohex-2 -enil]-metil-9-ona. Os extratos e algumas fases e substâncias isoladas foram disponibilizadas para a investigação da atividade antimicrobiana, hemolítica e moduladora da resistência à drogas antibacterianas.

This thesis describes a procedure used to synthesize a-(p-Aminophenylsulfonyl)-p-methylacetophenone, a-(p-aminophenylsulfonyl)-p-bromoacetophenone, and a-(p-aminophenylsulfonyl)-p-methoxyacetophenone for study as possible new anti-tubercular agents.

Les composés organiques présentant une chiralité portée par un atome de phosphore sont appelés composés P-chiraux, P-chirogéniques ou P-stéréogéniques. Ces composés trouvent des nombreuses applications dans l’industrie agrochimique et pharmaceutique, en tant qu’outils de coordination, mais surtout en catalyse organométallique asymétrique en tant que ligands privilégiés (Prix Nobel pour W. S. Knowles en 2001). Cependant, la synthèse de composés P-chiraux reste un défi majeur et les méthodes actuellement utilisées sont souvent difficiles à mettre en oeuvre et multi-étapes. Au cours de cette thèse nous nous sommes intéressés au développement d’une méthodologie efficace et inédite pour la synthèse de composés P-stéréogeniques. Notre approche est basée sur la réaction d’Atherton-Todd et implique le dédoublement cinétique dynamique lors d’un couplage entre un phénol portant un auxiliaire de chiralité, ie. le sulfoxyde, et un H-phosphinate racémique. De plus, la post-functionalisation des composés diastéréomériques P-chiraux ainsi obtenus est possible dans des conditions douces, permettant ainsi d’accéder à un large panel de composés P-stéréogeniques. Ainsi, cette nouvelle méthodologie permet de synthétiser, via un couplage O-P diastéréosélectif, des précurseurs originaux de composés P-chiraux variés. / Organic compounds having chirality on phosphorous atom, are called P-stereogenic, P-chirogenic or P-chiral compounds. These compounds are widely used in agrochemistry, pharmacy, coordination chemistry and in organometallic asymmetric catalysis, as one of the most important classes of chiral ligands (Nobel Prize 2001; W. S. Knowles). However, access to these P-stereogenic compounds, is challenging due to the complex, tedious and multi-steps synthetic methodologies. Herein, we report a highly efficient novel methodology to access P-stereogenic compounds, which often involves dynamic kinetic resolution (DKR) under modified Atherton-Todd reaction conditions, using a racemic H-phosphinate and an enantiopure phenol bearing a chiral sulfoxide moiety. Furthermore, the newly obtained O-P coupling product can potentially be post-functionalised under mild conditions to obtain various original P-stereogenic scaffolds. Thus, these O-P coupling products can be considered as highly potential precursors to access a variety of original P-stereogenic molecules.

Theses (M.S.)--University of Wisconsin, 1962. / Description based on print version record.

The cytochrome P450 enzymes (CYPs) are very attractive biocatalysts because of their ability to regio- and stereo-selectively catalyze the insertion of a single atom of molecular oxygen into inactivated C-H bonds. There are many drawbacks, however, limiting the use of these enzymes in organic synthesis, including the need for expensive cofactors, low stability, and low tolerance to organic solvents. The goal of this thesis was to overcome some of these drawbacks for human CYP2D6. This isoform was selected because of its broad substrate promiscuity and high importance in drug metabolism. / We have tested inexpensive chemicals to replace the natural cofactors of CYP2D6, NADPH and cytochrome P450 reductase (CPR). The results showed that cumene hydroperoxide and tert-butyl hydroperoxide can successfully substitute CPR and NAD(P)H with retained regio- and stereo-selectivity. Moreover, with these surrogates, product formation and initial rates are increased by as much as two fold compared to the use of the natural cofactors. / It is widely accepted that even small proportions of organic solvents in the buffer can deactivate most enzymes including P450s. Our studies on the biocatalysis of CYP2D6 in organic solvent/buffer emulsions showed that under the optimized conditions, as much as 76% of the enzyme activity was retained. Product formation in biphasic solvent systems is comparable whether the natural redox partner and cofactor are used, or a surrogate. In addition, a correlation was observed between the log P and the suitability of a solvent for enzymatic activity, with higher log P resulting in higher enzymatic activity. These results were obtained with dextromethorphan (DXM), a water soluble substrate. A very hydrophobic substrate, 7-benzyloxy-4-N,N-diethylaminomethyl-coumarin (BDAC), was also tested successfully to demonstrate the utility of this method. / Lyophilization is usually required to remove water before using enzymes in nearly anhydrous solvents. This physical process is harmful to P450 enzyme activity. We therefore tested numerous sugars as lyoprotectant during lyophilization. Addition of trehalose or sucrose before lyophilization allowed the retention of 80% of the CYP2D6 activity, compared to 40% remaining activity in its absence. CYP2D6 co-lyophilized with trehalose was next tested in selected hydrophobic organic solvents in the absence of water. The enzymatic activity was found to strongly depend on the hydrophobicity of the solvent. Interestingly, the enzyme showed higher catalytic ability in n-decane or n-dodecane than in the standard buffer. This was unexpected considering that the activity of most enzymes was reported to decrease to 10% or less in nearly anhydrous organic solvents. / The last objective of this thesis was to improve the stability and/or activity of CYP2D6. Use of DNA self-assemblies to encapsulate P450 enzymes was envisaged to potentially increase their stability. Indeed, DNA assemblies have many advantages compared to traditional solid supports reported for enzymes. Our preliminary results showed that CYP2D6 templated the formation of cyclic DNA dimeric and tetrameric over polymeric self-assemblies. Characterization of the CYP2D6 activity in the presence of the DNA self-assemblies revealed no loss of activity or stability.

No description available.

This thesis examines the properties of spatial (i.e., locational and directional) Ps within the minimalist framework (Chomsky 1995,1998,1999), which has put an ultimate emphasis on economy in terms of derivation and representation. The principal goals of this thesis are (i) to investigate how the syntax of such nature derives PPs in accordance with the properties of Ps and (ii) to show how the internal PP structure interacts with the external syntax of PP. Chomsky's minimalist framework assumes two syntactic operations, i.e.. Merge and Move, and two different types of outcome of the operations, depending on the properties of lexical items involved in each operation executed. One outcome results from a merger of two items, of which one selects the other. The other results from a merger of two items, neither of which selects the other. I propose that there are three heads involved in deriving a layered PP structure: functional p, lexical P and locative N. This analysis is shown to be empirically supported from languages such as Dutch, English, Hungarian, Japanese and K'ekchi. I also claim that there are also intransitive Ps that adjoin to either or pP. The internal structure of PP interacts with its external syntax. One apparent area of grammar that shows desirable consequences for the layered PP analysis is P-to-V incorporation. For instance, the incorporability versus the unincorporability of Ps in Dutch can be accounted for by the principle (i.e.. Minimal Link Condition) that forbids skipping over an intermediate head, thus supporting the layered structure of PP. Another area offering support is locative inversion: the presence versus the absence of locative N head in PP can account for a contrast observed in locative inversion facts. Provided that an EPP-feature of T is category-specific, a contrast between PPs that can undergo movement to [Spec, T] and those that cannot stems from their respective internal structures.

Thèse (Ph. D.)--Université Laval, 2007 . / Bibliogr.: f. 232-239. Publié aussi en version électronique dans la Collection Mémoires et thèses électroniques.

Akademisk avhandling--Stockholms bögskola. / Extra t.p., with thesis statement, inserted. "Rättelser": leaf inserted. Bibliography: p. [267]-274.