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Molecular Docking and Molecular Dynamic Studies of Semi-Synthetic Piperidine Alkaloids as Acetylcholinesterase Inhibitors

Danuello, Amanda; Romeiro, Nelilma C.; Giesel, Guilherme M.; Pivatto, Marcos; Viegas, Claudio; Verli, Hugo; Barreiro, Eliezer J.; Fraga, Carlos A. M.; Castro, Newton G.; Bolzani, Vanderlan da Silva
Fonte: Soc Brasileira Quimica Publicador: Soc Brasileira Quimica
Tipo: Artigo de Revista Científica Formato: 163-U505
ENG
Relevância na Pesquisa
36.41%
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); Processo FAPESP: 03/02176-7; The mixture of semi-synthetic derivatives (-)-3-O-acetyl-cassine hydrochloride and (-)-3-O-acetyl-spectaline hydrochloride, prepared from the mixture of natural alkaloids (-)-cassine and (-)-spectaline (4:1) isolated from Senna spectabilis, has been shown to be a potent acetylcholinesterase (AChE) inhibitor, thereby prompting further molecular studies. In this sense, docking and dynamic molecular studies were carried out in this work, aiming to acquire a deeper understanding about all the structural aspects of molecules (-)-3-O-acetyl-cassine and (-)-3-O-acetyl-spectaline hydrochlorides, which differ with respect to their AChE inhibitory potentials. Both molecules establish important interactions with the peripheral anionic site within the catalytic gorge of Torpedo californica AChE. However, only the major compound (-)-3-O-acetyl-cassine hydrochloride significantly interacts with the catalytic triad. Explicit-solvent molecular dynamic simulations were conducted in order to gain better understanding about the hypothetical interactions taking place between the semi-synthetic alkaloid molecules (-)-3-O-acetyl-cassine and (-)-3-O-acetyl-spectaline hydrochlorides and AChE. The data obtained in this study indicated that (-)-3-O-acetyl-cassine hydrochloride is the most potent inhibitor of AChE possibly due to the favorable interactions of this molecule with the target protein...

Antinociceptive profile of 2,3,6-trisubstituted piperidine alkaloids: 3-O-acetyl-spectaline and semi-synthetic derivatives of (-)-spectaline

Viegas, Claudio; Alexandre-Moreira, Magna Suzana; Marissour Fraga, Carlos Alberto; Barreiro, Eliezer Jesus; Bolzani, Vanderlan da Silva; Palhares de Miranda, Ana Luisa
Fonte: Pharmaceutical Soc Japan Publicador: Pharmaceutical Soc Japan
Tipo: Artigo de Revista Científica Formato: 407-412
ENG
Relevância na Pesquisa
36.74%
In early studies, we have reported the antinociceptive profile of (-)-spectaline, a piperidine alkaloid from Cassia spectabilis. The present study describes the synthesis, the antinociceptive and anti-inflammatory activities of a series of 2,3,6-trialkyl-piperidine alkaloids: the natural (-)-3-O-acetyl-spectaline (LASSBio-755) and ten semi-synthetic spectaline derivatives. Structure-activity relationship (SARs) studies were performed. The structures of all synthesized derivatives were confirmed by means of nuclear magnetic resonance. Compounds were evaluated for their analgesic (acetic acid-induced mouse abdominal constrictions, hot-plate test, formalin-induced pain test) and some of them for the anti-inflammatory activities (carrageenan-induced rat paw edema test). The pharmacological results showed that several of the new compounds given orally at a dose of 100 mu mol/kg significantly inhibited the acetic acid-induced abdominal constrictions, but they were less active than (-)-spectaline. LASSBio-755 and LASSBio-776 were the most actives with 37% and 31.7% of inhibition. In the formalin-induced pain only LASSBio-776 was able to inhibit by 34.4% the paw licking response of the inflammatory phase, (-)-spectaline and LASSBio-755 did show any activity. In the carrageenan-induced rat paw edema...

Antimalarial activity of piperidine alkaloids from Senna spectabilis and semisynthetic derivatives

Pivatto, Marcos; Baccini, Luciene R.; Sharma, Abhinay; Nakabashi, Myna; Danuello, Amanda; Viegas Júnior, Claudio; Garcia, Celia R. S.; Bolzani, Vanderlan S.
Fonte: Sociedade Brasileira de Química Publicador: Sociedade Brasileira de Química
Tipo: Artigo de Revista Científica Formato: 1900-1906
ENG
Relevância na Pesquisa
36.74%
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); In our continuing work looking for new anti-infective lead compounds from Brazilian biomes, the two known piperidine alkaloids ( - )-cassine and ( - )-spectaline were isolated from the flowers of Senna spectabilis (syn. Cassia spectabilis). Their structures were elucidated using a combination of spectroscopic and spectrometric data analysis. Further, these compounds were acetylated yielding the derivatives ( - )-3-O-acetylcassine and ( - )-3-O-acetylspectaline. All compounds were screened against P. falciparum-infected red blood cells (RBC) in culture, aiming to identify antimalarial prototypes. Among all compounds screened, the first two alkaloids (IC50 1.82 µM and IC50 2.76 µM) were more effective than the derivatives (IC50 24.47 µM and IC50 25.14 µM) in comparison to the standard compound chloroquine (IC50 0.30 µM). These data show that piperidine alkaloids constitute a class of natural products that feature a broad spectrum of biological activities, and are, therefore, important templates for drug design, including antimalarial.; Dando continuidade as pesquisas de identificação de metabólitos secundários com propriedades anti-infecciosas potenciais a partir de espécies de plantas dos biomas brasileiros...

Adição de nucleofilos de carbono a ions N-aciliminio substituidos

Adriano Otavio Maldaner
Fonte: Biblioteca Digital da Unicamp Publicador: Biblioteca Digital da Unicamp
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 01/11/1999 PT
Relevância na Pesquisa
26.62%
O presente trabalho descreve os estudos de adição de nucleófilos de carbono a íons N-acilimínio substituídos e a utilização desta metodologia na obtenção estereosseletiva de sistemas piperidínicos, quinolizidínicos, indolizidínicos e decaidroquinolínicos. Para tal obteve-se N-Boc-2-piperidinonas 2.18 e 2.19 e as N-Boc-2-pirrolidinonas 2.20 e 2.21, substituídas na posição vizinha ao nitrogênio do anel, a partir da adição de reagentes de Grignard à glutarimida e succinimida, respectivamente, redução da hidroxilactama formada e proteção do nitrogênio na forma do carbamato terc-butílico. Estas lactamas foram utilizadas como substratos em um estudo sistemático de alquilação, levando às N-Boc-2-piperidinonas 3,6-dissubstituídas 2.22-2.24 e 2.28 e às N-Boc-2-pirrolidinonas 2.34, 2.35, 2.38-2.43 em rendimentos de 45-83%, após formação dos respectivos enolatos de lítio e captura com os eletrófilos iodeto de metila, brometo de alila e brometo de benzila. Foram obtidas altas seletividades (>96:6) em favor dos produtos trans-dissubstituídos em todos os sistemas e somente no caso das alquilações de sistemas pirrolidínicos com iodeto de metila foram obtidas misturas com os produtos cis-dissubstituídos. A redução da carbonila endocíclica das lactamas dissubstituídas...

New enamine derivatives of lapachol and biological activity

OLIVEIRA,MAILCAR F.; LEMOS,TELMA L.G.; MATTOS,MARCOS C. DE; SEGUNDO,TACIANA A.; SANTIAGO,GILVANDETE M.P.; BRAZ-FILHO,RAIMUNDO
Fonte: Academia Brasileira de Ciências Publicador: Academia Brasileira de Ciências
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/06/2002 EN
Relevância na Pesquisa
36.25%
A convenient synthesis of the new enamine derivatives 2-(4-morpholinyl)-3-(3-methyl-2-butenyl)-1,4-naphthalenedione, 2-(1-piperidinyl)-3-(3-methyl-2-butenyl)-1,4-naphtalenedione and 2-(1-pyrrolidinyl)-3-(3-methyl-2-butenyl)-1,4-naphthalenedione was carried out from natural 2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthalenedione (lapachol) and morpholine, piperidine and pyrrolidine. The structures of the products were established mainly by NMR analysis, including 2D experiments. Biological activities of these products were evaluated against Artemia salina, Aedes aegypti and cytotoxicity using A549 human breast cells.

Molecular docking and molecular dynamic studies of semi-synthetic piperidine alkaloids as acetylcholinesterase inhibitors

Danuello,Amanda; Romeiro,Nelilma C.; Giesel,Guilherme M.; Pivatto,Marcos; Viegas Jr.,Claudio; Verli,Hugo; Barreiro,Eliezer J.; Fraga,Carlos A. M.; Castro,Newton G.; Bolzani,Vanderlan S.
Fonte: Sociedade Brasileira de Química Publicador: Sociedade Brasileira de Química
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2012 EN
Relevância na Pesquisa
36.41%
The mixture of semi-synthetic derivatives (-)-3-O-acetyl-cassine hydrochloride and (-)-3-O-acetyl-spectaline hydrochloride, prepared from the mixture of natural alkaloids (-)-cassine and (-)-spectaline (4:1) isolated from Senna spectabilis, has been shown to be a potent acetylcholinesterase (AChE) inhibitor, thereby prompting further molecular studies. In this sense, docking and dynamic molecular studies were carried out in this work, aiming to acquire a deeper understanding about all the structural aspects of molecules (-)-3-O-acetyl-cassine and (-)-3-O-acetyl-spectaline hydrochlorides, which differ with respect to their AChE inhibitory potentials. Both molecules establish important interactions with the peripheral anionic site within the catalytic gorge of Torpedo californica AChE. However, only the major compound (-)-3-O-acetyl-cassine hydrochloride significantly interacts with the catalytic triad. Explicit-solvent molecular dynamic simulations were conducted in order to gain better understanding about the hypothetical interactions taking place between the semi-synthetic alkaloid molecules (-)-3-O-acetyl-cassine and (-)-3-O-acetyl-spectaline hydrochlorides and AChE. The data obtained in this study indicated that (-)-3-O-acetyl-cassine hydrochloride is the most potent inhibitor of AChE possibly due to the favorable interactions of this molecule with the target protein...

Antimalarial activity of piperidine alkaloids from Senna spectabilis and semisynthetic derivatives

Pivatto,Marcos; Baccini,Luciene R.; Sharma,Abhinay; Nakabashi,Myna; Danuello,Amanda; Viegas Júnior,Claudio; Garcia,Celia R. S.; Bolzani,Vanderlan S.
Fonte: Sociedade Brasileira de Química Publicador: Sociedade Brasileira de Química
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/10/2014 EN
Relevância na Pesquisa
36.74%
In our continuing work looking for new anti-infective lead compounds from Brazilian biomes, the two known piperidine alkaloids ( - )-cassine and ( - )-spectaline were isolated from the flowers of Senna spectabilis (syn. Cassia spectabilis). Their structures were elucidated using a combination of spectroscopic and spectrometric data analysis. Further, these compounds were acetylated yielding the derivatives ( - )-3-O-acetylcassine and ( - )-3-O-acetylspectaline. All compounds were screened against P. falciparum-infected red blood cells (RBC) in culture, aiming to identify antimalarial prototypes. Among all compounds screened, the first two alkaloids (IC50 1.82 µM and IC50 2.76 µM) were more effective than the derivatives (IC50 24.47 µM and IC50 25.14 µM) in comparison to the standard compound chloroquine (IC50 0.30 µM). These data show that piperidine alkaloids constitute a class of natural products that feature a broad spectrum of biological activities, and are, therefore, important templates for drug design, including antimalarial.

Synthesis and SAR of 3,5-diamino-piperidine derivatives: Novel antibacterial translation inhibitors as aminoglycoside mimetics

Zhou, Yuefen; Gregor, Vlad E.; Ayida, Benjamin K.; Winters, Geoffrey C.; Sun, Zhongxiang; Murphy, Douglas; Haley, Greg; Bailey, Dwight; Froelich, Jamie M.; Fish, Sarah; Webber, Stephen E.; Hermann, Thomas; Wall, Daniel
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
46.41%
Aminoglycoside antibiotics target an internal RNA loop within the bacterial ribosomal decoding site. Here, we described the synthesis and SAR of novel 3,5-diamino-piperidine derivatives as aminoglycoside mimetics, and show they act as inhibitors of bacterial translation and growth.

Binding and structure-activity-relation of benzo[f]isoquinoline- and norcodeinone-derivatives at mu-opioid receptors in the rat cerebral cortex.

Freissmuth, M.; Beindl, W.; Kratzel, M.
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Publicado em /12/1993 EN
Relevância na Pesquisa
26.61%
1. We have probed the ligand binding site of the mu-opioid receptor using a series of isoquinoline- and norcodeinone-derivatives; in these morphine- and codeine-analogues, the position of the piperidine-nitrogen as well as its mobility is altered relative to that found in morphine. 2. The mu-receptor in rat cortical membranes was labelled with [3H]-naloxone and competition experiments were carried out in the absence and presence of Gpp(NH)p and NaCl: conditions, which are associated with affinity shifts for agonists whilst antagonist affinity remains unaffected. Moving the piperidine-nitrogen closer to the phenolic ring or reducing its mobility by incorporation into an additional ring drastically decreases the affinity. 3. In contrast, we find that the piperidine-nitrogen in a distal position is well tolerated provided that additional structural criteria, in particular a phenolic hydroxyl-group and a 6 carbon ring corresponding to ring C in morphine, are met. This assumption was verified by the synthesis of WB4/PH (4aR, 10bS, 11R)-10, 11-epoxy-1, 2, 3, 4, 5, 6-hexahydro-9-hydroxy-3-methyl-4a,10b-butano- benzo[f]isochinolin-12-on(10). This compound is an agonist with an affinity comparable to that of morphine. 4. We therefore conclude that both the mobility of the piperidine nitrogen of the ligand and of its counterpart anionic site in the ligand binding pocket of the mu-opioid receptor (presumably aspartic acid) are important determinants for fruitful interaction. The mobility of the anionic site is restricted in one direction but is sufficient to bridge the 2A distance that exists between the position of the nitrogen in morphine and WB4/PH.

Further structural optimization of cis-(6-benzhydryl-piperidin-3-yl)-benzylamine and 1,4-diazabicyclo[3.3.1]nonane derivatives by introducing an exocyclic hydroxyl group: Interaction with dopamine, serotonin and norepinephrine transporters

Mishra, Manoj; Kolhatkar, Rohit; Zhen, Juan; Parrington, Ingrid; Reith, Maarten E. A.; Dutta, Aloke K.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
36.59%
Our earlier effort to develop constrained analogues of flexible piperidine analogs for monoamine transporters led to the development of a series of 3,6-disubstituted piperidine derivatives, and a series of 4,8-disubstituted 1,4-diazabicyclo[3.3.1]nonane derivatives. In further structure-activity relationship (SAR) studies on these constrained derivatives, several novel analogues were developed where an exocyclic hydroxyl group was introduced on the N-alkyl-aryl side chain. All synthesized derivatives were tested for their affinities for the dopamine transporter (DAT), serotonin (5-HT) transporter (SERT), and norepinephrine transporter (NET) in the brain by measuring their potency in inhibiting the uptake of [3H]DA, [3H]5-HT, and [3H]NE, respectively. Compounds were also tested for their binding potency at the DAT by their ability to inhibit binding of [3H]WIN 35,428. The results indicated that position of the hydroxyl group on the N-alkyl side chain is important along with the length of the side chain. In general, hydroxyl derivatives derived from more constrained bicyclic diamines exhibited greater selectivity for interaction with DAT compared to the corresponding 3,6-disubstituted diamines. In the current series of molecules, compound 11b with N-propyl side chain with the hydroxyl group attached in the benzylic position was the most potent and selective for DAT (Ki = 8.63 nM; SERT/DAT = 172 and NET/DAT = 48.4).

Quantitative analysis of penicillins in porcine tissues, milk and animal feed using derivatisation with piperidine and stable isotope dilution liquid chromatography tandem mass spectrometry

van Holthoon, Frédérique; Mulder, Patrick P. J.; van Bennekom, Eric O.; Heskamp, Henri; Zuidema, Tina; van Rhijn, Hans (J.) A.
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
36.74%
Penicillins are used universally in both human and veterinary medicine. The European Union (EU) has established maximum residue levels (MRLs) for most ß-lactam antibiotics in milk and animal tissues and included them in the National Residue Monitoring Programs. In this study, a novel method is described for the determination and confirmation of eight penicillins in porcine tissues, milk and animal feed by liquid chromatography–tandem mass spectrometry (LC–MS/MS). To prevent degradation of penicillin residues during workup, a derivatisation procedure was developed, by which penicillins were converted to stable piperidine derivatives. Deuterated piperidine derivatives were synthesised for all relevant penicillins, enabling the use of isotope dilution for accurate quantification. Penicillin residues were derivatised in the crude extract with piperidine and isolated using solid-phase extraction. The penicillin piperidine derivatives were determined by LC–MS/MS. The method was validated at the current MRLs, which range from 25–300 µg kg−1 in muscle and kidney to 4–30 µg kg−1 in milk as well as at the target value of 100 µg kg−1 chosen for animal feed, according to the EU requirements for a quantitative confirmatory method. Accuracy ranged from 94–113% (muscle)...

Design, Synthesis, and Pharmacological Evaluation of Haloperidol Derivatives as Novel Potent Calcium Channel Blockers with Vasodilator Activity

Chen, Yicun; Zheng, Jinhong; Zheng, Fuchun; Wang, Jinzhi; Zhang, Yanmei; Gao, Fenfei; Huang, Zhanqin; Shi, Ganggang
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 16/11/2011 EN
Relevância na Pesquisa
26.41%
Several haloperidol derivatives with a piperidine scaffold that was decorated at the nitrogen atom with different alkyl, benzyl, or substituted benzyl moieties were synthesized at our laboratory to establish a library of compounds with vasodilator activity. Compounds were screened for vasodilatory activity on isolated thoracic aorta rings from rats, and their quantitative structure–activity relationships (QSAR) were examined. Based on the result of QSAR, N-4-tert-butyl benzyl haloperidol chloride (16c) was synthesized and showed the most potent vasodilatory activity of all designed compounds. 16c dose-dependently inhibited the contraction caused by the influx of extracellular Ca2+ in isolated thoracic aorta rings from rats. It concentration-dependently attenuated the calcium channel current and extracellular Ca2+ influx, without affecting the intracellular Ca2+ mobilization, in vascular smooth muscle cells from rats. 16c, possessing the N-4-tert-butyl benzyl piperidine structure, as a novel calcium antagonist, may be effective as a calcium channel blocker in cardiovascular disease.

A case of levocetirizine-induced fixed drug eruption and cross-reaction with piperazine derivatives

Kim, Mi-Yeong; Jo, Eun-Jung; Chang, Yoon-Seok; Cho, Sang-Heon; Min, Kyung-Up; Kim, Sae-Hoon
Fonte: Asia Pacific Association of Allergy, Asthma and Clinical Immunology Publicador: Asia Pacific Association of Allergy, Asthma and Clinical Immunology
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
36.57%
Fixed drug eruption is an uncommon adverse drug reaction caused by delayed cell-mediated hypersensitivity. Levocetirizine is an active (R)-enatiomer of cetirizine and there have been a few reports of fixed drug eruption related to these antihistamines. We experienced a case of levocetirizine-induced fixed drug eruption and cross-reaction with other piperazine derivatives confirmed by patch test. A 73-year-old female patient presented with recurrent generalized itching, cutaneous bullae formation, rash and multiple pigmentation at fixed sites after taking drugs for common cold. She took bepotastine besilate (Talion®) and levocetirizine (Xyzal®) as antihistamine. She took acetaminophen, pseudoephedrine 60 mg / triprolidine 2.5 mg (Actifed®), dihydrocodeinebitartrate 5 mg / di-methylephedrine hydrochloride 17.5 mg / chlorpheniramine maleate 1.5 mg / guaifenesin 50 mg (Codening®) and aluminium hydroxide 200 mg / magnesium carbonate 120 mg (Antad®) at the same time. Patch test was done with suspected drugs and the result was positive with levocetirizine. We additionally performed patch test for other antihistamines such as cetirizine, hydroxyzine, fexofenadine and loratadine. Piperazine derivatives (cetirizine and hydroxyzine) were positive...

The Influence of pH and Temperature on the Stability of N-[(Piperidine)methylene]daunorubicin Hydrochloride and a Comparison of the Stability of Daunorubicin and Its Four New Amidine Derivatives in Aqueous Solutions

Piekarski, Mikołaj; Dołhań, Agnieszka; Cielecka-Piontek, Judyta; Zalewski, Przemysław; Kycler, Witold; Kaczmarek, Aleksandra; Firlej, Artur; Oszczapowicz, Irena; Jelińska, Anna
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
Publicado em 06/02/2014 EN
Relevância na Pesquisa
26.54%
The influence of pH and temperature on the stability of N-[(piperidine)methylene]daunorubicin hydrochloride (PPD) was investigated. Degradation was studied using an HPLC method. Specific acid-base catalysis of PPD involves hydrolysis of protonated molecules of PPD catalyzed by hydrogen ions and spontaneous hydrolysis under the influence of water zwitterions, unprotonated molecules, and monoanions of PPD. The thermodynamic parameters of these reactions, energy, enthalpy, and entropy, were calculated. Also, the stability of daunorubicin and its new amidine derivatives (piperidine, morpholine, pyrrolidine, and hexahydroazepin-1-yl) in aqueous solutions was compared and discussed.

Synthesis, Spectral Analysis, In Vitro Microbiological Evaluation, and Molecular Docking Studies of Some Novel 1-(1-Aryl-1H-tetrazol-5-yl)-2-(piperidin-1-yl)ethanone Derivatives

Elavarasan, Thangasamy; Bhakiaraj, Durairaj Peter; Gopalakrishnan, Mannathusamy
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
Publicado em 06/05/2014 EN
Relevância na Pesquisa
36.54%
A new series of novel heterocyclic compounds containing both tetrazoles and piperidine nuclei together, namely, 1-(1-aryl-1H-tetrazol-5-yl)-2-(piperidin-1-yl)ethanone (22–28), were synthesized by the treatment of the respective 2-chloro-1-(1-aryl-1H-tetrazol-5-yl)ethanone (15–21) with piperidine in acetonitrile for 6 h. A series of novel tetrazole substituted piperidine derivatives were synthesized and evaluated for their antimicrobial activity using serial dilution method. The structures of the synthesized compounds were characterized by IR, 1H NMR, 13C NMR, mass spectral data, and elemental analysis. Evaluation of antimicrobial activity shows that several compounds exhibit good activity when compared with the reference drug candidates and thus could be promising new lead molecules.

Synthèse stéréosélective de dérivés pipéridines polysubstitués par fragmentation de Grob

St-Onge, Miguel
Fonte: Université de Montréal Publicador: Université de Montréal
Tipo: Thèse ou Mémoire numérique / Electronic Thesis or Dissertation
FR
Relevância na Pesquisa
46.41%
Dans ce mémoire, il sera question de la formation de dérivés pipéridines en utilisant la fragmentation de Grob. Tout d’abord, une introduction sur les alcaloïdes ainsi que sur l’expertise du groupe Charette associée à leur formation démontrera l’importance de ces composés dans le domaine de la chimie organique. Cela sera suivi par un résumé de la fragmentation de Grob incluant les conditions de réactions utilisées, l’importance de la structure de la molécule initiale, les prérequis stéréoélectroniques ainsi que les modifications qui y ont été apportées. Le chapitre 2 sera dédié au développement de la méthodologie c’est-à-dire, à l’optimisation de tous les paramètres jouant un rôle dans la fragmentation de Grob. Par la suite, l’étendue de la réaction ainsi que des explications sur la régiosélectivité et la diastéréosélectivité de la réaction seront fournies. La méthodologie peut être exploitée dans un contexte de synthèse qui sera démontré dans le chapitre 3. De plus, elle servira pour une étude mécanistique qui est encore d’actualité à partir du concept d’effet frangomérique. Finalement, quelques projets futurs, notamment des améliorations possibles de la méthodologie...

The addition of allyltrimethylsilane to cyclic N-acyliminium ions derived from(S)-(+)-mandelic acid and cyclohexyl-based chiral auxiliaries

D'Oca,Marcelo G. M.; Pilli,Ronaldo A.; Pardini,Vera L.; Curi,Denise; Comninos,Francisco C. M.
Fonte: Sociedade Brasileira de Química Publicador: Sociedade Brasileira de Química
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/08/2001 EN
Relevância na Pesquisa
36.17%
The TiCl4- promoted addition of allyltrimethylsilane to chiral 5- and 6-membered N-acyliminium ions employing (S)-(+)-mandelic acid, (1R,2S)-trans-2-phenyl-1-cyclohexanol and (1R,2S,5R)-8-phenylmenthol derivatives as chiral auxiliaries occurred with low to moderate diastereoisomeric ratios (1:1-6:1) to afford 2-substituted amides and carbamates in good yields. The best diastereoselection was observed with (1R,2S,5R)-8-phenylmenthol as the chiral auxiliary. The 2-substituted amides and carbamates were converted to the corresponding alkaloids (S)- and (R)-propyl pyrrolidine and coniine with efficient recovery of the chiral auxiliaries.

The addition of allyltrimethylsilane to cyclic n-acyliminium Ions derived from(S)-(+)-mandelic acid and cyclohexyl-based chiral auxiliaries

D'Oca, Marcelo Gonçalves Montes; Pilli, Ronaldo Aloise; Pardini, Vera Lucia; Curi, Denise; Comninos, Francisco Carlos Mikula
Fonte: Universidade Federal do Rio Grande Publicador: Universidade Federal do Rio Grande
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
36.17%
A adição de aliltrimetilsilano, promovida por TiCl4, a íons N-aciliminios cíclicos de 5- e 6-membros derivados do ácido (S)-(+)-mandélico, (1R,2S)-trans-2-fenil-1-cicloexanol e (1R,2S,5R)-8-fenilmentol ocorreu com baixas a moderadas razões diastereoisoméricas (1:1-6:1) e forneceuas respectivas amidas e carbamatos em bons rendimentos. A melhor diastereosseleção facial foiobservada com o uso de (1R,2S,5R)-8-fenilmentol como auxiliar quiral. As amidas e carbamatos2-substituídos foram convertidos nos alcalóides (S)- e (R)-propil pirrolidina e coniina com eficienterecuperação dos auxiliares quirais; The TiCl4- promoted addition of allyltrimethylsilane to chiral 5- and 6-memberedN-acyliminium ions employing (S)-(+)-mandelic acid, (1R,2S)-trans-2-phenyl-1-cyclohexanol and (1R,2S,5R)-8-phenylmenthol derivatives as chiral auxiliaries occurredwith low to moderate diastereoisomeric ratios (1:1-6:1) to afford 2-substituted amides andcarbamates in good yields. The best diastereoselection was observed with (1R,2S,5R)-8-phenylmenthol as the chiral auxiliary. The 2-substituted amides and carbamates wereconverted to the corresponding alkaloids (S)- and (R)-propyl pyrrolidine and coniine withefficient recovery of the chiral auxiliaries

The addition of allyltrimethylsilane to cyclic N-acyliminium ions derived from (S)-(+)-mandelic acid and cyclohexyl-based chiral auxiliaries

D'Oca, Marcelo Gonçalves Montes; Pilli, Ronaldo Aloise; Pardini, Vera Lucia; Curi, Denise; Comninos, João Francisco Corrêa
Fonte: Sociedade Brasileira de Química Publicador: Sociedade Brasileira de Química
Tipo: Artigo de Revista Científica
ENG
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A adição de aliltrimetilsilano, promovida por TiCl4, a íons N-aciliminios cíclicos de 5- e 6- membros derivados do ácido (S)-(+)-mandélico, (1R,2S)-trans-2-fenil-1-cicloexanol e (1R,2S,5R)- 8-fenilmentol ocorreu com baixas a moderadas razões diastereoisoméricas (1:1-6:1) e forneceu as respectivas amidas e carbamatos em bons rendimentos. A melhor diastereosseleção facial foi observada com o uso de (1R,2S,5R)-8-fenilmentol como auxiliar quiral. As amidas e carbamatos 2-substituídos foram convertidos nos alcalóides (S)- e (R)-propil pirrolidina e coniina com eficiente recuperação dos auxiliares quirais.; The TiCl4 - promoted addition of allyltrimethylsilane to chiral 5- and 6-membered N-acyliminium ions employing (S)-(+)-mandelic acid, (1R,2S)-trans-2-phenyl-1- cyclohexanol and (1R,2S,5R)-8-phenylmenthol derivatives as chiral auxiliaries occurred with low to moderate diastereoisomeric ratios (1:1-6:1) to afford 2-substituted amides and carbamates in good yields. The best diastereoselection was observed with (1R,2S,5R)-8- phenylmenthol as the chiral auxiliary. The 2-substituted amides and carbamates were converted to the corresponding alkaloids (S)- and (R)-propyl pyrrolidine and coniine with efficient recovery of the chiral auxiliaries.

Solution-phase combinatorial synthesis; Peptide derivatives of ethyl p-aminobenzoate

Scuderi, Andrea
Fonte: Rochester Instituto de Tecnologia Publicador: Rochester Instituto de Tecnologia
Tipo: Tese de Doutorado
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The need to find more efficient and cost-effective methods of drug development has led pharmaceutical companies to examine combinatorial means of synthesis. The ability to carry out parallel synthesis by the hundreds of compounds is rapidly advancing synthetic, analytical, and biological research. In this thesis project, peptide derivatives of ethyl paminobenzoate were synthesized via solution phase combinatorial techniques. A total of 27 tri-peptide analogs were produced, using a polymer-supported carbodiimide resin as the coupling agent. The structures of all products and intermediates were confirmed by LC-MS. Two methods were used for sequential deprotection of these analogs. The traditional method using the mild base, piperidine, was used as well as a polymersupported thiophenol method. Upon comparison of both methods, we concluded that the piperidine deprotection afforded a higher yield of the desired unprotected peptide.