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An Efficient Synthesis of £^-Substituted £\,£]-Unsaturated £_-Lactams. Formal Synthesis of (¡Ó)-Protoemetinol.Huang, Chang-Gin 18 June 2002 (has links)
£^-Substituted £\,£]-unsaturated £_-lactams was synthesized from £\-sulfinyl acetamides in three steps.
Formal synthesis of (¡Ó)-Protoemetinol was also reported.
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Regioselective Reduction of N-Alkyl-3-sulfonyl Glutarimides and the Applications in Pharmaceuticals and Natural Product SynthesisChang, Bo-Rui 19 December 2002 (has links)
A formal [3+3] cycloaddition strategy to substituted glutarimides was studied. N-Alkyl-sulfonylacetamides and various a,b-unsaturated esters were used as starting materials. Regioselective reduction of N-alkyl-3-sulfonyl glutarimides and the applications in pharmaceuticals and natural product synthesis
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Synthesis and Bioactivity Investigation of Bridged Bicyclic Compounds and a Mechanistic Investigation of a Propargyl Hydrazine Cycloaddition Catalyzed by an Ammonium SaltUnknown Date (has links)
We report the development of a general route to the synthesis of [4.3.1], [3.3.1],
an especially [3.2.1] bicyclic compounds structurally related to vitisinol D, a natural
product. This allows for diastereoselective synthesis of bicyclic compounds with
five adjacent chiral centers. This route was employed in a preliminary SAR
investigation into the neuroprotectant effect of small molecules in an in vivo
experiment measuring the degree of restorative effect of synaptic transmission in
the neuromuscular junction of Drosophila melanogaster larvae under acute
oxidative stress. One of the compounds exhibited intriguing potential as a
neuroprotectant and outperformed resveratrol in restoring synaptic function under
oxidative stress. The hypothesis that bridged bicyclic compounds may hold promise as drug scaffolds due to their conformational rigidity and ability to orient
functional appendages in unique orientations is developed.
The second focus is a mechanistic investigation into a tetrabutylammoniumcatalyzed
cycloaddition as evidence of a novel ammonium-alkyne interaction. A
carbamate nitrogen adds to a non-conjugated carbon–carbon triple bond under the
action of an ammonium catalyst leading to a cyclic product. Studies in
homogeneous systems suggest that the ammonium agent facilitates cyclitive
nitrogen–carbon bond formation through a cation–π interaction with the alkyne
unit. Using Raman spectroscopy, this cation–π interaction is directly observed for
the first time. DFT modeling elucidated the mechanistic factors in this
cycloaddition.
A teaching experiment was developed based on this mechanistic investigation.
Control experiments were employed to demonstrate the testing of two alternative
mechanistic hypotheses. Cyclization reactions were performed with a soluble base
(sodium phenoxide) with and without tetrabutylammonium bromide under
homogeneous conditions. Students observed that ammonium salt accelerates the
reaction. They were encouraged to develop a testable hypothesis for the role of
the ammonium salt in the cyclization mechanism: typical phase transfer or other.
IR spectroscopy was used to directly observe a dose dependent shift of the alkyne
stretching mode due to a cation−π interaction. Undergraduates were able to
employ the scientific method on a contemporary system and see how data are
generated and interpreted to adjudicate between rival hypotheses in a way that
emulates authentic and current research in a lab setting. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2018. / FAU Electronic Theses and Dissertations Collection
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Studies on Nickel-Catalyzed Reactions via Alkyne Insertion into Carbon-Sulfur Bonds / ニッケル触媒による炭素-硫黄結合へのアルキン挿入を伴う反応に関する研究Inami, Tasuku 23 March 2015 (has links)
京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第18950号 / 工博第3992号 / 新制||工||1615(附属図書館) / 31901 / 京都大学大学院工学研究科材料化学専攻 / (主査)教授 松原 誠二郎, 教授 辻 康之, 教授 中尾 佳亮 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM
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Studies of Alkyne Cycloaddition Reactions Leading to Isoxazolines and Pyrazolines and Synthesis of Urofuranoic Acids to Assess their Effect on Insulin SecretionUnknown Date (has links)
The present thesis will be largely focused on identifying and understanding the scope and mechanistic details associated with the tetrabutylammonium fluoride (TBAF) mediated cyclization of alkynyl hydrazines and (O)-hydroxylamines. Also, the synthesis of 2-(2-carboxyethyl)-4-methyl-5-propylfuran-3-carboxylic acid (CMPF) and its analogs will be discussed along with an analysis of their effects on insulin secretion.
Chapter 1 will present the importance of developing isoxazoline and pyrazoline type heterocycles given that they are continually demonstrated to possess a variety of biological activities. Further, the scope of the reaction in terms of functional group tolerability, scalability and mild conditions will be shown. To expand the importance of this work, a route to access non-racemic heterocycles is also noted. With the heterocycles in hand, new methods were developed to generate more complex frameworks in the form of a novel one pot deprotection/functionalization reaction. Chapter 2 will focus on mechanistic investigations of the cyclization. From the initial discovery of the reaction, its actual mechanism was unknown and a main point of interest. What appeared unusual is that a nucleophilic attack occurs on an unactivated triple bond. Given the identity of the products, a reasonable proposal was a 5-endo-dig type cyclization. However, such a pathway would result in the generation of a vinyl anion intermediate which is well known to be of very high energy and it would seem unlikely to occur under mild conditions. Various trapping experiments were used to demonstrate that the vinyl anion forms and a 5-endo-dig-cyclization is the operative mechanism.
Chapter 3 analyzes the importance of the tetrabutylammonium fluoride reagent. During optimization studies, it became clear that this base is the ideal reagent to facilitate the cyclization although other bases can also enable the transformation at much slower rates. Addition of non-basic ammonium salt additives to bases such as KF and CsF had a dramatic effect on the rate of the reaction. To determine whether the observed rate differences were merely a phase transfer effect or something more, both empirical and Raman spectroscopy data were collected. Based on this, the first evidence for an ammonium-alkyne cation-pi type interaction was shown.
Chapter 4 will summarize the work on the synthesis of 2-(2-carboxyethyl)-4-methyl-5-propylfuran-3-carboxylic acid (CMPF) and its analogs in order to be used in various biological assays. The main goals were to determine a possible structure activity relationship between the substrates and insulin secretion in beta cells and also determine the fate of CMPF in vivo. Several 13C labeled analogs of CMPF were synthesized and successfully used to show for the first time that CMPF in metabolized in vivo in mice. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2017. / FAU Electronic Theses and Dissertations Collection
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Síntese de 1,2,3- triazóis ligados a 1,4- naftoquinona via reação de cicloadição 1,3- dipolar / Synthesis of 1,2,3- triazoles connected 1,4-naphthoquinone via reation of 1,3-dipolar cycloaddition.NASCIMENTO, Wilson Silva do 15 February 2011 (has links)
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Previous issue date: 2011-02-15 / In the present study was performed the synthesis of a new series of 1,2,3- triazole derivative 1,4-disubstituted naphthoquinone group containing the position of a heterocyclic ring from the reaction of 1,3-dipolar cycloaddition between the two precursor azido-1,4-naphthoquinone and 10 terminal alkynes, using a method that employs the use of CuI as the catalytic species for the regioselective formation of the triazole and acetonitrile as solvent. Other methods were also tested, including the one described by using Sharpless reducing environment, however, these methods were less effective or not promoted the formation of the triazole ring. Two of these triazoles had obtained the hydroxyl groups present in its structure acetylated methodology developed in our laboratory using acetic anhydride and montmorillonite K-10 by ultrasound, a total number of 12 new structures of [1,2,3]-triazole 1,4- disubstituted. A second route to obtain 1,4-disubstituted triazoles connected to 1,4- naphthoquinone was proposed from the reaction between 2-ethynyl-1,4- naphthoquinone and azido compound, for it was synthesized the 2-(3-hydroxy-3- metilbutinil)-1,4-naphthoquinone. However, the subsequent reaction of deprotection of this compound, as well as the synthesis of the precursor 2-trimethylsilyl-1,4- naphthoquinone did not work. All the products of unknown structures were characterized by 1H NMR and 13C NMR, elemental analysis, LC-MS and infrared. / No presente trabalho foi realizada a síntese de uma nova série de derivados 1,2,3-triazólicos 1,4-dissubstituídos contendo o grupo naftoquinona na posição 1 deste anel heterocíclico a partir da reação de cicloadição 1,3-dipolar entre o precursor 2-azido-1,4-naftoquinona e 10 alcinos terminais, utilizando um método que emprega o uso de CuI como espécie catalítica para a formação regiosseletiva do anel triazólico e acetonitrila como solvente. Outros métodos também foram testados, entre eles o descrito por Sharpless que utiliza meio redutor, no entanto, estes métodos mostraram-se menos eficiente ou não promoveram a formação do anel triazólico. Dois destes triazóis obtidos tiveram os grupos hidroxilas presente em sua estrutura acetilados por metodologia desenvolvida em nosso laboratório utilizando anidrido acético e montmorillonite K-10 em ultra som, totalizando uma série de 12 novas estruturas de [1,2,3]-triazóis 1,4-dissubstituídos. Uma segunda rota para a obtenção dos derivados triazólicos 1,4-dissubstituídos ligados à 1,4- naftoquinona foi proposta a partir da reação entre o 2-etinil-1,4-naftoquinona e azido composto, para isso, foi sintetizado o 2-(3-hidroxi-3metilbutinil)-1,4-naftoquinona. No entanto, a subseqüente reação de desproteção deste composto, assim como, a síntese do precursor 2-trimetilsilil-1,4-naftoquinona não funcionou. Todos os produtos obtidos de estruturas inéditas foram caracterizados por espectroscopia de RMN 1H e RMN 13C, análise elementar, LC-MS e infravermelho.
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Studies On The Reaction Of Acyl Phosphonates With Aldehydes In The Presence Of ProlineYalcinkaya, Hatice 01 February 2009 (has links) (PDF)
Acyl phosphonates are interesting precursors for the synthesis of biologically active compounds. In the first part, the acyl phosphonates are synthesized starting from the corresponding acyl chloride. The acyl chlorides are converted into acyl phosphonates by using trialkylphosphites.
The reaction of acyl phosphonates with aldehydes in the presence of proline furnished not the suggested aldol products via proline catalyzed aldol reaction but bicyclic products via one pot tricomponent 1,3-dipolar cycloaddition reaction. The formation of the bicyclic compound was suggested as followed / The formation of iminium salt of proline with aldehyde followed by decarboxylation furnished azomethine. The 1,3-dipolar cycloaddition of the formed azomethine with carbonyl group of acyl phosphonate afforded substituted hexahydro pyrrolo oxazole structures.
1,3-Dipolar cycloaddition forms the basis of the most preparatively useful procedures for the synthesis of five-membered heterocycles. One example is the 1,3-dipolar cycloaddition of azomethine ylides (from imines) and alkenes, which allows the stereoselective synthesis of pyrrolidines or proline derivatives.
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Síntese, Elucidação E Avaliação Da Atividade Antimicrobiana De Novas Oximas Isoxazolínicas Aza-BicíclicasSILVA, Lucas Pereira Souza Da 03 August 2014 (has links)
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Previous issue date: 2014-08-03 / Capes / Em estudos prévios, realizados por Almeida, foram obtidas substâncias 2-isoxazolinas
aza-biciclicas, que deram origem a núcleos como o 2-isoxazolina[5,4-b]piperidina e 2-
isoxazolina[5,4-b]pirrolidina. Amidas N benzoiladas derivadas dessas substâncias
apresentaram-se farmacologicamente ativas, principalmente em testes anti-inflamatório e
antimicrobianos realizados com esses compostos. Além disso, várias substâncias
contendo a função oxima, em sua forma livre e como éteres de oxima, são descritas na
literatura, apresentando atividades biológicas antimicrobianas. Diante disso, foi obtido
através da hibridização molecular, derivados 2-isoxazolínicos aza-biciclico contendo a
função oxima em sua estrutura. Os ésteres isoxazolínicos 34 e 36 foram obtidos através
de reações de cicloadição 1,3-dipolar por duas diferentes rotas sintéticas, pela reação do
óxido de nitrila 41 (CEFNO) tanto com o enecarbamato cbz, quanto com as enamidas
endocíclicas para-substituídas. Os cicloadutos oriundos do enecarbamato endocíclico,
sofreram reações de hidrogenólise e posterior N-benzoilação. A porção éster, presente
nos compostos N-benzoilados para-substituídos, foi reduzida a álcool e em seguida
submetida a uma oxidação de Swern, resultando nos aldeídos isoxazolínicos. A partir
desses aldeídos 38, através de uma reação com hidroxilamina, chegou-se nas oximas
isoxazolínicas 39. Os novos derivados foram submetidos a testes biológicos com o intuito
de avaliar sua atividade antimicrobiana. O teste foi realizado pelo método de difusão em
disco, contendo bactérias Gram negativas e Gram positivas, onde os derivados
isoxzolínicos apresentaram halos variados frente aos microrganismos em estudo. O
composto 39b caracterizou-se como uma substância promissora no desenvolvimento de
novos agentes antimicrobianos, com halos de 10 mm para o Staphylococcus aureus, 11
mm para o Micrococcus luteus, 13 mm Bacillus subtilis e 13 mm para o microrganismo
Micobacterium smegmatis. / In previous studies conducted by Almeida substances were obtained isoxazolines 2-azabicyclic,
giving rise to nuclei as 2-isoxazoline [5,4-b] piperidine and 2-isoxazoline [5,4-b]
pyrrolidine. N benzoiladas amides derived from these substances had become
pharmacologically active, especially in anti-inflammatory and antimicrobial tests conducted
with these compounds. Furthermore, substances containing various oxime function, in free
form and as oxime ethers are described in literature, showing microbial biological activities.
Thus, was obtained by molecular hybridization, derivatives aza-bicyclic 2-isoxazolínicos
containing the oxime function in its structure. Esters isoxazolínicos 34 and 36 were
obtained by cycloaddition 1,3-dipolar cycloaddition reactions of two different synthetic
routes, by reaction of the nitrile oxide 41 (CEFNO) with both the cbz enecarbamate, as
with the endocyclic enamides para-substituted. Cicloadutos coming from the endocyclic
enecarbamate suffered reactions of hydrogenolysis and subsequent N-benzoylation. The
ester moiety present in the N-substituted compounds for benzoilados was reduced to
alcohol, and then subjected to a Swern oxidation, resulting in isoxazolínicos aldehydes.
From these aldehydes 38 by means of a reaction with hydroxylamine, was reached in
isoxazolínicas oximes 39. The novel derivatives were subjected to biological tests in order
to evaluate its antimicrobial activity. The test was performed using the disk diffusion
method, comprising Gram negative and Gram positive where isoxzolínicos halo derivatives
showed varied across the microorganisms under study. Compound 39b was characterized
as a promising substance in the development of new antimicrobial agents with halos of 10
mm for Staphylococcus aureus, 11 to Micrococcus luteus mm, 13 mm and 13 mm Bacillus
subtilis microorganism Mycobacterium smegmatis for.
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Synthesis and Evaluation of 1,2,4-oxadiazolidinones: The Search for A Potential Non-β-lactam β-lactamase Inhibitors.Kalu, Chimdi Eke 01 May 2019 (has links) (PDF)
β-lactam antibiotics have been the most widely used drug of choice to combat infectious disease caused by bacteria. Unfortunately, their effectiveness is drastically threatened by bacterial β-lactamases. β-lactamases is responsible for the resistance to most antibiotic drugs. For decades, β-lactam β-lactamases inhibitors have been used to reduce bacterial resistance; however, in this study 1,2,4-oxadiazolidinone derivatives as a non-β-lactam β-lactamases inhibitor against TEM-1 and P99 β-lactamases. The significance of oxadiazolidinone is the prominent five-membered ring scaffold in its structure, which is configurationally stable and present in other biologically active compounds such as linezolid and avibactam. Oxadiazolidinones were synthesized by treating nitrones with isocyanates. The synthesized compounds were characterized using 1H and 13C NMR, GC-MS, and FTIR. Afterward, they were tested using Nitrocefin as substrate to determine their effectiveness against TEM-1 and P99 serine β-lactamase. Compound 2a-2c, and 3 showed inhibition ranging from 12-38%.
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3-azetidinonas e 3-azetidinois : preparação e aplicações na sintese de azetidinas substituidas / Azetidin-3-ones and Azetidin-3-ols: preparation and applications in the synthesis of substituted AzetidinesBurtoloso, Antonio Carlos Bender 03 March 2006 (has links)
Orientador: Carlos Roque Duarte Correia / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Quimica / Made available in DSpace on 2018-08-05T22:30:16Z (GMT). No. of bitstreams: 1
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Previous issue date: 2006 / Doutorado / Quimica Organica / Doutor em Ciências
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