Dissertations / Theses on the topic 'Lactams'
To see the other types of publications on this topic, follow the link: Lactams.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'Lactams.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Betou, Marie. "Semipinacol rearrangement of cis-fused β-lactam diols into bicyclic lactams." Thesis, University of Birmingham, 2013. http://etheses.bham.ac.uk//id/eprint/4348/.
Abstract:
The 6-azabicyclo[3.2.1]octane ring system is found in a wide variety of biologically active natural and non-natural products. The aim of this project is to prepare the 7,8-diketo-6-azabicyclo[3.2.1]octane structure via a semipinacol rearrangement of ring-fused β -lactams. Chapter 1 introduces the pinacol and semipinacol rearrangement, including the use of cyclic sulfites and phosphoranes, and ring expansion of β -lactams. Previous work in the Grainger group for the synthesis of lactams via tandem radical cyclisation-dithiocarbamate group transfer is also discussed. Chapter 2 describes the methodology developed for the semipinacol rearrangement of β-lactams. Access to suitable precursors for the semipinacol rearrangement is achieved through a sequence of 4-exo trig radical cyclisation, base-mediated dithiocarbamate group elimination and dihydroxylation. Formation of the 7,8-diketo-6-azabicyclo[3.2.1]octane ring system occurs through semipinacol rearrangement of the corresponding cyclic sulfites and phosphoranes. In Chapter 3, the scope and limitations of the methodology are explored. Different substituents on the nitrogen of the β-lactam, groups on the cyclohexane moiety (methyl and oxygenation) and ring sizes are investigated. An original approach to the total synthesis of peduncularine is described in Chapter 4. Synthesis of a suitably functionalised β-lactam and attempts to further transform it into the desired 7,8-diketo-6- azabicyclo[3.2.1]oct-3-ene structure are reported. Work towards the total synthesis of calyciphylline D, calyciphylline F and caldaphnidine M is described in chapter 5. Reductive amination and stereoselective reduction of piperitone are investigated. Use of a model system for the addition of nucleophiles onto thiolactams is also described.
2
Warren, H. A. "New routes to sugar lactams, lactim ethers and cyclic amidines." Thesis, Swansea University, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.639351.
Abstract:
Chapter 1 introduces the biological importance of glycosidase inhibitors. The biosynthesis of N-linked glycoproteins is briefly described and the mode of action of glycosidase enzymes is discussed. Some naturally occurring amino-sugar glycosidase inhibitors are detailed. In addition certain sugar lactones, lactams and cyclic amidines which have also been shown to inhibit glycosidase enzymes are reviewed. Chapter 2 introduces the syntheses of various polyhydroxylated piperidine and pyrrolidine alkaloids and sugar lactams. In addition the formation of cyclic sugar amidines and their derivatives is discussed. Chapter 3 involves the syntheses of four novel sugar lactams. The syntheses of 4-amino-4-deoxy-D-allonolactam and 4-amino-4-deoxy-D-talonolactam via novel routes developed by the author are dealt with in detail. The preparations of the corresponding D- and L-ribono compounds by a shortening of the carbon chain are also described. Chapter 4 introduces the syntheses of the novel D-allono-, D-talono- and D-ribono- amidines from the corresponding lactam derivatives. Chapter 4 also reports on literature preparations of sugar tetrazoles and their inhibitory properties towards glycosidase enzymes. Also included is the synthesis of the novel D-talonotetrazole.
3
Guignard, Guillaume Michel Pablo. "Open-chain building blocks from chiral lactams. Enantioselective synthesis of macrocyclic nitrogen-containing natural products." Doctoral thesis, Universitat de Barcelona, 2016. http://hdl.handle.net/10803/396650.
Abstract:
1. (R)-Phenylglycinol-derived oxazolopiperidone lactams can be converted to enantiopure open-chain amino ester scaffolds by alkaline hydrolysis of the N-Boc 2-piperidones resulting from the reductive cleavage of the oxazolidine ring.
2. Lithium amidotrihydroborate (LiNH2BH3) reduction of diversely substituted (R)-phenylglycinol-derived oxazolopiperidone lactams brought about the reductive opening of both the oxazolidine and lactam rings, providing general access to structurally diverse enantiopure amino diols A bearing a variety of substitution patterns, substituents (alkyl, benzyl, aryl, protected hydroxy), and stereochemistries.
3. Reductive removal of the phenylethanol moiety present in the amino diols prepared by the above procedure, followed by treatment of the resulting primary amines with (Boc)2O provides a general synthetic entry to enantiopure N-Boc 5-aminopentanols bearing substitutents at the 2-, 3-, 4-, 2,2-, 2,3-, 2,4-, and 3,4- positions.
4. The oxidative removal of the phenylglycinol moiety of amino diols A (previously O-silylated) using the I2/aq NH3 system constitutes an excellent procedure for the straightforward preparation of enantiopure substituted 5-hydroxypentanenitrile derivatives.
5. The m-CPBA-promoted oxidative removal of the phenylglycinol moiety of amino diols A (previously O-silylated) constitutes an excellent procedure for the straightforward preparation of enantiopure substituted 5-hydroxypentanoic acid derivatives.
6. As both enantiomers of phenylglycinol are commercially available, both enantiomers of a target 5-aminopentanol, 5-hydroxypentanoic acid, and 5-hydroxypentanenitrile are accessible through the above methodology.
7. The synthetic value of the open-chain amino diols A has been demonstrated with their use as key scaffolds for the enantioselective synthesis of the Haliclona alkaloids haliclorensin C (first total synthesis), haliclorensin (total), halitulin (formal), and isohaliclorensin (formal).
8. The synthetic value of the open-chain amino diols 5-hydroxypentanoic acids, and 5-hydroxypentanenitriles prepared from (S)-phenylglycinol-derived lactams has been demonstrated with their use as key scaffolds for the synthesis of the natural macrolactam fluvirucinin B1.
9. The approach we have developed significantly expands the potential of phenylglycinol-derived d-lactams, which have been converted for the first time to enantiopure open-chain building blocks.
4
Sheppard, L. N. "Synthesis of B-lactams." Thesis, University of Oxford, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.354855.
5
McKenna, Jeffrey M. "Asymmetric synthesis of #beta#-lactams." Thesis, University of Oxford, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.240681.
6
Goh, Kee Chuan. "The biosynthesis of β-lactams." Thesis, University of Oxford, 1993. http://ora.ox.ac.uk/objects/uuid:24b6b29d-87cc-48f2-bd1b-bb64c663604f.
Abstract:
This thesis reports the work done on two research projects which were carried out independently of each other but converge on the central theme of β-lactam biosynthesis. Chapter 1 provides an overview of biosynthesis in secondary metabolism, with special emphasis on current knowledge about the β-lactams. The first project, covered from Chapters 2 to 5, was part of our group's continuing effort to understand the structure and mechanism of Ring Expandase-Hydroxylase (REXH), an enzyme involved in the biosynthesis of cephalosporin C in Cephalosporium acremonium. REXH is a bifunctional enzyme, converting penicillin N to DAOC and thence to DAC. [diagram omitted from transcription] Chapter 3 discusses the investigation of purification protocols for native REXH and soluble recombinant REXH, as well as an improved refolding method for recombinant REXH expressed as inclusion bodies. Chapter 4 describes two new alternative substrates for REXH, viz. carba-DAOC and DAC, whilst the y-lactam analogue of penicillin N was not found to be a substrate for REXH. Chapter 5 summarises some structural investigations of REXH employing methods such as electrospray mass spectrometry, selective proteolysis and inhibition kinetics. [diagram omitted from transcription] The second project, covered from Chapters 6 to 9, represents the first biosynthetic studies on valclavam, an antifungal produced by Streptomyces antibioticus. Valclavam belongs to the family of clavams which includes clavulanic acid as its most well studied member. [diagram omitted from transcription] Chapter 7 details the development of methods for the bioassay, fermentation and isolation of valclavam. It also describes the isolation of a stable degradation fragment of valclavam which led to the revision of the structures of valclavam and Tü 1718B (another metabolite from the same organism). Chapter 8 gives an account of the whole-cell feeding experiments which strongly suggest that the primary metabolic precursors for valclavam are L-valine, L-arginine, L-methionine and glycerol. Chapter 9 reports the discovery of two enzymic activities, belonging to those of clavaminic acid synthase and proclavaminic acid amidino hydrolase, which are likely to be involved in the biosynthesis of valclavam. Together, the results of Chapters 8 and 9 point to an extensive overlap between the clavulanic acid pathway in Streptomyces clavuligerus and the valclavam pathway in Streptomyces antibioticus.
7
Welchman, Elizabeth Victoria. "The chemistry of β lactams." Thesis, University of Sunderland, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.247775.
8
Walker, Matthew David. "Diastereoselective reactions of atropisomeric lactams." Thesis, University of Nottingham, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.247569.
9
Pearson, C. J. "Synthesis of aza-beta-lactams." Thesis, Imperial College London, 1985. http://hdl.handle.net/10044/1/37815.
10
Pérez, Bosch Maria. "Addicions conjugades a lactames bicícliques derivades del fenilglicinol: síntesi enantioselectiva de piperidines 3,4- i 3,4,5-substituïdes." Doctoral thesis, Universitat de Barcelona, 2002. http://hdl.handle.net/10803/673099.
Abstract:
La adición conjugada de cianocupratos de orden inferior a las lactamas insaturadas derivadas del fenilglilcinol transcurre con buenos rendimientos y elevada selectividad facial. En aquellas que poseen un sustituyente etilo en posición contigua al carbono electrófilo del doble enlace proporciona estereoselectivamente productos con una relación cis entre el sustituyente carbonado introducido y el grupo etilo. Estos resultados pueden justificarse considerando que la conformación del anillo de piperidina se halla condicionada por la configuración de un estereocentro, independientemente de la presencia de un sustituyente etilo, y que el ataque del cianocuprato tiene lugar bajo control estereoeléctrónico proporcionando el producto de control cinético debido a la irreversibilidad de la reacción.
Por otro lado, la adición de aniones estabilizados a una lactama insaturada que posee un sustituyente etilo contiguo al carbono electrófilo del doble proporciona compuestos que guardan una relación trans entre el sustituyente carbonado introducido en la adición y el grupo etilo. La estereoselectividad observada es atribuible a la reversibilidad de la reacción de adición conjugada de aniones estabilizados, lo que conduce al compuesto termodinámicamente más estable.
La utilidad sintética de las anteriores reacciones de adición conjugada se ha puesto de manifiesto con la síntesis enantioselectiva de diversas piperidinas cis- y trans-3,4-disustituidas.
11
Wallace, P. M. "Approaches to synthesis of beta-lactams." Thesis, University of Oxford, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.355808.
12
Jones, Mark. "The enzyme catalysed formation of lactams." Thesis, University of Huddersfield, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.293346.
13
Nadin, Alan. "Medium ring lactams as peptidic constraints." Thesis, University of Cambridge, 1993. https://www.repository.cam.ac.uk/handle/1810/272640.
14
Shah, Ajit Jesang. "The analysis of #beta#-lactams and their biosynthetic intermediates in fermentations of #beta#-lactam producing fungi." Thesis, University of Westminster, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.358855.
15
Derrer, Sam. "Medium ring lactams as peptide conformational constraints." Thesis, University of Cambridge, 1998. https://www.repository.cam.ac.uk/handle/1810/251637.
16
Virden, Jane. "Chemical and enzymatic synthesis of #beta#-lactams." Thesis, University of Oxford, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.253475.
17
Dixon, Rachel Anne. "Asymmetric reduction of meso-imides and lactams." Thesis, University of Newcastle Upon Tyne, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.399101.
18
Khaled, Arwa M. "Heterometallic complexes with lactams and related ligands." Thesis, Imperial College London, 1991. http://hdl.handle.net/10044/1/46864.
19
Kenwright, Jayne Louise. "Synthesis of medium ring amines and lactams." Thesis, University of Cambridge, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608700.
20
Philippe, Jules. "Pneumococcus morphogenesis and resistance to beta-lactams." Thesis, Grenoble, 2014. http://www.theses.fr/2014GRENV018/document.
Abstract:
Streptococcus pneumoniae, le pneumocoque, est une bactérie pathogène qui entraîne le décès de plus d'un million et demi de personnes dans le monde chaque année. Les β-lactamines sont très utilisées pour traiter les infections à pneumocoques. Ces antibiotiques inhibent la synthèse du peptidoglycane, une molécule géante constituant un réseau de chaînes glycopeptidiques qui englobe la cellule, lui confère sa forme et lui permet de maintenir son intégrité face à la pression osmotique. Le mécanisme d'action des β-lactamines est bien connud'un point de vue biochimique. En revanche, la réponse physiologique empêchant la multiplication des bactéries traitées est mal connue. Au cours de ma thèse, j'ai étudié les mécanismes moléculaires de la morphogenèse du pneumocoque par des approches de biochimie et de microbiologie. Un modèle de morphogenèse est proposé intégrant mes résultats à la littérature et permettant de formuler des hypothèses sur la réponse physiologique de S. pneumoniae aux β-lactaminesStreptococcus pneumoniae, the pneumococcus, is a bacterial pathogen that causes more than 1.5 million deaths each year in the world. β-Lactams are widely used to treat patients with pneumococcal infections. These antibiotics inhibit the synthesis of the peptidoglycan, a giant molecule constituting a mesh of aminosugar strands encasing the cell. This main constituent of the cell wall allows cells to maintain their integrity under the turgor pressure, and endows bacteria with their shape. The action of β-lactams is well understood from a biochemical point of view. However, a complete understanding of the physiological response of treated bacteria remains elusive. In this thesis, I investigated the molecular mechanisms of the morphogenesis of S. pneumoniae using methods of biochemistry and microbiology. A morphogenesis model is built based on my results and the literature, which permits to emit hypotheses concerning the response of the pneumococcus to β-lactams
21
Micheli, Bernard Jean Marie. "NMR studies of dimeric and polymeric lactams." Diss., The University of Arizona, 1990. http://hdl.handle.net/10150/185270.
Abstract:
The aim of this work was to study the solution conformation of dimeric and polymeric 1actams. In a first part of this work, the synthesis of bicyc1odi1actams as precursors of the polymers was explored. A new preparation for the 2, 5-diazabicyc1o [2,2,2] octa-3, 6-dione was developed. The dimers and polymers were obtained from the N-protected cis- and trans- 3-amino-6-carboxy-2-piperidone for which an improved synthesis was found. Base treatment of the trans activated ester led to the polymer. Using the methods of solution phase peptide synthesis, the four possible dimers were prepared. After transformation to the paranitrophenyl esters, they polymerized to oligomeric species under the same treatment. The solution conformation of the monomeric, dimeric and polymeric species was determined by 1- and 2-dimensional NMR techniques. The 1actam rings have a chair-like conformation in solution. The cis- 1actam is a powerful β-turn- inducer when incorporated in synthetic peptides. The cis- lactam was found, however, to have a very similar conformation in DMSO solution, without hydrogen bonding to stabilize the turn. No evidence was found for the β-turn in the dimers and polymers using 2-dimensional NMR techniques. The dimers were found to exist in an extended conformation in DMSO. The fact that every other amide bond is in the cis configuration, as well as the steric crowding due to the rings may not allow the existence of the β-turn.
22
Westwood, Nicholas James. "Synthetic and mechanistic studies on the inhibition of elastases." Thesis, University of Oxford, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.306872.
23
Shakya, Sagar Raj. "Studies on alpha,alpha-disubstituted bicyclic beta-lactams." Thesis, University of Ottawa (Canada), 1992. http://hdl.handle.net/10393/7571.
Abstract:
General Organization. This thesis contains a brief introduction to the area of $\beta$-lactam antibiotics and four other Chapters dealing with the syntheses of various 6-methoxy $\beta$-lactams. Due to the tremendous level of activity in this area the introductory literature material is presented in an illustrative approach rather than a comprehensive approach. Literature surveys were carried out using Chemical Abstracts from 1982 to February 1992. Experimental details are given at the end of each Chapter. Compounds in the schemes which did not lead to desired conclusion were not completely characterized; $\sp1$H NMR and other spectral data whenever available are given in the Experimental section. IR was not recorded in most of these cases. Elemental analyses were not performed at all, since the data from such experiments do not always represent the purity of product. Chapter 1. This section describes the development of various $\beta$-lactam antibiotics, major representative structures, mode of action and overall objectives of the research undertaken. Chapter 2. 7-Methoxy-7-ethyl and 7-methoxy-7-hydroxyethylisocephem analogs were prepared from 4-cinnamyl-3-methoxyazetidinone which was prepared in a multigram scale. This precursor can be purified simply by trituration with ether. The transformation of this monocyclic starting material to the cyclization precursor involved introduction of an additional side-chain at C-3 via. generation of anion using lithium diisopropylamide and quenching of the anion with either ethyl iodide or acetaldehyde. In the case of the hydroxyethyl side-chain oxidation with pyridinium chlorochromate, reduction with L-Selectride and silylation with tert-butyldimethylsilyl triflate was required before carrying out further manipulations. The cinnamyl group was converted to a methylene bearing a leaving group and the p-methoxyphenyl moiety on nitrogen was cleaved and a suitable acetate side-chain was introduced. The anionic annulation with CS$\sb2$ gave the desired bicyclic compounds. An optically active isocephem having a thienamycin type side-chain at C-7 and and a racemic isocephem having a methoxy group at C-7 were prepared by similar method. Chapter 3. 7-Ethyl-7-methoxycarbacephem was prepared using a rhodium carbenoid reaction starting from 4-cinnamyl-3-methoxyazetidinone. A similar method was applied to prepare an advanced intermediate for 7-hydroxyethyl-7-methoxycarbacephem. Chapter 4. 6-Methoxy-PS 5 synthesis was attempted which was found to be unstable. The cyclization was carried out applying the rhodium carbenoid methodology. The cyclization precursor was obtained using nitroaldol condensation starting from an aldehyde which was prepared from 4-cinnamyl-3-methoxyazetidinone. Chapter 5. Syntheses of 6-methoxy-1-methyl-PS 5 analogs were attempted starting from 3-ethyl-3-methoxy-4-methylcinnamylazetidinone. The introduction of 1-methyl group involved the reduction of a suitable $\alpha,\beta$-unsaturated ester obtained via. palladium catalyzed carbonylation reaction.
24
Kang, T. W. "Novel synthesis of #beta#-lactams via radical pathways." Thesis, University of Oxford, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.379970.
25
Goswami, Rajesh. "Bicyclic lactams for the synthesis of functionalised heterocycles." Thesis, University of Oxford, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.365826.
26
Gardiner, James. "Conformationally restricted amino acid analogues based on lactams." Thesis, University of Canterbury. Chemistry, 1998. http://hdl.handle.net/10092/8773.
Abstract:
This thesis describes the synthesis of enamino esters 3(S)-(E)-benzoylamino-3-benzyl-
5-ethoxycarbonylmethylidene-1-methylpyrrolidin-2-one 77, and 3(S)-(E)-benzoylamino-3-benzy 1-5-ethoxycarbonylmethylidene-1-2, 4-dimethoxybenzy lamino-pyrrolidin-2-one 79. These were designed as a new class of conformationally restricted amino acid analogue.
Chapter one gives a general introduction to the importance of peptides in nature and the pivotal role peptides play in drug discovery and design. A number of examples are examined to provide an insight into key elements required in peptidomimetic design.
Chapter two introduces the process of peptidomimetic design, in particular that of cisamide bond mimics. The synthesis of a new class of conformationally restricted peptidomimetic based on lactams is examined.
Chapter 3 discusses the synthesis of succinic acid-derived, and aspartic acid-derived,
β-keto esters and amides 23, 24, 28, via a Meldrum's acid procedure. This method provides the basis for the preparation of cyclic enamino esters. The preparation of the β-keto amide methyl-5-(N-ethoxycarbonylmethylcarbamoyl)-4-oxo-pentanoate 24 allowed chain extension in the C-direction in one easy step.
Chapter 4 examines the importance of ene-lactams in nature and the synthesis of enamino esters 55, 56, 59, 61, and enamino amides 63 and 64,.via the reaction of a β-keto ester, or amide, with an amine. Compounds 59 and 61 represent examples of 3- substituted cis-amide bond mimics that allow chain extension in both the N and C directions and subsequent incorporation into a peptide sequence.
Chapter 5 describes the synthesis of the target phenylalanine-derived 3,3-disubstituted enamino esters 77 and 79, using the methodology established in chapter 4. Reaction of the enolate derived from (2R, 4S)-2-phenyl-3-benzoyl-4-benzyl-1,3-oxazolidin-5-one 65, with tert-butylbromoacetate gave (2R, 4S)-2-phenyl-3-benzoyl-4-benzyl-4-(tertbutyloxycarbonylmethyl)-1,3-oxazolidin-5-one 67. An x-ray crystal structure of 67 revealed that the reaction had proceeded with an inversion of configuration at C4, with the oxazolidinone ring being essentially planar in the solid state. This also revealed that the stereochemistry at C3 could be determined by the stereochemistry of the amino acid from which it was derived. The tert-butyl ester was hydrolyzed and the resulting acid was converted to the β-keto ester 71 upon reaction with meldrum's acid and EtOH. The
β-keto ester (2R, 4S)-2-pheny 1-3 -benzoy 1-4-benzy 1-4-(3 -ethoxycarbony 1-2-oxopropyl)-1 ,3-oxazolidin-5-one 71, was reacted with either methylamine, or 2,4-
dimethoxybenzylamine (DMBNH₂), and heated at 150°C, under reduced pressure, to give the target 3,3-disubstituted enamino esters 77 and 79. The target enamino ester 77 and 79 allow chain extension in both the N and C-directions and are designed to be incorporated into a peptide sequence to mimic a cis-amide bond and allow investigation into the bio-active conformation of a specific peptide.
27
Pink, Jennifer Helen. "Synthesis of fused lactams via N-acyliminium ions." Thesis, University of Sheffield, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.242373.
28
Ajavakom, Anawat. "Novel radical based routes to pyrrolidine trans lactams." Thesis, University of Southampton, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.288468.
29
Fontana, Francesco. "Stereoselective synthesis of β-lactams and carpanone derivatives." Paris 6, 2008. http://www.theses.fr/2008PA066441.
Abstract:
SECTION A Nous décrivons la synthèse de nouveaux dérivés 4-spiro--lactamiques, au moyen de réactions de Staudinger entre des cétènes dérivant des -aminoacides cycliques énantiopurs (dérivés protégés de l’acide 1,3-thiazolidine-2-carboxylique et de la 4-hydroxy-L-proline) et des imines riches en électrons. Nous avons ensuite évalué la réactivité des composés obtenus conduisant à des produits -lactamiques mono- ou polycycliques totalement nouveaux et intéressants. SECTION B La carpanone est un lignane possédant cinq centres stéréogènes contigus qui a été isolée sous forme racémique de l'arbre carpano. A l’heure actuelle, il n’existe qu’une seule stratégie de synthèse de cette molécule limitée quant à la diversité moléculaire. Nous avons mis au point une nouvelle synthèse plus flexible que la seule méthode décrite jusque là et permettant d’obtenir facilement une librairie d’analogues. Nous avons obtenu alors la carpanone en six étapes à partir du sésamol, avec un rendement global de 55%.
30
Naz, Summia. "A calorimetric study of β-sultams and β-lactams." Thesis, University of Huddersfield, 2009. http://eprints.hud.ac.uk/id/eprint/6975/.
Abstract:
The hydrolytic degradation of a series of β-sultams and β-lactams was investigated using isothermal microcalorimetry (IMC), to determine kinetic and enthalpic data. The importance of these studies was to model the process of hydrolysis as this was a simplification of the mechanism by which β-lactams and β-sultams function as serine protease inhibitors. Calorimetric studies were conducted using a Thermal Activity Monitor (TAM 2277). Three categories of experiments were conducted: in the solid state, varying relative humidity (R/H) and in aqueous solution. Hydrolytic rate constants and enthalpies were determined for the solid state studies and these were related to substituent effects. However, for the experiments relating to the R/H studies no conclusive results were obtained. As expected, for solution state studies the hydrolytic rate constant in all cases changed with temperature (298K, 310K and 323K). Theoretical predictions were then made for a novel β-sultam based on these results with an excellent correlation observed between theoretical calculations and experimental results. Finally, calorimetric experiments were conducted on a series of β-lactams. This was for two reasons firstly; to determine if calorimetry can monitor low reaction rates and secondly; to compare rates of hydrolysis with the β-sultams. For a series of β-lactams, solution state hydrolytic rate constants and enthalpies were determined. An overall comparison of β-lactams and β-sultams appeared to indicate that in all cases β-lactams reacted slower than β-sultams.
31
Baugh, Simon Peter. "Alkene metathesis in the synthesis of novel #beta#-lactams." Thesis, Imperial College London, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.300539.
32
Bahajaj, Abood Ahmed. "Asymmetric synthesis of spiro lactams via n-acyliminium ions." Thesis, University of York, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241062.
33
Brown, Giles A. "The azomethine ylide approach to novel bicyclic #beta#-lactams." Thesis, University of Bristol, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.302062.
34
Jackson, Lynn. "Inhibition of elastase and trypsin by novel β-lactams." Thesis, University of Edinburgh, 2002. http://hdl.handle.net/1842/15094.
Abstract:
Elastase is a serine protease that has been implicated in a number of inflammatory conditions including rheumatoid arthritis and cystic fibrosis. These conditions are thought to result from an increased amount of active elastase in the body, caused by insufficient inhibition by endogenous inhibitors. Elastase has the ability to degrade many tissue components and this excessive tissue damage causes the onset of a variety of conditions. This knowledge has led to an increased interest in the production of elastase inhibitors with the hope of developing an inhibitor, which can be of therapeutic use in vivo. As a result we have synthesised a series of novel β-lactams since β-lactam compounds are known to be mechanism-based inhibitors of serine proteases. Electrospray ionisation mass spectrometry (ESI-MS) identified a novel mode of inhibition, for β-lactams which possess a hydroxyl group present at the C3 position, resulting in the formation of an acyl-enzyme intermediate which was found to be extremely stable. Enzyme kinetic studies demonstrated that the β-lactams had kass values ranging from 1000 - 10,000 M-1 s-1. The novel β-lactams were also assayed for activity against trypsin. ESI-MS confirmed that they were also inhibitors or trypsin but enzyme kinetic studies revealed that they were more active towards elastase. Therefore the novel β-lactams were found to be stable, potent and specific inhibitors of elastase that may of therapeutic use in the treatment of many inflammatory conditions.
35
Ghirardi, Elena. "Enantio- and Diastereoselective Cyclocondensation Reactions. Stereocontrolled Access to Azabicycles and Application to Natural Product Synthesis." Doctoral thesis, Universitat de Barcelona, 2016. http://hdl.handle.net/10803/398789.
Abstract:
The first objective of this Thesis was the study of the preparation of octhydro-1H-cyclopenta[b]pyridines and octahydro-1H-indoles, through the synthesis of (R)-phenylglycinol derived tricyclic lactams. Following the previous reported methodology a carbon substituent would be present at the carbocyclic ring and we planned to find the conditions for controlling its absolute configuration. Unfortunately, the reaction of ketoester 4 and ketoacid 7, provided undesired enamines 8 and 9. On the other hand, the reaction of ketoacid derivatives 16 and 17 with (R)-phenylglycinol led to a mixture of epimeric amides 18.
With the aim to extend the methodology, we planned to study the cyclocondensation reaction of (R)-phenylglycinol and (1S, 2R)-aminoindanol with C-3 and C-5 substituted cyclohexanepropionate derivatives. These reactions provided enantiopure tricyclic or pentacyclic lactams: in every run, a major lactam was isolated or identified, and a minor one was detected. The use of (1S, 2R)-aminoindanol resulted in better results. These tricyclic and pentacyclic lactams are precursors of C-8 (and C-6,8) substituted cis-decahydroquinolines. The conversion required the stereoselective reductive cleavage of C-O oxazolidine bond with simultaneous reduction of lactam carbonyl group, and debenzylation. A library of enantiopure cis-decahydroquinolines was obtained. To illustrate the usefulness of our method, we decided to undertake the synthesis of some alkaloids of Myrioneuron nutans family, which contain an 8-substituted cis-decahydroquinoline core. In particular, we prepared the enantiopure alcohol 82, which was described to be a common intermediate in the synthesis of various Mirioneuron nutans alkaloids. Our synthetic procedure greatly improved the previous results reported for the synthesis of this alcohol.
The cyclocondensation reaction of (R)-phenylglycinol and (1S,2R)-aminoindanol with 3-alkyl-2-oxo-cyclohexane-1-acetate derivatives was finally considered. Reaction of (R)-phenylglycinol and 3-alkyl-2-oxocyclohexaneacetate derivatives 97-100 and 107 provided with high yield and stereoselectivity tricyclic lactams 110, 112a, 114, 116 and 118, which incorporate an alkyl or aryl substituent at C-10, while (1S,2R)-aminoindanol did not furnish so good outcomes. These reactions stereoselectively provided an additional minor hexahydroindole by-product. The absolute configuration of these compounds 111a, 113a, 115a and 117a was confirmed by X-ray crystallography. In the case of any or aryl substituent at C-10 of the tricyclic lactam, no by products were detected. We demonstrated that these unsaturated products derived from the opening of the oxazolidine ring of the minor lactams, which are epimers at C-10 of the major lactams, in the presence of acids. The stereoselective opening of the oxazolidine ring of the major lactams, in the presence of strong acids provided unsaturated compounds 111b, 113b, 115b and 117b, in which H-7 and H-7a resulted in cis relative disposition. In the case of lactam 118, with an aryl substituent at C-10, provided the unsaturated compound 125, in which H-7 and H-7a are in relative trans disposition. This different relative configuration can be accounted for by considering the structure rigidity of this system.
Major tricyclic lactams were converted into C-7 exo substituted cis-octahydroindoles and cis-octahydroindolones, by selection of the appropriate reductive conditions. Hexahydroindolones 111b, 113b, 115b and 117b were converted stereoselectively into the corresponding enantiopure C-7 endo substituted cis-octahydroindolones, by catalytic hydrogenation of the carbon-carbon double bond, followed by elimination of the chiral inductor through reaction with sodium radical. Moreover, these hexahydroindolones and 125 were transformed into the corresponding trans-octahydroindolones 146c-149c and 126b by simultaneous reduction and debenzylation in sodium ammonia. The presence of the amide function allowed the stereoselective insertion of a new substituent by a-alkylation and a-amidoalkylation.
Finally, in order to demonstrate the utility of this methodology, (+)-a-Lycorane was synthesized in only four steps, starting from easily available ketone 171, in 35% of overall yield, which resulted an improvement with respect to previously reported synthesis.El primer objetivo de esta Tesis Doctoral ha sido el estudio de la preparación de octahidro-1H-ciclopentapiridinas y octahidro-1H-indoles, a través de la síntesis de lactamas tricíclicas derivadas del (R)-fenilglicinol. Desafortunadamente, la reacción del ceto-éster 4 y del ceto-ácido 7, proporcionó solamente las eniminas 8 y 9. Por otro lado, la reacción de los derivados de ceto-ácidos 16 y 17 con (R)-fenilglicinol rindió únicamente una mezcla de productos 18, amidas conjugadas epímeras en la posición C-7a. Se ha sido estudiado la reacción de ciclocondensación de derivados de 2-oxociclohexano propionato convenientemente sustituidos en C-3 o en C-3 y C-5 con (R)-fenilglicinol y (1S,2R)-aminoindanol. Esta reacción conduce estereoselectivamente a lactamas tricíclicas o pentacíclicas quirales: se aisló mayoritariamente una lactama y se detectó la presencia de otra minoritaria. Al utilizar (1S,2R)-aminoindanol se obtuvieron mejores resultados. Estas lactamas son precursoras de cis-decahidroquinolinas, con sustituyentes en la posición 8 o en la posición 6 y 8. Las etapas clave de esta transformación son la reducción con alano y la eliminación del inductor quiral. Con esta metodología se ha preparado la decahidroquinolina 82, precursor de numerosos alcaloides de la familia Mirioneuron nutans. Además, presentamos el estudio de las reacciones de ciclocondensación con (R)-fenilglicinol a partir de ciclohexanonas que poseen una cadena de acetato en la posición C-1 y diversos sustituyentes alquilo o arilo en la posición C-3. Esta reacción conduce estereoselectivamente a una sola lactama tricíclica de las ocho posibles. A partir de las cetonas con un sustituyente alquilo en la posición C-3 aislamos una cantidad variable de enamida. Las lactamas mayoritarias, fueron convertidas en cis-octahidroindoles y cis-octahidroindolonas, que presentan un sustituyente en la posición 7 o en las posiciones 7 y 7a del anillo carbocíclico. Además, estudiamos la reactividad de las lactamas tricíclicas en medio ácido: la reacción con TiCl4 en THF, proporciona lactamas insaturadas con elevada estereoselectividad y buen rendimiento. La presencia de la función enamida, nos permitió preparar selectivamente nuevas cis y trans octahidroindolonas. Esta metodología nos permitió sintetizar el (a)-Licorano, un metabolito de la familia de las Amaryllidaceae.
36
Karstens, Willem Frederik Johan. "Palladium-catalyzed cyclization reactions of allene- and acetylene-substituted lactams." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2000. http://dare.uva.nl/document/83628.
37
Houson, I. N. "Ring expansions in the synthesis of di- and tri-lactams." Thesis, University of Oxford, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.390511.
38
Rahman, Adrian. "The synthesis of new tricyclic beta lactams based upon quinoline." Thesis, University of Liverpool, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.366356.
39
Thomas, Russell John. "The synthesis of novel #beta#-lactams with potential antifungal activity." Thesis, University of Exeter, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.277147.
40
Skytte, Dorthe. "Antimalarial norneolignans, synthesis and SAR & synthesis of beta-lactams /." Cph. : Danish University of Pharmaceutical Sciences, Department of Medicinal Chemistry, 2005. http://www.dfuni.dk/index.php/Dorthe_Mondrup_Skytte/2238/0/.
41
André, Marcelo Fabiano 1978. "Sintese de B-piperonil-y-butirolactona e B-lactamas utilizando reações de Morita-Baylis-Hillman." [s.n.], 2009. http://repositorio.unicamp.br/jspui/handle/REPOSIP/250241.
Abstract:
Orientador: Fernando Antonio Santos CoelhoDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Quimica
Made available in DSpace on 2018-08-14T14:24:10Z (GMT). No. of bitstreams: 1 Andre_MarceloFabiano_M.pdf: 7456902 bytes, checksum: 8a8b77c97023eb4ce17c25791c0a18f8 (MD5) Previous issue date: 2009
Resumo: As b-piperonil-g-butirolactonas são intermediários importantes, tendo em vista que a partir delas é possível dar origem a uma série de lignanas, classe de substâncias de grande interesse científico, por apresentarem diversas atividades biológicas, tais como: antiretroviral, antitumoral, antimalárica, entre outras. Neste trabalho realizamos estudos visando melhorar a diastereosseletividade na preparação de g-butirolactonas com estereoquímica relativa trans, já que a cis já era preparada com boa diastereosseletividade em nosso laboratório. A metodologia desenvolvida baseia-se na redução de um b-ceto-éster obtido a partir da oxidação de um a-ciano-metil-b-hidroxi-éster, este último obtido com um bom rendimento a partir de uma reação de adição de Michael sobre um aduto de Morita-Baylis-Hillman ( MBH). Na segunda parte do trabalho preparamos b-amino-ésteres a partir dos adutos de Morita-Baylis- Hillman (MBH). Utilizamos como estratégia uma reação de adição do tipo Michael com várias aminas. Os b-amino-ésteres foram obtidos com rendimentos variando de 78-93%. Os produtos foram caracterizados e a estereoquímica relativa foi determinada, por nOe, através da formação de um intermediário oxazinanona. Esses b-amino-ésteres são importantes intermediários para a síntese de heterociclos, tais como b-lactamas e oxazinanonas funcionalizadas.
Abstract: The b-piperonil-g-butirolactones are important synthetic intermediates, since they can be used as substrates for the synthesis of different type of lignans, a class of substances of great scientific interest. Lignans exhibit relevant biological activites, as anti-tumoral, anti-retroviral, anti-malarial, etc. In this work, studies have been carried out aiming at improving the diastereoselectivity for the preaparation of butirolactones having anti relative stereochemistry. A method to synthesize g-butirolactone have already been established in our laboratory. The methodology used was based on the the stereoselective reduction of a b-ketoester prepared from the oxidation of a a-cyanomethyl-b-hydroxy-ester. The latter was promptly prepared, in good yields, from a cyanide 1,4 addition over the double bond of Morita-Baylis-Hillman (MBH) adducts. In the second part of this work, we have prepared several b-amino-esters from Morita-Baylis- Hillman (MBH) adducts. The strategy was based also on a Michael addition of different amines over the double bond of MBH adducts. The b-amino-esters were obtained in good yield. Their stereochemistries were determined by nOe experiments of the corresponding oxazinanones. These b-amino-esters are important intermediates for the synthesis of heterocycles, as b-lactams and functionalized oxazinanones.
Mestrado
Quimica Organica
Mestre em Química
42
Bhattacharya, Biplob. "Synthesis and Anti-MRSA Activity of Hydrophilic C3-Acylated N-Thiolated β-Lactams and N-Acyl Ciprofloxacin-N-Thiolated β-Lactam Hybrids." Scholar Commons, 2012. http://scholarcommons.usf.edu/etd/4289.
Abstract:
The Turos laboratory has been working with N-thiolated β-lactams for years trying to understand the mode of action and structural features it needs to have biological activity. Over the years new data has shown promising inhibitory activity against various microbes.
In this dissertation, a review of the vast amount of work carried out on N-thiolated β-lactams in Turos laboratory has been done and their novelty, in terms of structure and mechanism has been discussed. A complete outline of our work in the discovery and ongoing development of these compounds, starting from our initial, unexpected finding of antimicrobial activity for one of the lead compounds, to a more complete understanding of their chemical and biological mode of action and potential utility as antibacterial compounds, has been provided.
Previous researches by graduate students in the Turos laboratory have shown that N-thiolated β-lactams targets Type II Fatty Acid Synthesis (FAS). In process of understanding this further, other FAS inhibiting antibiotics like Triclosan were compared to our lactams by adding excess of exogenous fatty acids. Results revealed vast differences in the MIC value of triclosan and N-thiolated β-lactams, giving an idea that there might be a different mode of action or a different target altogether.
The third chapter discusses the study of attaching hydrophilic C3 side chains like amino acids and carbohydrates on N-thiolated β-lactams while studying the influence of microbiological activity. From the study it was found that the lengthening of the side chain halts the inhibitory activity regardless of whether the side chain contains unsaturation or branching. Results showed that polar groups were not well tolerated and the inhibitory activity goes down regardless of polarity.
Finally, research on dual-action antibiotics was discussed. Antibiotics cause continuous bacterial resistance and in this aspect use of two drugs with different mode of action can call for reduction of the resistance. Herein, N-acyl ciprofloxacin and N-thiolated β-lactams were connected together via an ester linkage. Six new hybrid compounds have been synthesized successfully and tested against E. faecium, K. pneumoniae, A. baumannii, P. aeruginosa, and E. cloacae.
43
Balko, Tamara. "Characterization of the inoculum effect with Haemophilus influenzae and ß-lactams." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp04/mq23211.pdf.
44
Heaney, V. J. "The synthesis and biological activity of monocyclic beta-lactams and benzoxazinones." Thesis, Queen's University Belfast, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.354234.
45
Sykes, Nicholas Oliver. "Structure reactivity relationships of γ lactones, γ lactams and β sultams." Thesis, University of Huddersfield, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.270545.
46
Brown, Tom. "Studies on the inhibition of enzymes by boronic acids and lactams." Thesis, University of Oxford, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.670022.
47
Evans, P. Andrew. "New synthetic methodology for the preparation of monocyclic medium ring lactams." Thesis, University of Cambridge, 1991. https://www.repository.cam.ac.uk/handle/1810/273132.
48
Hites, Maya. "Beta-lactams in obese patients: what is the adequate dosage regimen?" Doctoral thesis, Universite Libre de Bruxelles, 2017. https://dipot.ulb.ac.be/dspace/bitstream/2013/243232/3/Table.pdf.
Abstract:
Introduction :La prévalence de l’obésité, parmi les patients hospitalisés, est en augmentation. Les patients obèses présentent un risque accru de développer des infections nosocomiales par rapport aux individus non-obèses. Parmi les antibiotiques, la classe des β-lactames est la plus utilisée à l’hôpital tant en prophylaxie chirurgicale que pour le traitement des infections. Les recommandations de doses en vigueur sont basées sur des études pharmacocinétiques (PK) effectuées chez des patients non-obèses. Cependant, les patients obèses présentent des altérations physiologiques qui pourraient théoriquement être à l’origine de modifications des paramètres PK de ces antibiotiques. L’utilisation de doses standards d’antibiotiques pourrait avoir comme conséquence des concentrations sériques inadéquates chez ces patients; elles peuvent, dès lors, conduire à des échecs thérapeutiques et/ou favoriser l’émergence de souches résistantes. Objectifs: Ce travail de thèse a pour but d’approfondir les connaissances sur la PK des β-lactames chez les patients obèses présentant des scores de sévérité clinique différents. Patients et Méthodes: Quatre études PK ont été réalisées chez les patients obèses :1) une étude prospective de patients obèses, et non-obèses, ayant reçu de la céfazoline (CFZ) en prophylaxie de chirurgie digestive, 2) une étude préliminaire, prospective incluant uniquement des patients obèses traités pour des infections non sévères par l’un des 4 β-lactames à large spectre (pipéracilline-tazobactam (TZP), ceftazidime/céfépime (CEF), et méropénem (MEM)), 3) une étude prospective, avec groupe contrôle de patients non-obèses, étudiant la PK du TZP donné en traitement d’infections non sévères et 4) une étude rétrospective cas-témoin évaluant la PK de 4 β-lactames à large spectre (TZP, CEF, ou MEM) donnés pour le traitement d’infections sévères aux soins intensifs. Les taux sériques de ces antibiotiques ont été mesurés par chromatographie liquide et corrélés à plusieurs paramètres démographiques, biologiques et hémodynamiques. Résultats: Etude sur CFZ :Soixante-trois patients ont participé à l’étude: parmi ceux-ci, 43 avaient un index de masse corporelle (IMC) ≥ 35 kg/m2, et 22 un poids total ≥ 120 kg. Sur l’ensemble des patients, les concentrations sériques de CFZ étaient adéquates chez 100% des patients à 180 minutes (T180) et chez 64% (40/63) à 240 minutes (T240) après le début de l’infusion de CFZ. Il n’y avait pas de différence significative entre le pourcentage des patients avec des taux sériques adéquats à T240, quel que soit le paramètre utilisé pour la comparaison (IMC ≥ 35 kg/m2 versus IMC < 35 kg/m2, ou poids total ≥ 120 kg versus poids total < 120 kg). Etude préliminaire sur TZP, CEF et MEM: Cinquante-six patients obèses ont été inclus dans l’étude ;14 ont reçu du MEM, 31 du TZP et 11 du CEF. Parmi ces patients, les concentrations sériques adéquates pour traiter une infection à P. aeruginosa ont été atteintes chez 93% des patients traités par MEM, 68% des patients traités par TZP, et 73% des patients traités par CEF. Le volume de distribution (VD) et la clearance totale (CL) des β-lactames étaient augmentés par rapport à des valeurs rapportées dans la littérature chez les patients non-obèses. En effet, plus de 25% des patients présentaient une clearance en créatinine (CrCl) mesurée supérieure à 150 ml/minute, ce facteur étant identifié comme facteur de risque de concentrations sériques insuffisantes. Etude sur TZP: Trente-deux patients (14 non-obèses et 18 obèses) ont été inclus dans l’étude et ont reçu les doses standards de TZP. Une augmentation du VD (25.4 ± 5.6L vs. 21.0 ± 3.9 L, p= 0.018) et de la CL (18.1 ± 4.7 vs. 13.5 ± 40.1, p= 0.007) a été observé chez les patients obèses par rapport aux non-obèses conduisant à des concentrations statistiquement inférieures de TZP libre par rapport aux patients non-obèses. De même, malgré des valeurs de créatinine sérique semblables (0.8 ± 0.3 versus 0.9 ± 0.3 mg/dl, p=0.26), la CrCl mesurée sur des urines de 24h, était significativement plus élévée chez les obèses par rapport aux non-obèses (128 ± 58 vs. 79 ± 26 ml/min, p=0.006). Etude rétrospective cas-témoin sur TZP, CEF, et MEM aux soins intensifs: Quarante-neuf patients obèses et 59 patients non-obèses ont été inclus. Soixante-huit monitoring thérapeutiques ont été effectués chez les patients obèses et comparés à 68 monitoring thérapeutiques effectués chez les patients non-obèses. Après administration des doses standards des β-lactames, 1/3 des patients obèses avait des concentrations sériques insuffisantes pour traiter des infections à P. aeruginosa, et 1/4 de ces patients avait des concentrations sériques excessives, potentiellement toxiques. Par contre, aucune différence statistiquement significative n’a été observée entre les concentrations sériques des β-lactames des patients obèses et non-obèses. Conclusions :Lors de la prophylaxie chirurgicale, l’administration des doses standards de CFZ a montré des concentrations sériques insuffisantes pour assurer une couverture prophylactique adéquate en cas d’intervention chirugicale d’une durée supérieure à 180 minutes. Ni le poids total, ni l’IMC n’a pu identifier les patients qui nécessiteront une dose plus élevée de CFZ. De même, les doses standards des β-lactames à large spectre se sont avérées insuffisantes dans le traitement des infections non sévères et sévères dues à P. aeruginosa chez les patients obèses. En cas d’infections peu sévères, les concentrations sériques, chez ces patients, étaient significativement moindres que chez les patients non-obèses ;ceci étant lié à une augmentation du VD et de la CL des β-lactames. Un facteur de risque majeur retrouvé était une CrCl augmentée chez les patients obèses. Chez les patients avec infections sévères, la PK des β-lactames n’était par contre pas significativement différente entre les patients obèses et non-obèses. Ceci probablement à cause des perturbations déjà importantes de la PK des β-lactames liées à la séverité du sepsis. En conclusion, ces études identifient des perturbations de la PK des β-lactames chez les patients obèses. Parmi celles-ci, l’augmentation de la clearance rénale est un élement déterminant dans l’inadéquation des concentrations sériques. La situation est plus complexe chez les patients obèses aux soins intensifs où d’autres facteurs peuvent encore s’associer et perturber la PK des β-lactames.Doctorat en Sciences médicales (Médecine)
info:eu-repo/semantics/nonPublished
49
Jandaghi, Morteza. "Alkylaluminophosphonate Catalysts for Ring-Opening Polymerization of Lactones, Lactams, and Lactides." University of Toledo / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1588957446076538.
50
Prando, Alessandra 1980. "Estudos sintéticos para a preparação de derivados lactâmicos = uso do ácido quínico." [s.n.], 2007. http://repositorio.unicamp.br/jspui/handle/REPOSIP/248440.
Abstract:
Orientador: Lúcia Helena Brito BaptistellaDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Química
Made available in DSpace on 2018-08-16T21:00:20Z (GMT). No. of bitstreams: 1 Prando_Alessandra_M.pdf: 6403729 bytes, checksum: ad4c9b72f3570ace54e72daf35771fac (MD5) Previous issue date: 2007
Resumo: As lactamas, de um modo geral, são de bastante interesse como alvos sintéticos, pois podem apresentar ampla variedade de funções em substratos biológicos. Este trabalho teve como objetivo a preparação de heterociclos nitrogenados, no caso lactamas, a partir do ácido quínico 1. Estas seriam inéditas e, além disso, não existem descrições na literatura de preparação de lactamas a partir do ácido quínico. A rota proposta sugere a introdução do nitrogênio via uma aminólise assistida por microondas, após manipulações químicas no grupo carboxílico inicial. A hidroxiamida formada, aqui representada como 3, foi utilizada para reações visando a formação das lactamas 4 e 7, que seriam provenientes de uma ciclização intramolecular utilizando o nitrogênio da amida como nucleófilo em reação de SN2. Com a introdução da função nitrogenada, duas seqüências sintéticas foram exploradas visando a reação de ciclização intramolecular: uma utilizando o C3 do ácido quínico como centro eletrofílico, que levaria a 4, e a outra utilizando o C5, que levaria a 7. Para uma ciclização em C3, vários testes foram realizados, mas para se chegar a um bom grupo abandonador nesta posição os resultados não foram satisfatórios. Para uma ciclização em C5 foi necessário primeiramente a inversão da estereoquímica neste centro e os melhores resultados foram obtidos via uma seqüência oxidação-redução. Após introdução de um grupo abandonador nesta posição, tratamento em meio básico levou à formação da lactama almejada. A seqüência proposta pode abrir novas alternativas para a preparação de outras lactamas e também de derivados das 4-hidroxiprolinas inéditos.
Abstract: The lactams are very interesting as synthetic targets, especially because they can show a wide variety of functions on biological substrates. This work aimed the preparation of nitrogen heterocycles, in this case lactams, from quinic acid. Their structures are unprecedented, and to the best of our knowledge, there are no reports of the preparation of lactamas from quinic acid in the literature The proposed plan suggests the introduction of the nitrogen via an aminolyses reaction assisted by microwaves of an advanced intermediate. The hydroxyamide formed, here represented as 3, was used for reactions aiming the formation of the lactams skeletons 4 and 7, which would be obtained from an intramolecular using the nitrogen of the amide group as a nucleophile on a SN2 reaction. After the introduction of nitrogenated function, two synthetic sequences were explored aiming the intramolecular cyclisation reaction: one using the C3 of quinic acid as an electrophilic center, which would lead to 4, and other using the C5, which would lead to 7. In order to make the cyclisation reaction on C3, several tests were performed but the results were not satisfactory. On the other hand, for the cyclisation on C5, it was necessary, first of all, the stereochemical inversion in this center, and best results were achieved by an oxidation-reduction sequence. After the introduction of a leaving group in this position, treatment using base led the formation of desired lactam. The proposed sequence should open new alternatives for the preparation of other lactams and also new derivatives of 4-hidroxiprolines.
Mestrado
Quimica Organica
Mestre em Química