Dissertations / Theses on the topic 'Total synthesis of GA18'
To see the other types of publications on this topic, follow the link: Total synthesis of GA18.
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 'Total synthesis of GA18.'
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
Watson, Christine Anne Louise. "Total synthesis of bistheonellic acid B/ total synthesis of scytophycin C." Thesis, University of Cambridge, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.627216.
Full text
2
Chan, Bryan Ka Ip. "Total synthesis of streptonigrone." Thesis, University of British Columbia, 2007. http://hdl.handle.net/2429/31581.
Full textAbstract:
This thesis describes the total synthesis of streptonigrone. The centerpiece of our route to the target molecule is a facile one-pot construction of 3-alkylpyridones developed in our laboratory. The quinoline segment of the target molecule, prepared through a Conrad-Limpach synthesis, was condensed with 2-benzyloxy-3,4-dimethoxybenzaldehyde to afford a chalcone intermediate suitable for our pyridine-forming reaction. The assembly of the central 3-methylpyridone ring of the natural product was then accomplished through the merger of the chalcone with 2-cyanopropanamide. Functionalization of the pyridone was then completed through an anionic sequence.Science, Faculty of
Chemistry, Department of
Graduate
3
Shelton, Ruth E. "Total synthesis of peduncularine." Thesis, University of Oxford, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.526451.
Full text
4
Sparling, Brian Andrew. "Total Synthesis of Hyperforin." Thesis, Harvard University, 2013. http://dissertations.umi.com/gsas.harvard:11098.
Full textAbstract:
Hyperforin is the component of the medicinal herb St. John's Wort (Hypericum perforatum) responsible for its antidepressant activity. It works by blocking the reuptake of a variety of neurotransmitters through a unique mechanism of action and may be a critical lead for the treatment of depression and possibly other human diseases. However, the therapeutic potential of hyperforin is severely handicapped by its poor water solubility, facile oxidative degradation, and potent activation of pregnane X receptor, leading to increased expression of many genes involved in xenobiotic metabolism. Access to a wide variety of hyperforin analogs is critical for mitigating these shortcomings while maintaining therapeutic activity. While limited semisynthetic manipulation of isolated hyperforin is feasible, total synthesis is the only possible means of obtaining diverse hyperforin analogs.Chemistry and Chemical Biology
5
Baldwin, Ian Robert. "Total synthesis of acetoxyodontoschismenol." Thesis, University of Southampton, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.284653.
Full text
6
Chen, Cheng Yi. "Total synthesis of (+)-stenine /." The Ohio State University, 1990. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487684245465948.
Full text
7
Li, Fang. "Total Synthesis of (-)-Acutumine." BYU ScholarsArchive, 2009. https://scholarsarchive.byu.edu/etd/2193.
Full textAbstract:
Acutumine is a tetracyclic alkaloid isolated from the Asian vine Menispermum dauricum with selective T-cell cytotoxicity and antiamnestic properties. We have developed a total synthetic route to this congested alkaloid, during which we also found a novel, stereoselective radical-crossover reaction that combines an intramolecular radical conjugate addition with a subsequent enolate hydroxylation. Key features of this synthesis also include a reagent-controlled diastereoselective ketone allylation, an anionic oxy-Cope rearrangement to form a congested quaternary sterocenter, a pyridine-mediated selective ozonolysis, and a Lewis acid promoted Michael-type cyclization.
8
Shamim, Khalida. "I. Total synthesis of stemonine. II. Studies towards the total synthesis of kendomycin." [Bloomington, Ind.] : Indiana University, 2006. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3243781.
Full textAbstract:
Thesis (Ph. D.)--Indiana University, Dept. of Chemistry, 2006.Title from PDF t.p. (viewed Nov. 18, 2008). Source: Dissertation Abstracts International, Volume: 67-12, Section: B, page: 7099. Adviser: David R. Williams.
9
Liu, Qingsong. "Large scale total synthesis of apoptolidinone and progress towards the total synthesis of ammocidin." [College Station, Tex. : Texas A&M University, 2006. http://hdl.handle.net/1969.1/ETD-TAMU-1054.
Full text
10
Zhang, Yan Crimmins Michael T. "Total synthesis of (-)-mucocin and studies toward the asymmetric total synthesis of brianthein A." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2007. http://dc.lib.unc.edu/u?/etd,1414.
Full textAbstract:
Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2007.Title from electronic title page (viewed Apr. 25, 2008). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Chemistry." Discipline: Chemistry; Department/School: Chemistry.
11
Hassan, Haitham. "Total synthesis of eucophylline : a free-radical approach towards total synthesis of cytotoxic leucophyllidine." Thesis, Bordeaux, 2016. http://www.theses.fr/2016BORD0153/document.
Full textAbstract:
La thèse décrit la première synthèse totale de l'Eucophylline, le fragment sud de l'alcaloïde Leucophyllidine récemment isolé à partir de Leuconotisgriffithii et L. eugenifolius. La synthèse en 10 étapes comprend une nouvelle méthode d’accès au squelette azabicyclo[3.3.1]nonane par un processus de carbooximation radicalaire d'oléfines à trois composants. Au cours de ces études, nous avons également isolé des énamines présentant des stabilités inhabituelles résultant de leur conformation bicyclique tendue. La synthèse de la partie éburnane, le fragment nord de la Leucophyllidine, a été réalisée grâce à une nouvelle réaction radicalaire de carbo-cyanation à trois composants. Cette réaction radicalaire s'est révélée efficace pour installer le groupement fonctionnel nitrile sur des oléfines, et éventuellement former des centres quaternaires, notamment dans des structures complexes, puisqu'une bonne tolérance aux différents groupes fonctionnels a été observée. Le couplage biomimétique entre le squelette éburnane et l'Eucophylline a finalement été étudié en utilisant des modèles de structure similaire. Les résultats préliminaires de cette étude ont montré que l'absence d'effet gem-diméthyle dans le modèle éburnane empêche probablement la formation de l'imine cyclique,intermédiaire-clé dans le couplage désiréThe thesis describes the first total synthesis of Eucophylline, the south fragment of the Leucophyllidine alkaloid recently isolated from Leuconotis griffithiiand L. eugenifolius. The 10-step synthesis encompasses a new straight forward method to access to the azabicyclo[3.3.1]nonane skeleton through a free-radical three-component olefinic carbo-oximation process. During these studies, we also isolated enamines exhibiting unusual stabilities resulting from their strained bicyclicconformation. The synthesis of the Eburnane part, the north fragment of Leucophyllidine, was developed relying on a new free-radical three-component Carbo-Cyanation reaction. This new reaction showed high tolerance toward different functional groups and provided an efficient mean to install the nitrile group in complex structures and to introduce quaternary centers. The biomimetic coupling between the Eburnane and Eucophylline fragments was finally studied using structurally similar models. Preliminary results of this model study showed that absence of a gemdimethyleffect in the Eburnane model probably prevents the formation of the cyclicimine, key intermediate for the desired coupling
12
Ballette, Roberto. "Total synthesis of (+)-Madangamine D." Doctoral thesis, Universitat de Barcelona, 2014. http://hdl.handle.net/10803/145559.
Full textAbstract:
Madangamines are a small group of marine alkaloids isolated from sponges of the order Haplosclerida collected by hand using scuba on reefs off Madang, Papua New Guinea.
Madangamine A show significant in vitro cytotoxicity against murine leukemia (P388), human lung (A549), brain (U373) and breast (MCF-7). However, no bioactivity data have been reported for madangamines B-E, and further pharmacological research on this alkaloid group has been prevented by the minute amount of alkaloid samples. We present herein the enantioselective synthesis of (+)-madangamine D, which represents the first total synthesis of an alkaloid of the madangamine group.
Using a phenylglycinol-derived bicyclic lactam as the starting enantiomeric scaffold we were able to control the stereochemistry of all three contiguous stereogenic centers on the BC ring system, while A ring was formed through a stereocontrolled cascade aminohydroxylation reaction, in which an “in situ generated” amine attacks an epoxide ring. This strategy provides a direct route to the diazatricyclic ABC core common to all madangamines, with the appropriate functionalization to allow the subsequent building of the macrocyclic D and E rings of these alkaloids.
The saturated 14-membered D ring of madangamine D, leading to the tetracyclic ABCD system was efficiently constructed using a ring-closing metathesis reaction followed by a catalytic hydrogenation of the resulting double bond. The (Z,Z)-unsaturated 11-membered E ring, required to complete the synthesis of madangamine D was successfully assembled in a straightforward manner using a Z-stereoselective Wittig reaction followed by an intramolecular macrolactamization.
Madangamine D showed significant in vitro cytotoxic activity against human colon HT29 (GI50 4.4 µg/mL) and pancreas PSN1 (GI50 7.4 µg/mL) cancer cell lines, but was inactive against lung NSCLC A549 and breast MDA-MB-231 cancer cell lines at the highest assayed concentration (10 µg/mL).Las esponjas del orden Haplosclerida representan una importante fuente de alcaloides estructuralmente diversos pero biogenéticamente relacionados, siendo las madangaminas uno de los menos estudiados desde el punto de vista sintético. En 1994 fue aislada el primer alcaloide de este grupo, la Madangamina A de la esponja marina Xestospongia ingens1 y unos años más tarde se aislaron cuatro nuevos alcaloides, las madangaminas BE.2 Estructuralmente, las madangamines son alcaloides pentacíclicos y se caracterizan por presentar un núcleo diazatricíclico (anillos ABC) y dos puentes de carbonados. El anillo macrocíclico D es diferente en cada madangamina en tamaño, así como en el grado y la posición de insaturación, mientras que el anillo E es idéntico en todas ellas. En la presente Tesis Doctoral presentamos la síntesis enantioselectiva de ()-madangamine D,3 que ofrece por primera vez una muestra pura de este producto natural y constituye la primera síntesis total de un alcaloide de la grupo de las madangamines. Usando de una lactama bicíclica derivada del fenilglicinol como el scafold enantiomérico de partida, nuestro enfoque consiste en la construcción inicial del núcleo diazatricíclico ABC y la posterior construcción de los anillos macrocíclicos D y E. La lactama de partida 2 es fácilmente accesible por ciclocondensación de oxoester 1 con el (R)-fenilglicinol, en un proceso en donde se instala el primer estereocentro. El intermedio diazatríclico se prepara a partir de una lactama insaturada derivada de 2. En este proceso son claves una reacción de adición conjugada estereoselectiva, el cierre del anillo carbocíclico mediante metátesis, una alquilación estereoselectiva y finalmente cierre del anillo A por aminohidroxilación. La anulación de los anillos macrocíclicos se lleva a cabo mediante una reacción de cierre del anillo por metátesis (anillo D) y una olefinación de Wittig seguida de macrolactamización (anillo E). Los datos de RMN de 1H y 13C de nuestra madangamina sintética fueron coincidentes con los reportados para el producto natural. La madangamina D sintética muestra citotoxicidad in vitro contra las líneas celulares de cáncer HT29 de colon humano y PSN1 páncreas.
13
Kleinbeck, Florian Karl. "Total synthesis of bafilomycin A₁ /." Zürich : ETH, 2008. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=17777.
Full text
14
Bosch, Caroline. "Total Synthesis of Phlegmarine Alkaloids." Doctoral thesis, Universitat de Barcelona, 2016. http://hdl.handle.net/10803/399380.
Full textAbstract:
This doctoral thesis consists in two main parts. The first part focus in the study of methodology development in order to bring modularity and diversification to compounds studied within the research group. It consists first in the development of an easy procedure to access enantiopure substituted octahydroindoles relevant for natural products synthesis, then in the diversification of a common building block used for the total synthesis of phlegmarine alkaloids allowing access to unprecedented heterocyclic tetrahydrocarbazoles compounds, but most importantly in the achievement of a methodology allowing access to any phlegmarine alkaloids from a simple common precursor i.e. using a unified methodology. A stereodivergent hydrogenation route is reported in each phlegmarine alkaloid series, allowing modulation of the diastereoselectivity in key intermediates of the synthetic approach.
The second part focuses on synthetic applications of the methodology developed to allow to perform the first total synthesis of various phlegmarine alkaloids and also shed light on missassigned structures. These structure reassignments gave birth to a revised classification of the phlegmarine alkaloids and were confirmed by total synthesis using the unified methodology developed in the first part.
All of the analytical data obtained during this project led us to the establishment of general rules to determine easily the stereochemistry of any phlegmarine type alkaloids.
In summary, the first total syntheses of (+)-serratezomine E, (-)-serralongamine, (-)-huperzine K, huperzine M and (-)-huperzine N have been achieved and the usefulness of the tandem intermolecular Michael reaction/intramolecular aldol reaction and in-situ intramolecular aza-Michael process has been extended to other series of azabicyclic compounds in enantiopure form.
15
Chiba, Hiroaki. "Total Synthesis of Tetrahydroisoquinoline Alkaloids." 京都大学 (Kyoto University), 2013. http://hdl.handle.net/2433/174544.
Full text
16
Xu, Sanjia. "Formal total synthesis of (±)-tetrodotoxin." Thesis, University of British Columbia, 2016. http://hdl.handle.net/2429/59489.
Full textAbstract:
This dissertation details a formal total synthesis of (±)-tetrodotoxin, a potent sodium channel blocker, based on a transformation developed in these laboratories: the bimolecular oxidative amidation of phenols. The present route leads to the Du Bois intermediate in 27 steps from a commercial starting material. Because the Du Bois intermediate can be elaborated to tetrodotoxin in 4 steps, this work constitutes a formal synthesis of the natural product in 31 steps. This is competitive with the best known alternatives. A structural revision of the Sato tetrodotoxin intermediate is also provided. Finally, an even more concise avenue to a new bis-lactonic precursor of the natural product is described, and potential enantioselective routes to tetrodotoxin are discussed.Science, Faculty of
Chemistry, Department of
Graduate
17
Lefranc, David. "Total synthesis of micrococcin P1." Thesis, University of British Columbia, 2008. http://hdl.handle.net/2429/3626.
Full textAbstract:
This thesis describes the total synthesis of the thiopeptide antibiotic micrococcin P1.
It unambiguously elucidates its structure, which has been subject to controversy for over thirty years. The centerpiece of the route to the target molecule is a facile one-pot construction of the central thiazole/pyridine cluster developed in our laboratory. This highlyconvergent route entails a delicate Michael addition to yield a Hantzsch dihydropyridine intermediate, which undergoes further oxidation to the fully aromatised heterocycle. The synthesis was completed by the coupling of this core with a highly-modified sensitive peptide chain. The modular nature of the synthesis can also accommodate modifications for
SAR studies, contributing thereby to the fields of medicinal chemistry, pharmacology, and microbiology. At a purely chemical level, we remain confident that this work will serve as a valuable guide in the elaboration of other members of the thiopeptide family.
18
Aulakh, Virender Singh. "Total synthesis of thiocillin I." Thesis, University of British Columbia, 2010. http://hdl.handle.net/2429/29493.
Full textAbstract:
This thesis describes the first total synthesis of Thiocillin I, a thiopeptide antibiotic that is structurally similar to Micrococcin P1. Our group has recently completed the first total synthesis of the latter natural product. In that connection, new methodology had to be devised for the assembly of the central pyridine-thiazole cluster of the molecule. The present work details the development of a considerably more efficient "second generation approach" to that crucial molecular subunit. The new technique relies upon a three-component condensation to form the pyridine core with the full complement of thiazoles already in place. This transformation is recognized as a variant of the Bohlmann-Rahtz reaction that has heretofore eluded the synthetic community. Minor modification of this chemistry is likely to facilitate the synthesis of several other thiopeptide antibiotics, naturally occurring or otherwise. This presages the advent of technology for the conduct of medicinal chemistry studies of thiopeptide substances and promises to lead to new generations of chemotherapeutic resources.
19
Scutt, James Nicholas. "Total synthesis of (+)-belactosin A." Thesis, Imperial College London, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.419852.
Full text
20
Bebbington, David. "Total synthesis of hypoglycin A." Thesis, University of Oxford, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.306112.
Full text
21
Hayes, Stewart. "The total synthesis of vigulariol." Thesis, University of Nottingham, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.495554.
Full textAbstract:
(+)-Vigulariol was isolated in 2005 by Sheu and coworkers off the coast of Taiwan and belongs to the cladiellin (eunicellin) class of the 2-11 cyclised cembranoid family of natural products. Vigulariol along with numerous other members of the cladiellin family have been shown to possess interesting biological properties including cytotoxicity against various cell lines. This thesis presents the total syntheses of (±)-vigulariol and (-)-vigulariol, that were completed in 20 steps respectively in an overall yield of 4.1% and 5.9%. The key steps in the synthesis are; a samarium diiodide reductive cyclisation to furnish a 2,6-syn-5,6-anti tetrahydropyranol, oxonium ylide formation and an intermolecular Diels-Alder cycloaddition to construct the cyclohexyl ring.
22
Anderson, Regan J. "Total synthesis of variolin B." Thesis, University of Canterbury. Chemistry, 2002. http://hdl.handle.net/10092/6061.
Full textAbstract:
This thesis describes the development of methodology which has led to the total synthesis of variolin B, a marine alkaloid with potent antitumour properties. In Chapter One, a brief summary of the association of organic synthesis and marine natural products is provided. This is followed by an account of the variolin family of natural products and synthetic efforts that have been directed towards them. A new strategy is proposed that exploits the hidden symmetry in variolin B.
Chapter Two covers investigations into the synthesis of the variolin skeleton using a variety of reagent systems. A rapid entry into the core structure of the variolins was found, with the key step being a deoxygenation/cyclisation protocol, which was mediated by the combination of triethylsilane and trifluoroacetic acid. Evidence was obtained to suggest an unexpected mechanism for this reaction. Straightforward functional group manipulation led to a synthesis of deoxyvariolin B.
In Chapter Three, the previously established methodology was applied to an alternative starting material, appropriate for a synthesis of variolin B. However, the process was low-yielding and gave variable results. Some modifications to the methodology led to a reliable and efficient procedure for the synthesis of the variolin skeleton, which was subsequently transformed to variolin B. The synthesis proceeded in a total of eight linear steps, with an overall yield of 13%.
The methodology which has been developed lends itself to the production of analogues of the variolins. The synthesis and biological testing of some analogues are presented in Chapter Four, along with a discussion on the structural features which confer biological activity on variolin B.
A brief summary of the work described in this thesis and potential future studies is given in Chapter Five.
23
Brooke, Darby Gerard. "Total synthesis of hydroxystrobilurin A." Thesis, University of Canterbury. Chemistry, 2002. http://hdl.handle.net/10092/6541.
Full textAbstract:
This thesis describes the first three total syntheses of hydroxystrobilurin A, a member of the strobilurin family of fungicidal natural products which are produced by a variety of fungal species worldwide. Chapter 1 provides an account of the discovery, structure, and biological activity of the strobilurins, describes the total syntheses of strobilurins reported to date, and covers the synthetic and spectroscopic work that has been conducted on the strobilurins by other workers in this department. An overview of the use of palladium-catalysed carbon-carbon bond forming methodologies in syntheses of several natural products and strobilurin analogues is given, followed by a retro synthetic analysis of hydroxystrobilurin A which delineates two possible strategies for the synthesis of this compound based on the utilisation of such palladium-based chemistry.
Chapter 2 details investigations of these two strategies, with the diene-based route proving more successful than the enyne-based approach. Efficient diene synthesis was achieved via Stille coupling, but direct access to hydroxystrobilurin A via Stille coupling between a diene alcohol and a β-methoxyacrylate unfortunately proved impossible. The use of hydroxyl-group protection enabled the formation of two triene analogues of hydroxystrobilurin A via Stille coupling, and although one of these was found to have isomerised into a non-natural strobilurin triene system, the other possessed the correct stereochemistry and was able to be deprotected to afford a low yield of the natural product. An efficient synthesis of the triene ester analogue of hydroxystrobilurin A was developed, and this compound was reduced to give a low yield of the natural product. Access to the corresponding triene aldehyde was also established, and its reduction to hydroxystrobilurin A was slightly higher yielding, although efforts to improve the efficiency of this process were not successful. A summary of the above results is given in Chapter 3, followed by a description of several pathways by which future workers may be able to achieve a more efficient synthesis of hydroxystrobilurin A.
Chapter 4 describes preliminary results from the application of the palladium-catalysed carbon-carbon bond-forming techniques described in Chapter 2 to synthetic approaches towards 9-methoxystrobilurins A and K & phomoidrides A and B.
24
Beiger, Jason James. "Total Synthesis of Aflastatin A." Thesis, Harvard University, 2013. http://dissertations.umi.com/gsas.harvard:11040.
Full textAbstract:
The syntheses of aflastatin A and its C3-C48 degradation fragment are described. The syntheses feature several complex diastereoselective fragment couplings, including a C35-C36 anti-Felkin-selective boron-mediated oxygenated aldol reaction, a C15-C16 Felkin-selective trityl-catalyzed Mukaiyama aldol reaction, and a C26-C27 chelate-controlled aldol reaction involving soft enolization with magnesium. Careful comparison of the spectroscopic data for the synthetic aflastatin A C3–C48 degradation fragment (2) to that reported by the isolation group revealed a structural misassignment in the lactol region of the naturally derived degradation product. The cause of the mismatch was initially believed to be stereochemical in origin. Ultimately, the data reported for the naturally derived aflastatin A C3–C48 degradation lactol (2, R = H) was attributed to its derivative lactol trideuteriomethyl ether \((R = CD_3)\). Further, the absolute configurations of six stereogenic centers (C8, C9 and C28–C31) in aflastatin A (1) were formally revised by the isolation group prior to completion of its total synthesis. The synthesis of the aflastatin A C3–C48 lactol trideuteriomethyl ether and its spectroscopic match to the naturally derived C3–C48 degradation fragment confirm the stereochemical revision. The synthesis of a degradation product containing the tetramic acid and two overlapping stereocenters (C4 and C6) was also achieved. Its spectroscopic match to the corresponding naturally derived degradation fragment verified the absolute configuration of the aflastatin A C5' stereocenter. When combined with previous degradation fragment syntheses, and eventually the total synthesis of aflastatin A, the revised stereochemical assignment of aflastatin A was fully affirmed.Chemistry and Chemical Biology
25
George, Ian R. "The total synthesis of lodopyridone." Thesis, University of Nottingham, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.663246.
Full textAbstract:
Natural products are an important and diverse class of compounds; pyrones and pyridones, examples of their chemistry and natural products featuring these structures are discussed. Lodopyridone (75) is introduced as both a highly unusual natural product and a potential NQ02 inhibitor. A number of simple lodopyridone inspired analogues were prepared as potential NQ02 inhibitors and tested for binding to the enzyme. Synthetic studies toward lodopyridone featuring acetylation, rearrangement and cross coupling approaches to the key C-6 C-C bond formation were explored. Pyrone 175 was prepared by Suzuki coupling and oxidation studies towards amide 189, featuring a key modified Corey-Ganem-Gilman reaction were explored. The key pryone 189 was converted to the pyridone 196 and manipulation to complete the synthesis of lodopyridone (75) was achieved. Studies towards the related pyridone containing natural product antibiotic B 90063 were performed and a synthetic strategy presented. Conclusion in Chapter 3 and future work in Chapter 4 is presented followed by full experimental procedures in Chapter 5.
26
Lineswala, Jayana P. "Total synthesis of lavendamycin amides." Virtual Press, 1996. http://liblink.bsu.edu/uhtbin/catkey/1036197.
Full textAbstract:
The synthesis of 7-N-acetyldemethyllavendamycin butyl amide (47), 7-Nacetyldemethyllavendamycin isopropyl amide (48), 7-N-acetyldemethyllavendamycin amide of piperidine (49), 7-N-acetyldemethyllavendamycin amide of pyrrolidine (50), 7N-acetyldemethyllavendamycin amide of morpholine (51), demethyllavendamycin butyl amide (52), demethyllavendamycin amide of pyrrolidine (53), and demethyllavendamycin amide of morpholine (54) are described. Pictet Spengler condesation of 7-acetamido-2formylquinoline-5,8-dione (28) with tryptophan butyl amide (66), tryptophan isopropyl amide (67), tryptophan amide of piperidine (68), tryptophan amide of pyrrolidine (69), and tryptophan amide of morpholine (70) in an anisole - pyridine solution directly afforded the five lavendamycin amides 47-51. Compounds 52, 53, and 54 were obtained by hydrolysis of 47, 50, and 51 with 70% H2SO4-H20 solution.Aldehyde 28 was prepared according to the following general procedure.Nitration of 8-hydroxy-2-methylquinoline (30) yielded 8-hydroxy-2-methyl-5,7 dinitroquinoline (31). Compound 31 was then hydrogenated and acylated with acetic anhydride to yield 5,7-diacetamido-2-methyl-8-acetoxyquinoline (33). Compound 33 was oxidized by potassium dichromate to give 7-acetamido-2-methylquinoline-5,8-dione (27). Treatment of 27 with selenium dioxide in refluxing 1,4-dioxane afforded compound 28.Compounds 66, 67, 68, 69, and 70 were synthesized from compounds 61,62, 63, 64, and 65. These compounds were deprotected with ammonium formate in the presence of 10% Palladium on charcoal in methanol under an argon balloon at atmospheric pressure.Compounds 61, 62, 63, 64, and 65 were obtained from 58 with butylamine, isopropylamine, piperidine, pyrrolidine, and morpholine respectively in the presence of triethylamine under an argon balloon at atmospheric pressure.Compound 58 was synthesized by the reaction of N-carbobenzyloxytryptophan, with N-hydroxy succinimide, in the presence of N-dicyclohexylcarbodimide in dried and distilled dioxane under an argon balloon at atmospheric pressure.The structures of the novel compounds 58, 47, 48, 49, 50, 51, 52, 53, and 54 were confirmed by 1H NMR, IR, EIMS, and HRMS.The structures of protected and deprotected amides 61, 62, 63, 64, 65, 66, 67, 68, 69, and 70 were also confirmed by 1 H NMR and IR spectroscopy.Department of Chemistry
27
Stocksdale, Mark G. "Total synthesis of lavendamycin analogs." Virtual Press, 1992. http://liblink.bsu.edu/uhtbin/catkey/834647.
Full textAbstract:
The syntheses of 7-N-chloroacetyllavendamycin methyl ester (55), 7-N-butyryllavendamycin methyl ester (56), 7-N-chloroacetyldemethyllavendamycin octyl ester (57), 7-N-butyryldemethyllavendamycin octyl ester (58), 7-N-chloroacetyldemethyllavendamycin isoamyl ester (59), and 7-N-butyryldemethyllavendamycin isoamyl ester (61) are described. Incorporation of the Pictet-Spengler condensation of 7-chloroacetamido-2-formylquinoline-5,8-dione (62) or 7butyramido-2-formylquinoline-5,8-dione (63) with B - methyltryptophan methyl ester (11), L-tryptophan octyl ester (64), or L-tryptophan isoamyl ester (65) in xylene directly afforded six lavendamycin analogs.The aldehydes 62 and 63 were prepared according to the following general procedure. Nitration of 8-hydroxy-2methylquinoline (66) yielded 8-hydroxy-2-methyl-5,772, and 73 are also included. 1H NMR and IR are provided compounds 67, and 71, and 1H NMR is provided for compound dinitroquinoline (67). Compound 67 was then hydrogenated and acylated with chloroacetic anhydride (or butyric anhydride) to yield 5,7-bis(chloroacet4mido)-8-hydroxy-2-methylquinoline (69) (or 5,7-dibutyramido-8-butyroxy-2 methylquinoline (71)).Compound 69 (and 71) was oxidized by potassium dichromate to give the corresponding 5,8-dione 70 (and 72). Treatment of 70 (and 72) with selenium dioxide in refluxing 1,4-dioxane afforded compound 62 (and 63). It was also noted that 71 would hydrolyze to its 8-hydroxy derivative 73 in hot methanol-water.Compound 64 was prepared through the neutralization of Ltryptophan octyl ester hydrochloride with a 14 % ammonium hydroxide solution followed by extraction. Compound 65 was synthesized via a Fischer esterification of L-tryptophan with isoamyl alcohol saturated with hydrogen chloride. The synthesis of H-methyltryptophan (44) was accomplished with the method of Snyder and Matteson.The structures of the novel compounds 55, 56, 57, 58, 59, 60, 62, 63, 69, 70, 72 and 73 were confirmed through 1H NMR, IR, EIMS, and HRMS. Elemental analyses of 62, 63, 69, 70,for 44.Department of Chemistry
28
Olang, Fatemeh. "Total synthesis of lavendamycin analogs." Virtual Press, 1995. http://liblink.bsu.edu/uhtbin/catkey/958797.
Full textAbstract:
The synthesis of 7-N -furoyllavendamycin methyl ester (35), 7-N -furoyl demethyllavendamycin methyl ester (36), 7-N -furoyldemethyllavendamycin ethyl ester (37), 7-N -furoyldemethyllavendamycin propyl ester (38), 7-N -furoyl demethyl lavendamycin butyl ester (39), 7-N -furoyldemethyllavendamycin isoamyl ester (40),7-N -furoyldemethyllavendamycin cyclohexyl ester (41), 7-N -furoyldemethyl lavendamycin octyl ester (42), 7-N -furoyldecarboxydemethyllavendamycin (43), and demethyl lavendamycin isoamyl ester (44) are described. Pictet-Spengler condensation of 7-furoylamino-2-formylquinoline-5, 8-dione (55) with (3-methyltryptophan methyl ester (4), Ltryptophan methyl ester (56), L-tryptophan ethyl ester (57), L-tryptophan propyl ester (58), L-tryptophan butyl ester (59), L-tryptophan isoamyl ester (60), L-tryptophan cyclohexyl ester (61), L-tryptophan octyl ester (62), L-tryptamine (63), in xylene, or anisole afforded ten lavendamycin analogs.Aldehyde 55 was prepared according to the following general procedure.Nitration of 8-hydroxy-2-methylquinoline (30) gave 8-hydroxy-2-methyl-5,7dinitroquinoline (31). Compound 31 was then hydrogenated and acylated with 2-furoyl chloride (or acetic anhydride ) to yield 5,7-difuroylamino-8-hydroxy-2-methylquinoline (53) or 5,7-diacetamino-8-acetoxy-2-methyl- quinoline (33). Compounds 53 and 33 were oxidized by potassium dichromate to give the corresponding 5,8-diones 54, and 27. Treatment of 53, and 27 with selenium dioxide in refluxing wet dioxane afforded compounds 55 and 28.Compound 4 was previously prepared by other members of our group, compounds 56, 57, 59, and 62 were obtained through the neutralization of the corresponding Ltryptophan ester hydrochlorides with a 14% ammonium hydroxide solution followed by extraction. Compounds 58, 60, 61 were synthesized via a Fischer esterification of Ltryptophan with : propyl alcohol, isoamyl alcohol, and cyclohexyl alcohol saturated with hydrogen chloride.The structures of compounds 53, 54, 55, 35, 36, 37, 38, 39, 40, 41, 42, 43, and 44 were confirmed through 1H NMR, IR, EIMS, and HRMS. Elemental analyses of 53, 54, and 55 are also included.The structures of esters 56, 57, 58, 59, 60, 61, 62, and 63 were confirmed by 1H NMR.Department of Chemistry
29
Stonehouse, Jeffrey Paul. "Total synthesis of (+)-rhizoxin D." Thesis, University of Nottingham, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.395458.
Full text
30
Martin, Bruce John. "A total synthesis of myxothiazol." Thesis, University of Nottingham, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.283643.
Full text
31
Sherlock, Alexandra. "A total synthesis of (+)-lactacystin." Thesis, University of Nottingham, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.431860.
Full text
32
Oehlrich, Daniel. "Total synthesis of luminacin D." Thesis, University of Warwick, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.412862.
Full text
33
Tometzki, G. B. "d1-Progesterone : A total synthesis." Thesis, University of Manchester, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.374578.
Full text
34
Kay, Claire-Louise. "The total synthesis of membrarollin." Thesis, University of Southampton, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.438693.
Full text
35
Russell, M. A. "Total synthesis of the nikkomycins." Thesis, Imperial College London, 1985. http://hdl.handle.net/10044/1/37839.
Full text
36
Broughton, Howard Barff. "A total synthesis of showdomycin." Thesis, Imperial College London, 1985. http://hdl.handle.net/10044/1/37646.
Full text
37
Saint-Dizier, François. "The total synthesis of concavine." Thesis, University of Birmingham, 2016. http://etheses.bham.ac.uk//id/eprint/7135/.
Full textAbstract:
Concavine, a diterpene natural product was isolated from a strain of Clilocybe concava in 2005 and was the first diterpene alkaloid to be isolated from a mushroom. Chapter 1 presents the unprecedented core structure of this novel alkaloid consisting of a bicyclo(3.2.1)octane system linked with a oxazepane ring. Our retrosynthetic analysis highlighting the challenges for the synthesis of concavine is presented. Chapter 2 discusses the formation of the bicyclo [3.2.1]octane system and the installation of an oxazepane ring precursor. The different strategies used to form the five-membered ring and the regioselectivity issues surrounding the addition of the oxazepane ring precursor are discussed. The completion of the core structure of concavine and the end game is described in Chapter 3. While the strategy to use a sulfone group as a ketone precursor was not successful, the hydrolysis of a vinyl sulfide group was key to access the desired ketone and complete the total synthesis of concavine. In Chapter 4 the comparison between the reported data for concavine and our synthesised compound is described. The synthesis of a new epimer was undertaken to solve the mismatch in the data without success. Both the HCI and AcOH salts ofthe synthesised concavine were formed to investigate the impact of a protonated amine on the chemical shift compared to the free amine. A summary of the total synthesis of concavine is presented in Chapter 5. The successful sequence for the formation of concavine from the commercially available anhydride and the work to match the data with the reported natural product is summarised.
38
Straub, Julie Ann. "The total synthesis of carbohydrates." Thesis, Massachusetts Institute of Technology, 1987. http://hdl.handle.net/1721.1/14622.
Full text
39
Buttler, Thomas. "A total synthesis of (+/-)-sparteine." Thesis, University of Cambridge, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.616083.
Full text
40
Florence, Gordon John. "The total synthesis of (+)-discodermolide." Thesis, University of Cambridge, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.621038.
Full text
41
Botha, Marc Edgar. "The total synthesis of aristolindiquinone." Master's thesis, University of Cape Town, 1986. http://hdl.handle.net/11427/22134.
Full textAbstract:
Bibliography: pages 97-99.Aristolindiquinone (1), a novel natural compound possibly: possessing anti-fertility activity, was synthesized via two independent routes. First, a Stobbe reaction unambiguously gave the naphthalene nucleus with the required substitution pattern (3,8-dioxygenated-2,5-dimethyl naphthalene), starting from 2-hydroxy-5-methylbenzaldehyde (31). Second, a general synthesis, of substituted C-5 oxygenated- 1,4-naphthoquinones is applied to the synthesis of (1). The critical step in the synthesis is the reaction of the novel Diels-Alder partners, dienophile (90), synthesized from 2,6-dihydroxytoluene (56), and diene (109).
42
Hong, Won-Pyo. "Total synthesis of (±)-lythrancepine-II /." The Ohio State University, 1985. http://rave.ohiolink.edu/etdc/view?acc_num=osu148726191911152.
Full text
43
Lai, Chin-Shan. "Total synthesis of axane sesquiterpenoids /." The Ohio State University, 1991. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487758680163008.
Full text
44
Kennedy, Robert M. "A total synthesis of aphidicolin." Diss., Virginia Polytechnic Institute and State University, 1985. http://hdl.handle.net/10919/54307.
Full textAbstract:
A formal total synthesis of aphidicolin, an important antitumor agent, has been accomplished. Completion of this synthesis required the development of novel methodology. Virtually all of the previous syntheses of aphidicolin share a common difficulty in the construction of the C-9 and C-10 vicinal quaternary centers. In order to solve this problem an investigation into the Michael reaction was launched.
This study has revealed that steric encumbrance may be overcome by electronic activation of the acceptor. In fact, two withdrawing substituents were found to make possible the addition of the kinetic enolates of cyclohexenones to β, β-disubstituted acceptors. Several combinations of carboethoxy, cyano, and sulfinyl substituents were utilized. Also, use of sulfinyl butenolides as acceptors demonstrated that considerable stereochemical control may be exercised over the Michael reaction.
In addition to work on the Michael reaction, the utility of a novel annulation procedure was demonstrated in the one-pot construction of the AB rings of aphidicolin. The required desulfurization of an α-sulfinyl lactone in the presence of an enone resulted in the development of a new, mild desulfurization agent. Some difficulty was encountered in the dissolving metal reduction of the A ring enone to provide the required trans decalin stereochemistry of the AB ring system of aphidicolin. However, this problem was solved by the construction of the D ring of aphidicolin prior to the dissolving metal reduction.
This work resulted in the synthesis of an intermediate in Corey's total synthesis of aphidicolin. This synthesis is approximately 15 steps long, which is competitive with the shortest reported synthesis of aphidicolin. Furthermore, this synthesis is the most efficient reported to date, providing the natural product in approximately 10% overall yield.Ph. D.
45
Liu, Yong-Peng. "Total Synthesis of Microsclerodermin D." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASF024.
Full textAbstract:
La microsclerodermine D est un peptide macrocyclique d’origine marine qui comporte six amino acides, dont deux sont disponibles commercialement : la glycine (Gly) et la sarcosine (Sar). Les quatre autres amino acides : l’acide (R)-γ-amino-β-hydroxybutyrique (GABOB), le D-6-chlorotryptophane (6-Cl-Trp), un β-amino acide polyhydroxylé (APTO) et l’acide 3-amino-4-hydroxypyrrolidinoacetique (PyrrAA) seront préparés via de nouvelles voies de synthèse. Notre objectif est de développer une voie de synthèse de la microsclerodermine D modulable et qui permettrait la synthèse d’autres membres de la famille des microsclerodermines et d’analogues. Nos nous intéresserons également à de potentielles études permettant d’évaluer leurs propriétés biologiques et leur potentiel en tant qu’agent anticancéreuxMicrosclerodermin D is a macrocyclic peptide of marine origin which contains six amino acids, of which two are commercially available: glycine (Gly) and sarcosine (Sar). The four other amino acids: (R)-γ-amino-β-hydroxybutyric acid (GABOB), D-6-chlorotryptophan (6-Cl-Trp), a polyhydroxylated β-amino acid (APTO) and 3-amino-4-hydroxypyrrolidinoacetic acid (PyrrAA) will be accessible by new synthetic routes. Our goal is to develop a modular synthetic route to microsclerodermin D that could be applicable for the preparation of other microsclerodermin family members and analogues thereof. We are also looking forward to make some investigations on their biological activities or potential as anticancer drug
46
Morris, Joanne Charleen. "The total synthesis of chamuvarinin." Thesis, University of St Andrews, 2013. http://hdl.handle.net/10023/4114.
Full textAbstract:
In 2004, the polyketide natural product, chamuvarinin (72) was isolated by Laurens et al. from the roots of Uvaria chamae, a member of the Annonaceae plant family. This unique tetrahydropyran containing acetogenin displayed potent levels of cytotoxic activity against the KB 3-1 cell line with an ED50 value of 0.8 nM. Upon initial isolation the relative and absolute stereochemical assignment of chamuvarinin (72) was unable to be readily achieved through ¹H and ¹³C NMR analysis. The initial synthetic route described herein has enabled the relative and absolute stereochemical determination of chamuvarinin (72) through the first total synthesis completed in 20 longest linear steps in 1.5% overall yield. A revised synthetic strategy towards chamuvarinin (72) was completed in 17 longest linear steps in 2.2% overall yield. The revised route facilitated the assembly of non-natural chamuvarinin-like analogues and their trypanocidal and cytotoxic activities have been assessed. The synthesis of these analogues has formed the basis of a more focussed study through the design and synthesis of simplified triazole (295), isoxazole (325) and butenolide triazole (305) analogues as potential Trypanosoma brucei (causative agent in African Sleeping sickness) inhibitors.
47
Fouche, Marianne. "Total synthesis of cruentaren A." Thesis, Imperial College London, 2012. http://hdl.handle.net/10044/1/14610.
Full textAbstract:
Cruentaren A, a highly cytotoxic metabolite, which also inhibits F-ATPase, was synthesized using our recently developed methodology on resorcylic acid lactones natural products. [Molecular structure diagrams appear here. To view, please open pdf attachment] Alcohol A was prepared on a multigram scale in 13 steps starting from (S)-Roche ester and using highly stereoselective reactions such as Evans aldol reaction and asymmetric propargylation. [Molecular structure diagrams appear here. To view, please open pdf attachment] Key fragment B was synthesized in 11 steps from 1,3-propanediol. The 1,2-anti-configuration was installed with a Brown crotylation. Diketo-dioxinone D was generated from C-acylation between Weinreb amide B and keto-dioxinone C. Ketene generation by thermolysis followed by trapping with alcohol A and aromatization afforded resorcylate derivative E. [Molecular structure diagrams appear here. To view, please open pdf attachment] Finally after a sequence consisting of the following key steps: ring closing alkyne metathesis, coupling between amine G and acid H and Lindlar hydrogenation, cruentaren A was obtained.
48
Salehi-Rad, Ramin. "Total synthesis of auripyrone A." Diss., Restricted to subscribing institutions, 2009. http://proquest.umi.com/pqdweb?did=1973896461&sid=1&Fmt=2&clientId=1564&RQT=309&VName=PQD.
Full text
49
Goh, Simin Shermin. "Total synthesis of rubriflordilactone A." Thesis, University of Oxford, 2015. https://ora.ox.ac.uk/objects/uuid:796adfdf-b4d5-474d-85a6-d2e19c1085db.
Full textAbstract:
Rubriflordilactones A and B are highly oxygenated nortriterpenoid natural products isolated from Schisandra rubriflora. The latter is of particular biological interest as it shows significant anti-HIV activity. Two transition metal-catalysed cascade cyclisation approaches for the formation of the CDE rings of the rubriflordilactones were developed. Palladium-catalysed cyclisation of bromoenediynes and cobalt-catalysed triyne cyclotrimerisation both transform acyclic precursors into 7,6,5-bisannelated arenes in a single step. Two enantioselective syntheses of the AB ring fragment common to both rubriflordilactones, with bromoene or alkyne functional groups required for the respective cyclisation methods, are described; along with the refinement of a route to the CDE diyne fragment of rubriflordilactone A. From these fully functionalised bromoenediyne and triyne substrates, both metal-catalysed cyclisation methods were successful; these strategies converged on a late-stage intermediate bearing the ABCDE ring system of rubriflordilactone A. Construction of the F ring, followed by attachment of the G ring by an intriguing oxo-carbenium ion addition reaction completed two enantioselective total syntheses of (+)-rubriflordilactone A.
50
Wada, Hiroki. "Total synthesis of plantazolicin A." Thesis, University of Nottingham, 2017. http://eprints.nottingham.ac.uk/37595/.
Full textAbstract:
Chapter 1 is an introduction of this thesis highlighting the importance of natural products in drug discovery utilising chemical modification of the original motif, especially together with an application of various bioisosteric approaches. Then, it gives an overview of a natural product, plantazolicin A which contains multiazoles with peptide bioisosteric properties. Other azole containing natural products including Thiazole/Oxazole Modified Microcins (TOMMs) are also introduced here. The current practical synthetic methods of the azoles such as thiazole and oxazole are discussed, especially with newly developed rhodium(II)-catalysed oxazole formation reaction via rhodium carbenoids derived from -diazocarbonyl compounds. Chapter 2 describes the total synthesis of plantazolicin A with the retrosynthetic plan by using the carbene chemistry, mainly starting from two precursors to prepare the key intermediate I and II. Each synthetic method is detailed including the choice of the optimum protecting groups and their development. The multi-oxazoles are formed via rhodium(II)-catalysed oxazole formation reactions with -diazocarbonyl compounds and the detailed procedures are explained. The two key intermediates I and II are combined together to give the main plantazolicin A scaffold and the detailed investigation to remove the protecting groups are also discussed here. A conformational study was carried out with extensive NMR nOe study together with molecular modelling to find the most stable conformational energy. A hairpin-like 3D structure of plantazolicin A is revealed here. In Chapter 3, the design of analogues of plantazolicin A is discussed and the synthesis is detailed using rhodium(II) catalysed oxazole formation reaction, following the success of the total synthesis of plantazolicin A. The analogues are tested against the growth of bacteria, especially methicillin-resistant Straphylococcus aureus (MRSA). The detailed structure-activity relationship (SAR) is also discussed here. Chapter 4 summarises the results of chapter 2 and 3, and chapter 5 contains full experimental details for all the work carried out.