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1	Model studies of carbocycle formation directed towards the synthesis of cytochalasin D Arnost, Michael Jay. January 1979 (has links) Thesis--University of Wisconsin--Madison. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references. Cytochalasins.
2	Synthesis of the cytochalasin D skeleton Reid, John Gregory. January 1983 (has links) Thesis (Ph. D.)--University of Wisconsin--Madison, 1983. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references. Cytochalasins.
3	Towards the synthesis of cytochalasin B Ramaswamy, Sowmianarayanan January 1982 (has links) Chapter I of this thesis deals with the syntheses of the key fragments for use in a proposed synthesis of cytochalasins A, B and F. The chiral precursor 86 of the macrocyclic fragment of the target molecules was prepared in good overall yield from (+)-citronellol using a new reagent which was developed for this purpose. Dienes 87, 88 and 89 were prepared from (E)-2-methyl-2-butenal following literature procedures. The chiral dienophile 124 which was required for an intermolecular Diels-Alder reaction was prepared in good overall yield from L-phenylalanine. A model Diels-Alder reaction between (E,E)-2,4-hexadiene and 124 provided a quantitative yield of the Diels-Alder adduct 126. However, Diels-Alder reactions between 87-89 and 124 were unsuccessful. Substrates 39-41 required for a proposed intramolecular Diels-Alder reaction were prepared. Attempted intramolecular reactions of 39-41 were unsuccessful. [Figure 1] The development and synthetic applications of two ethanedial (glyoxal)-based reagents are discussed in Chapter II. Chapter II-A deals with the preparation and alkylation studies of enamines of 2,2-bis(ethylthio)ethanal (162). This compound was prepared in good yield from ethanedial. Alkylation of the potassium salts of various enamines of 162 followed by in situ hydrolysis provided high yields of the alkylation products. This new reagent was used in the synthesis of compound 86, mentioned above, as well as the physiologically active diolides pyrenophorin and norpyrenophorin. Chapter II-B deals with the preparation and alkylation of 2,2-bis(ethyl-thio)acetonitrile (211). This compound was prepared in high yield from 162. Alkylation of the potassium salt of 211 with various electrophiles and conjugate addition with cyclic a,6-unsaturated ketones provided high yields of the alkylation products. The potential 1- and 2- carbon chain extension capability of this reagent has been demonstrated. [Figure 2] In Chapter III of this thesis a mechanistic investigation of a thermal [l,3]-alkyl shift in compounds 174 and 246-252 is described. An intermolecular, free-radical pathway for the migration was proposed on the [Figure 3] basis of the results of a crossover experiment, a significant positive entropy of activation combined with the lack of a solvent effect. An electron spin resonance signal observed during the rearrangement of 174 was consistent with the proposed radical pathway. / Science, Faculty of / Chemistry, Department of / Graduate Cytochalasins
4	An approach to the synthesis of the cytochalasans Harkin, Shaun Anthony January 1983 (has links) The cytochalasans, a group of biologically active secondary metabolites isolated from micro-organisms, are tricyclic compounds which comprise of a heavily oxygenated 11-, 13- or 14-membered ring trans -fused to a substituted 8-azabicyclo [4.3.0]nonane ring system. One approach to the total synthesis of the cytochalasans involves the intramolecular Diels-Alder cyclization of a suitable 3-substituted- Δ<sup>3</sup> - pyrrolin-2-one. As preliminary work, a synthetic route to 5̱S-1-acyl-5- benzyl-3-butyl- Δ<sup>3</sup> -pyrrolin-2-ones was developed, starting from the known lactam, 5̱R-5-benzylpyrrolidin-2-one. However, although these dienophiles reacted stereospecifically with 2̱E,4̱E-hexadiene, the reaction conditions were harsh (200°, 30-50 h) and the sequence suffered from low overall yields. The doubly activated dienophile, 5̱S-1-benzoyl-5-benzyl-3-(1-oxopropyl)- Δ<sup>3</sup> -pyrrolin-2-one, on the other hand, was available via an expeditious route from the N -protected lactam, 5̱R-5-benzyl-1-(tert-butyldimethylsilyl)pyrrolidin- 2-one. Moreover, the dienophile reacted stereoselectively with 2̱E,4̱Ehexadiene under milder conditions (100°, 8 h) to give, after deprotection, 7-benzyl-2,5-dimethyl-1-(1-oxopropyl)-8-azabicyclo[ 4.3.0] non-3-en-9-one. The stereochemistry of the isoindolone adduct was shown to be the same as in naturally occurring cytochalasans. The overall yield from 5̱R-5-benzylpyrrolidin- 2-one after seven steps was 16%. In comparative studies, the doubly activated dienophile 1-benzenesulphonyl- 3-(1-oxopropyl)- Δ<sup>3</sup> -pyrrolin-2-one was prepared and its reactions with 2̱E,4̱E-hexadiene and cyclopentadiene were studied. Although the stereoselectivity was better than for the N-benzoylated pyrrolin-2-one, isolated yields of cycloadducts were inferior. Thus,as a model for ah approach to the [13]cytochalasans, the dienedienophile, 5̱S ,12̱E,14̱E-1-benzoyl-5-benzyl-3-(1-oxohexadeca-12,14-dienyl)- Δ<sup>3</sup> -pyrrolin-2-one, was prepared in 20% overall yield from 5̱R-5-benzylpyrrolidin- 2-one. Regio- and stereoselective cyclization was achieved under high pressure conditions (11-13 kbar) to give a tricyclic compound in 16-35% yield. The stereochemistry of the deprotected major adduct was shown to be that required for cytochalasan synthesis. Thus, the intramolecular Diels- Alder approach to cytochalasan synthesis using diene-lactams was validated. 547 Cytochalasins : Synthesis
5	Spreading capacity and cytochalasin-induced capping as probes for plasma membrane/cytoskeletal function in human T-lymphocytes Otteskog, Per. January 1982 (has links) Thesis (doctoral)--Karolinska Institutet, Stockholm, 1982. / Extra t.p. with thesis statement inserted. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.
6	Spreading capacity and cytochalasin-induced capping as probes for plasma membrane/cytoskeletal function in human T-lymphocytes Otteskog, Per. January 1982 (has links) Thesis (doctoral)--Karolinska Institutet, Stockholm, 1982. / Extra t.p. with thesis statement inserted. Includes bibliographical references.
7	Natural Product Drug Discovery against Tropical Diseases Ma, Wai Sheung 01 January 2011 (has links) This dissertation describes the isolation of secondary metabolites from natural origins through a series of chromatographic techniques and spectrometric characterization in the effort of drug discovery. The isolated compounds obtained were used as drug leads against tropical diseases, namely malaria and leishmaniasis. While first chapter offers an introduction on the use of a natural product by itself as an effective therapeutic and its role on inspiring the discovery of new drugs, the later chapters will concentrate on isolation and characterization of bioactive natural products from an Antarctic sponge and mangrove endophytic fungi during the dissertation work. The second chapter describes the attempt to develop a new method of solving the absolute configuration of tertiary alcohol using lanthanide chiral shift reagent and 13C NMR spectroscopy. The third chapter describes the isolation of five new steroids, norselic acids A-E, from Crella sp. collected in Antarctica. The structures of the norselic acids were established by NMR and MS techniques. The absolute stereochemistry of norselic acid A was elucidated by SXRD. The antimicrobial and anti-leishmania activities of norselic acid A have been studied. Norselic acid A displays antimicrobial activities against methicillin-resistant S. aureus (MRSA), S. aureus, E. faecium, and C. albicans. Norselic acids B-E exhibit mild antimicrobial activities. All norselic acids exhibit strong cytotoxicity against leishmania. The fourth and fifth chapters describe a Medicine for Malaria Venture (MMV) funded malaria bioassay-guided screening program. The chemical investigation of the crude endophytic fungal extracts has led to the isolations of a series of known cytochalasins along with the discovery of a few new compounds, including a new simple carboxylic acid, and several known and novel compounds belonging to the dimeric xanthone family. Majority of the cytochalasins display mild cytotoxicity and outstanding inhibition to chloroquine-resistant reference strain Plasmodium falciparum (W2) with IC50 ranging from 25.8 nM to 2900nM. However, their cytostatic properties hinder them from being a good drug candidate. The dicerandrols display good activity with the lowest IC50=0.63 μM against malaria with low cytotoxicity. The structures of the compounds isolated and the associated anti-malarial activities are reported herein. Chemical investigation Cytochalasins Dicerandrols Leishmania Malaria Norselic acids American Studies Arts and Humanities Chemistry
8	Structure Elucidation of Bioactive Compounds Isolated from Endophytes of Alstonia scholaris and Acmena graveolens Hundley, Nicholas James 02 September 2005 (has links) (PDF) Alstonia scholaris is an evergreen tree native to Southeast Asia and Australia. It is commonly used as a medicinal plant throughout these regions. In the present study, an endophyte of the genus Xylaria was isolated from a stem of Alstonia scholaris, its mycelia and exudate extracted, and the extract assayed for growth inhibition of HeLa cancer cells in vitro. Several known compounds were isolated and identified based on NMR, infrared, and mass spectral data. The compounds identified are 19,20-epoxycytochalasin C; 19,20epoxycytochalasin D; and xylobovide. Two other compounds, fusaric acid and dehydrofusaric acid, were discovered in an endophyte of the Hypocreales family inhabiting the plant Acmena Graveolens. endophtye endophytes endophytic (endophyt) fungi fungal symbiosis rDNA ribosomal DNA fungal taxonomy ITS cytochalasins cytochalasans xylobovide fusaric acid dehydrofusaric acid xylaria xylariaceae rosellinia necatrix taxol HPLC NMR GC gas chromatography MS mass spectrometry (mass spec) IR infrared spectroscopy PCR natural products ethnobotany ethnomedicine COSY HMQC HMBC Biochemistry Chemistry

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