Abstract not available

Abstract not available

Abstract not available

Abstract not available

Includes bibliographical references. / This project was initiated by the observation that a natural glyeoside of a triterpene, which incorporated the allylic alcoholic moiety 1 gave the novel ketone diene 2 when it was subjected to acetolysis. A number of octahydronaphthalinols (1, R=H) Δ 1 ( 9) octalinols), ' were prepared by reduction of the α, β unsaturated octalones obtained from cyclohexanones condensed with α, β -unsaturated ketones. These octalinols were characterised as their acetates (1, R=Ac). The attempts to convert these to the desired ketone dienes 2 by reaction with mixtures of acetic anhydride-acetic acid-boron trifluoride proved unsuccessful. Two model compounds derived from hecogenin and incorporating the octalinol residue 1 were also prepared in the hope that the analogous ketone 2 might be obtained. This reaction, too, was unsuccessful.

3,5-Dimethylorsellinic acid (DMOA)-derived meroterpenoids are a rich, structurally diverse family of natural products with a range of biological activities. Several total syntheses have been completed to date, but no broad synthetic scheme has been developed. In order to address this problem, a synthetic platform to produce 3,5-dimethylorsellinic acid (DMOA) meroterpenoids has been developed. Using a biomimetic strategy, DMOA was directly coupled to farnesyl electrophiles using a regioselective, base-mediated alkylative dearomatization strategy. Further chemical reactions including methylation and polyene cyclization resulted in the production of five unique tetracyclic DMOA-derived meroterpenoids. An understanding of the stereochemical outcome was explained via computational and experimental methods. Further development of the platform involved incubation of synthetic farnesyl-DMOA coupling substrates with terpene cyclase enzymes in a collaborative effort to produce novel chemoenzymatic DMOA-derived meroterpenoids. DMOA and DMOA methyl ester were employed in this strategy with multiple farnesyl derivatives to create both natural and non-natural DMOA-derived products. After both chemical and chemoenzymatic studies were completed, additional studies were initiated to synthesize the specific meroterpenoid target asperterpene A, an inhibitor of the B-secretase (BACE1) enzyme. A strategy involving direct alkylation of the decalin core using DMOA will be described, as well as a synthetic strategy from (-)-carvone. / 2023-09-10T00:00:00Z

Bibliography: pages 380-395. / A series of phosphate esters containing the E.-nitrophenyl moiety as a leaving group were synthesised and their base catalysed hydrolysis and electron impact-induced fragmentations studied. Heterocyclic ester substituents were present in some of the substrates and in-this sense they were considered as models for a nucleotide molecule containing both the 11 energy-rich11 phosphate bond and the nitrogen heterocyclic ring. The relative reactivity of the phosphorus-E,-nitrophenoxide bond was taken as a probe for nitrogen (pyridyl or quinolyl) participation in the substitution reaction. Although the heterocyclic derivatives show that the introduction of the nitrogen centre increases the rate of base catalysed hydrolysis, the reactivity enhancement is. not significant and results probably from polar effects rather than from intra-molecular catalysis. A comparison of the mass spectra of the heterocyclic and carbocyclic analogues, reveal differences which are significant (in the pyridyl substrates) and dramatic (in the quinolyl substrate) with regard to the fragmentation involving the E.-nitrophenoxy radical expulsion and formation of the corresponding phosphorylium ion. Synthetic approaches towards dimethylaryl and dimethyl(arylalkyl) phosphates are discussed. Nucleophilic displacement at the methyl ester carbon, and in particular the oxygen+ nitrogen methyl group transfer in these substrates occurs readily, complicating the synthetic procedures and lowering the stability of products. Dimethyl-(2-pyridylmethyl) phosphate isomerises in water to the zwitterionic N-methylpyridinium derivative via bimolecular methylation. The kinetics of the reaction were studied and no evidence for intra-molecular methyl transfer was obtained. - ii - The isomerisation of dimethyl-(quinolin-8-yl) phosphate in water also provides evidence for the bimolecular methylation. The crystal and molecular structure of dimethyl-(quinolin-8-yl) phosphate was determined and has revealed that the orientation of the CH 3 groups in the crystal provide no indication for the occurrence of methyl transfer in the solid state. The dynamics of the prepared phosphate derivatives studied in solutions were also investigated by means of mass spectrometry. Fragmentation patterns and their relative contributions are presented and discussed. The effect of solvent on the rates of the reaction between trimethyl phosphate and i) pyridine and ii) 4-(dimethylamino)pyridine, was studied at 25 - 65°C using NMR techniques. The solvents used were DzO, CD30D, CD3CN and DzO/CD30D and DzO/CD3CN mixtures. Water (DzO) is the most effective medium for the methyl transfer reaction. We attribute this to the strong hydrogen bonding between water and the departing dimethyl phosphate anion in the transition state. Activation parameters obtained for the reactions in pure solvents confirmed our interpretation of the hydrogen bonding effect operating in the transition state. Fragmentation of S-arylethyl phosphates has been investigated. A novel feature is exhibited by S-arylethyl phosphorochloridates. They easily decompose thermally yielding 1-chloro-2-arylethanes and/or arylethylenes presumably via concerted C-O and P-Cl bond fission involving a phenonium ion intermediate and expulsion of a metaphosphate species.

Includes bibliographical references. / As indicated by the title, this dissertation deals with the investigation of the syntheses of a number of novel quinones. Chapter I deals with the syntheses of quinonoid derivatives of the compounds isobenzofuran and isoindole. These are the parent species of that series of heterocyclic compounds which contain a single heteroatom and are isoelectronic with naphthalene. They have been of considerable interest to workers in recent years, but have proved to be relatively unstable. We have therefore set out to prepare stable quinonoid derivatives of these. In Chapter II we have sought to develop, via regiospecific Diels-Alder additions, simple syntheses of some synthetically useful napthaquinonoid systems. The formation of many of these, required in the past as intermediates for the syntheses of a number of naturally occurring quinones, has previously proved tedious. Tae study of these addition reactions has afforded a direct route for the synthesis of the natural quinone, droserone. Finally, in Chapter III, some of the napthaquinones produced in Chapter II have been employed as intermediates in the syntheses of certain naturally occurring quinonoid species. These include a caryopterone and model compounds for the proposed syntheses of the anti biotics, Juglomycins A and B.

Includes bibliographical references. / The first part of this thesis deals with the attempts made to synthesise 4 - hydroxypiloquinone. The proposed synthesis involved the making of two correctly substituted aromatic moieties that could be joined together to give a stilbene, which on irradiation would give a phenanthrene, that could be further elaborated to give a suitable precursor to 4 - hydroxypiloquinone. All attempts to convert the precursor to the required quinone were unsuccessful. In the second part of this thesis, a number of 2 - acetyl - 3 -alkylamino - 6 - anilino - 1,4 - benzoquinones were prepared by the reaction of 2 - acetyl - 3,6 - dianilino - 1,4 - benzoquinone with alkylamines in chloroform. Irradiation of these alkylamino - p -benzoquinones with ultra-violet light gave benzoxazoles where an á -hydrogen atom was present in the alkylamino substituent, except for the cyclohexylamino - and s - butylamino - benzoquinones which gave an unstable photo-product. With t - butylamino - benzoquinone no photoreaction was observed.

Bibliography: pages 248-257. / The naphtho[2,3-c]pyran ring system occurs not infrequently in Nature as derivatives of the 5,10-quinone. Examples include the eleutherins, the nanaomycins and the protoaphins some of which have been shown to possess antibiotic activity. The synthesis of these natural products requires appropriate regiospecific aromatic oxygenation of 2- acetylnaphthoquinone. Syntheses of 3-acetyl-5-methoxy-1, 4- naphthoquinone and the corresponding 5,7-dimethoxy analogue are described and the use of these in the syntheses of several naturally occurring pyranquinones or their derivatives, has been investigated. In the course of this work, an unusual Fries rearrangement and a novel baseinduced cyclisation were discovered - the latter affording several naphtho[2,3-c]pyrans in high yield. Previous routes to (±)-isoeleutherin and (±)-deoxyquinone A dimethyl ether have been recorded, but they give rise to a mixture of eleutherin and isoeleutherin in the first case, and a mixture of deoxyquinone A dimethyl ether and its cisdimethyl isomer. The synthetic routes to isoeleutherin and deoxyquinone A dimethyl ether developed during this investigation are highly stereoselective. The formation of the dimethyl ethers of quinones A and A', which is also highly stereoselective represents the first reported synthesis of the degradation products of the aphid pigments, protoaphin-fb and protoaphin-s1. The synthesis of 7-methoxyeleutherin is also described. The reaction of trifluoroacetic anhydride with various naphthalene derivatives is described and the potential of some of these acylated naphthalenes to be employed in the syntheses of naphtho[2, 3-c]pyrans and naturally occurring quinones has been investigated.