Thesis (Ph. D.)--University of Wisconsin--Madison, 1948. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Chapter I describes the synthesis of a trishomocubyl helical tubuland diol and some aspects of its inclusion chemistry. Thus, all three isomers of 4,7-dimethylpentacyclo[6.3.0.0^2,6.0^3,10.0^5,9]undecane-4,7-diol have been prepared and their X-ray structures have been determined. The syn,syn-isomer crystallizes in a double-stranded hydrogen-bonded lattice, while anti,syn-isomer forms a hydrogen-bonded layer lattice. In contrast, the anti,anti-isomer is a new member of the helical tubuland diol host family; its crystal lattice consists of parallel canals with a trefoil-shaped cross-section of area 25.4 Å^2. Chapter II describes the synthesis of new molecular clefts. These molecular clefts have been synthesized via base-promoted reactions of 3,6-diaryl-l,2,4,5-tetrazines with tetracyclo[6.3.0.0^4,11.0^5,9]undecane-3,6-dione and with tricyclo[6.3.0.0^2,6]undecane-3,11-dione, respectively. Compounds of this type are of interest as a potential new class of host molecules for use in host-guest complexation studies. Chapter III reports the synthesis of stereospecifically deuterated spiro(oxetane-3,8'-pentacyclo[5.4.0.0^2,6.0^3,10.0^5,9]undecanes) and their acid-promoted ring opening and concomitant rearrangements. The deuterium-containing reaction products have been characterized via analysis of their NMR and mass spectra. The results strongly suggest that intramolecular 1,5-hydride shifts provide an important pathway through which the acid promoted rearrangements occur. Chapter IV reports the oxidation of heptacyclo-[6.6.0.0^2,6.0^3,13.0^4,11.0^5,9.0^10,14] tetradecane (HCTD) via application of Barton's "GoAgg" systems. The products have been characterized by NMR and mass spectral analysis. Under GoAgg^v conditions, oxidation of HCTD proceeds to afford heptacyclo [6.6.0.0^2,6.0^3,13.0^4,11.0^5,9.0^10,14]tetradecan-7-one in 1% yield.

Graduation date: 2001

Thesis (Ph. D.)--University of Wisconsin, 1967. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliography.

No description available.

The objective of this study was to synthesize new energetic, strained, saturated polycyclic compounds. For this purpose, new methodology has been developed, as follows: (i) Ketenes have been generated in situ via treatment of aldo-, keto- or alkenoic acid with either toluenesulfonyl chloride or 2-chloro-1-methylpyridfniurn iodide (Mulkaiyama's reagent). The reactive intermediates thereby generated have been found to undergo intramolecular [2+2] cycloaddition reactions in these systems.

Computational studies have shown that cage skeletons (7) have the tendency to impose a 310-helix as well as an áL-helix on the polypepeptide chain. Residues such as 7 are the useful tools for study of the conformational preferences of peptide models, the design of peptide analogues with improved pharmacokinetics profiles and the development of pharmacophore models. Synthesis of pentacycloundecane amino acid analogue suitable for peptide synthesis would enable us to verify the computational predictions and to contribute to this very active field of research. The sterically hindered 8-amino-pentacyclo[5.4.0.02,6.03,10.05,9]undecane-8-carboxylic acid (7) was synthesised by hydrolysis of the novel bis-Boc protected pentacycloundecane-hydantoin (30). Progress to incorporate 7 into a non-natural peptides is reported. A computational investigation on the regioselective acetylation of hydantoin derivatives which includes PCU hydantoin, 5.5-dimethylhydantoin and 5-methylhydantoin is also reported. The results of the computational investigation initiated the regioselective synthesis of the mono-Boc and bis-Boc derivatives of 5,5-dimethylhydantoin and 5-methylhydantoin. These compounds have not been reported before. / Thesis (M.Sc.)-University of KwaZulu-Natal, 2005.

I. Diels-Alder reactions of 1,2,3,4,9,9-hexachloro-1,4,4a,8a-tetrahydro-1,4-metha- nonaphthalene (16) and 1,2,3,4,9,9-hexachloro-1,4,6,7-tetrahydro-1,4-methanonaphthalene (17) toward dienophiles N-methyl-1,2,4-triazoline-3,5-dione (MTAD), N-phenyl-1,2,4-triazoline-3,5-dione (PTAD) and/or N-methylmaleimide (NMM) have been examined. II. Epoxides derived from functionalized 1,4,4a,9a-tetrahydro-9,10-dioxo-1,4-methanoanthracenes (1a and 1b) undergo acid- and base-promoted intramolecular nucleophilic ring-opening to form new polycyclic alcohols. III. The title cycloalkylidenecarbene has been generated via reaction of 8-methylenepentacyclo[5.4.0.0^{2,6}.0^{3,10}. 0^{5.9}]undecan-11-one (44) with diethyl diazomethyl-phosphonate (DAMP). This species could be trapped in situ by cyclohexene, thereby affording the corresponding cycloadduct 46a and 46b.

A variety of novel cage-functionalized pyridyl containing crown ethers have been prepared for use in selective alkali metal complexation studies. A highly preorganized, cage-functionalized cryptand also has been designed and has been synthesized for use as a selective Li+ complexant. The alkali metal picrate extraction profiles of these cage-functionalized crown ethers also have been studied. Novel cage-functionalized diazacrown ethers have been prepared for selective alkali metal complexation studies. Alkali metal picrate extraction experiments have been performed by using this new class of synthetic ionophores to investigate the effects of cage-annulation and the influence of N-pivot lariat sidearms upon their resulting complexation properties. Novel pyridyl containing calix[4]arene receptors were prepared. Analysis of their respective 1H NMR and 13C NMR spectra suggests that calix[4]arene moieties in the ligand occupy the cone conformation. The complexation properties of these host molecules were estimated by performing a series of alkali metal picrate extraction experiments. An optically active cage-functionalized crown ether which contains a binaphthyl moiety as the chiral unit was prepared. The ability of the resulting optically active crown ether to distinguish between enantiomers of guest ammonium ions (i.e., phenylethylamonium and phenylglycinate salts) in transport experiments was investigated. Hexacyclo[11.2.1.02,12.05,10.05,15.010,14]hexadeca-6,8-diene-4,11-dione was prepared from hexacyclo[7.4.2.01,9.03,7.04,14.06,15] pentadeca-10,12-diene-2,8-dione. Unanticipated but remarkable acid and base promoted rearrangements of this new cage dione to novel polycyclic systems were observed and subsequently were investigated. The structures of the new systems thereby obtained were determined unequivocally by application of X-ray crystallographic methods. It is noteworthy that the reactions reported herein each provide the corresponding rearranged product in high yield in a single synthetic step. Pi-facial and regioselectivity in the thermal Diels-Alder cycloaddition between hexacyclo[11.2.1.02,12.05,10.05,15.010,14]hexadeca-6,8-diene- 4,11-dione and ethyl propiolate have been explored. This reaction proceeds via stereospecific approach of the dienophile toward the syn face of the diene p -system. However, [4+2]cycloaddition proceeds with only modest proximal/distal regioselectivity. The structure of the minor reaction product was established unequivocally via application of X-ray crystallographic techniques.

Despite over 50 centuries of living with the disease, tuberculosis (TB) still remains one of the oldest and deadliest diseases known to man and is gradually becoming a serious threat to the human race. According to the 2009 Global tuberculosis control report of the World Health Organisation (WHO), it is estimated that about 9.4 million incident cases of TB occurred globally. Of these cases an estimated 1.4 million were HIV positive of which 78 % were in the African region while 13 % are located in the South-East Asia Region. An estimate of 1.3 million deaths was reportedly caused by TB among HIV negative people. South Africa has the highest percentage of HIV patients living with tuberculosis. The design, synthesis and evaluation of novel polycyclic ‘cage’ amines for their pharmaceutical profiles are presented in this thesis. In this project a total of 12 novel intermediates and 31 novel products were synthesised. A thorough NMR elucidation of the various structures was also pursued. This study was motivated by the reported discovery of SQ109 by Sequella. SQ109 (N-Geranyl- N’-(2-adamantyl)ethane-1,2-diamine) shares the same 1,2 ethylenediamine pharmacophore with ethambutol (EMB), a commercial TB-drug. SQ109 also possess remarkable activity against MDR-TB which includes the EMB resistant strain suggesting that SQ109 is a new anti-TB drug and not an EMB analogue. SQ109 comprises of a polycyclic adamantane moiety, an isoprenyl moiety and a diamine. This study had three main aims, namely (a) the design and synthesis of novel polycyclic ‘cage’ amines derivatives; the polycyclic ‘cage’ moieties investigated in this study includes adamantane, trishomocubane, oxa-pentacycloundecane, aza-pentacycloundecane, pentacyclodecane and pentacycloundecane, (b) structural elucidation (using 2D NMR techniques) of synthesized novel polycyclic ‘cage’ amine derivatives (c) the anti-mycobacterial screening of novel polycyclic ‘cage’ amines derivatives against H37Rv, MDR (multi-drug resistant) and XDR (extensively-drug resistant) strains of Mycobacteria tuberculosis and (d) the anti-bacterial and anti-fungal screening of selected novel polycyclic ‘cage’ amine derivatives. Furthermore, the design, synthesis and NMR elucidation of a family of similar novel PCU diamine ligands are also reported herein. The aim of these ligands is to complex and transport copper ions to the sites of inflammation caused by arthritus. The known pharmaceutical properties of polycyclic ‘cage’ compounds such as their ability to cross membranes due to improved drug lipophilicity makes them suitable candidates for such a study. This project stems from a logic collaboration between UKZN, UCT (University of Cape Town) and CPUT (Cape Peninsula University of Technology) to test some of these cage diamines for activity against arthritus. Experimental work in this aspect is performed by the group of Prof. Graham E. Jackson (UCT) and Dr. Sebusi Odisitse (UPUT). / Thesis (Ph.D.)-University of KwaZulu-Natal, Westville, 2010.