Doctoral Degrees (Chemistry)

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Browsing Doctoral Degrees (Chemistry) by Subject "Absolute configuration"

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    The constitution of oligomeric benzofuranoids
    (University of the Free State, 1999-05) Bekker, Riaan; Brandt, E. V.; Ferreira, D.
    English: Berchemia zeyheri is known for its unique red heartwood, a property that was probably responsible for the first phytochemical investigation into the flavonoid content of this tree. The heartwood contains a unique series of biflavonoids with one of more benzofuranoid moieties. These are usually found in diastereomeric mixtures, the biogenetic origin and stereochemistry of which have hitherto been unknown. This investigation thus represents a renewed effort to solve some of the intricate problems associated with these compounds. The high concentration of maesopsin in the heartwood made extensive enrichment and fractionation by the use of Craig countercurrent distribution techniques and Sephadex LH- 20 gelchromatography necessary. The two diastereomers of 4',5, 7-tri-O-methylnaringenin-(3a~ 7)-2,4,4',6-tetra-Omethylmaesopsin were, for the first time, successfully isolated and separated. Reduction of these diastereomers with Na(CN)BH3 gave two enantiomeric pure fragments. The conformations of the heterocyclic rings of these fragments were established by molecular mechanics (MMX and GMMX) and semi-empirical methods (AMI). These results allowed the absolute configuration of the fragments to be deduced from CD-curves of the compounds by application of Snatzke's rule for a,~-unsaturated five-membered cyclic rings. A n.O.e. correlation observed for one of the diastereomers only, correlates the stereocenter of the maesopsin moiety, of known absolute configuration, with a specific configuration of the naringenin unit, thus defining the absolute configuration of the dimer. These results also allowed the determination of the absolute stereochemistry of two regioisomers of the above dimers, 4',5, 7-tri-O-methylnaringenin-(3a~5)-2,4,4',6-tetra-Omethylmaesopsin and its epimer. The 13CNMR spectra of these related dimers were also studied and fully elucidated by means of HMQC and HMBC experiments. The structure and stereochemistry of two novel isoflavanone-benzofuranone biflavonoids, 4',5,7-tri-Omethyldihydrogenistein-fêcc-» 7)-2,4,4',6-tetra-O-methylmaesopsin and its epirner, were similarly determined. Resolution of maesopsin, the main metabolite in the heartwood, by means of HPLC using a chiral column, for the first time gave access to the two enantiomers of this benzofuranoid. 4,4',6- Tri-O-methyl-2-deoxymaesopsin-(2~ 7)-2,4,4',6-tetra-O-methyl-maesopsin and its epimer, consist of two benzofuranoid constituent units. An X-ray crystal structure was obtained for the one diastereomer, but due to the presence of a symmetric Pbea point group, only the relative configuration could be determined. After the racemic nature of each of the diastereomers was determined, each epimer was resolved with HPLC into its constituent enantiomers. The information obtained from the CD curves and crystal structure allowed the determination of the absolute stereochemistry of each of the enantiomers. Four further epimeric biflavonoids were isolated as the hepta-O-methyl ethers. Evidence obtained from 13C NMR data suggested the presence of a y-lactone functionality in the upper benzofuranoid moiety, identifying the dimers as the epimers of 4,6-dimethoxy-3-( 4- methoxy-benzyl)benzo[b ]furan-2(3H)-one-(2~5)-2,4,4',6-tetra-O-methylmaesopsin and the (2~ 7)-coupled regio-isomer. In order to supplement the above data, an asymmetric synthesis of maesopsin was attempted. The first attempt involved the oxidation of 2-( 4-methoxybenzyl)-4,6- dimethoxybenzo[b ]furan-3(2H)-one, obtained by reduction of the corresponding aurone, with AD-mix-a, a stereoselective catalyst, or chiral oxaziridine. The former afforded the desired product in low yield but no stereo selectivity while the latter method realized a much-improved yield, but still with no selectivity. This lack of selectivity is attributed to equilibrium of the product with the a-diketone. Attempts to prevent the formation of this equilibrium product were unsuccessful. A second synthetic attempt involved benzylation of 2,4,6-trimethoxybenzo[b]furan-3-(2H)-one with (-)-sparteine as chiral auxiliary, but again resulted in high yields but no stereo selectivity.