The constitution of oligomeric benzofuranoids
| dc.contributor.advisor | Brandt, E. V. | |
| dc.contributor.advisor | Ferreira, D. | |
| dc.contributor.author | Bekker, Riaan | |
| dc.date.accessioned | 2017-10-18T09:29:04Z | |
| dc.date.available | 2017-10-18T09:29:04Z | |
| dc.date.issued | 1999-05 | |
| dc.description.abstract | 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. | en_ZA |
| dc.description.abstract | Afrikaans: Berchemia zeyheri is bekend vir 'n unieke rooi kernhout, 'n eienskap wat aanvanklik verantwoordelik was vir die eerste fitochemiese ondersoek op hierdie houtsoort. Die kernhout bevat o.a. 'n unieke reeks biflavonoïede met een of meer bensofuranoïedeenhede wat kenmerkend as diastereomeriese mengsels aangetref word. Die oorsprong van die diastereomeriese aard van hierdie mengsels, asook die stereochemie van die verbindings, kon tot op hede egter nog nie bepaal word nie. Na aanleiding hiervan is 'n herondersoek na die flavonoïedinhoud van Berchemia zeyheri aangepak. Die hoë konsentrasie maesopsin in die kernhout het uitgebreide verryking en fraksionering deur benutting van o.a. Craig teenstroomverdelingstegnieke en Sephadex LH-20 jelchromatografie genoodsaak. Die twee diastereomere van 41,5,7-tri-O-metielnaringenin-(3a~7)-2,4,4',6-tetra-Ometielmaesopsin is vir die eerste keer suksesvol geïsoleer en geskei. Reduksie van hierdie diastereomere met Na(CN)BH3 gee aanleiding tot twee suiwer enantiomeriese brokstukke. Die konformasie van die heterosikliese ring van hierdie brokstukke is m.b.v. molekulêre meganika (MMX en GMMX) en semi-empiriese metodes (AMI) bepaal. Na aanleiding van hierdie resultate kon die absolute konfigurasie van die fragmente m.b.v. van Snatzke se reël vir a,p-onversadigde vyfledige sikliese ketone vir die eerste keer uit die SD-kurwes bepaal word. 'n N.O.e. korrelasie wat slegs byeen diastereomeer waargeneem is, korreleer die stereosentrum van die maesopsineenheid met 'n bepaalde konfigurasie van die naringenineenheid en gee toegang tot die absolute konfigurasie van die dimere. Hierdie resultate laat ook die bepaling van die absolute stereochemie van 4',5,7-tri-Ometielnaringenin-( 3a~5)-2,4,4',6-tetra-O-metielmaesopsin en sy epimeer, twee regioisomere van die bogenoemde dimere, toe. Die 13CKMR spektra van hierdie dimere is ook bestudeer m.b.v. HMQC en HMBC eksperimente. Die stuktuur en stereochemie van twee unieke isoflavanoon-bensofuranoon biflavonoïede, 4',5,7-tri-O-metieldihydrogenistein- (2a~ 7)-2,4,4',6-tetra-O-metielmaesopsin en sy epimeer, is ook bepaal. Resolusie van maesopsin, die hoof metaboliet in die kernhout, deur middel van HPLC met 'n chirale kolom gee vir die eerste keer toegang tot die twee enantiomere van hierdie benzofuranoïed. 4,4',6- Tri-O-metiel-2-deoxymaesopsin-(2~ 7)-2,4,4',6-tetra-O-metiel-maesopsin en sy epimeer bestaan uit twee bensofuranoïedeenhede. Ten spyte van die feit dat 'n X-straal kristalstruktuur van die een diastereorneer verkry is, kon slegs die relatiewe konfigurasie van hierdie verbinding bepaal word aangesien die Pbca ruimtegroep waarin die kristalle gekristalliseer het, inherent simmetries is. Nadat vasgestel is dat elk van die epimere rasemies is, is hulle m.b.v. HPLC geskei om vier enantiomere te gee. Die inligting verkry vanaf die SD-kurwes en kristalstruktuur het die bepaling van die absolute konfigurasie van elk van die enantiomere moontlik gemaak. Vier verdere epimeriese dimere is ook as die hepta-O-metiel eters geïsoleer. Inligting vanaf die l3C KMR data van hierdie verbindings dui op die teenwoordigheid van 'n ylaktoon funksionaliteit in die boonste bensofuranoïedeenheid. Die dimere is geïdentifiseer as die epimere van 4,6-dimetoksi-3-( 4-metoksibensiel)benso[b ]furan-2(3H)-00n-(2~5)- 2,4,4',6-tetra-O-metielmaesopsin en die (2~ 7) gekoppelde regio-isomere. Ten einde die bogenoemde inligting aan te vul, is 'n asimmetriese sintese van maesopsin aangepak. Die eerste poging behels die oksidasie van 2-(4-metoksibensiel)-4,6- dimetoksibenso[b]furan-3(2H)-00n, wat verkry is deur die reduksie van die geskikte auroon, deur gebruik te maak van AD-mengsel-a, 'n stereoselektiewe katalis, en chirale oksaziridien. Die eerste van hierdie metodes het die vereiste produk in lae opbrengs verskaf, maar sonder enige stereoselektiwiteit terwyl die tweede metode die produk in hoë opbrengs gee, maar weereens sonder selektiwiteit. Hierdie gebrek aan seleksie kan waarskynlik toegeskryf word aan die ewewig wat tussen die produk en die a-diketoon bestaan. Pogings om die vorming van die a-diketoon te beperk was onsuksesvol. 'n Tweede poging behels die bensilering van 2,4,6-trimetoksibenso[b ]furan-3(2H)-oon met (-)-sparteine as chirale hulpmiddel. Weereens is maesopsin in hoë opbrengs gevorm, maar sonder enige stereoselektiwiteit. | af |
| dc.identifier.uri | http://hdl.handle.net/11660/7301 | |
| dc.language.iso | en | en_ZA |
| dc.publisher | University of the Free State | en_ZA |
| dc.rights.holder | University of the Free State | en_ZA |
| dc.subject | Berchemia zeyheri | en_ZA |
| dc.subject | Diastereomeric, | en_ZA |
| dc.subject | Benzofuranone biflavonoids | en_ZA |
| dc.subject | Absolute configuration | en_ZA |
| dc.subject | Asymmetric synthesis of benzofuranoids | en_ZA |
| dc.subject | Flavonoids | en_ZA |
| dc.subject | Botanical chemistry | en_ZA |
| dc.subject | Thesis (Ph.D. (Chemistry))--University of the Free State, 1999 | en_ZA |
| dc.title | The constitution of oligomeric benzofuranoids | en_ZA |
| dc.type | Thesis | en_ZA |