Structure and synthesis of polyphenols from cyclopia subternata
| dc.contributor.advisor | Brandt, E. V. | |
| dc.contributor.advisor | Kamara, B. I. | |
| dc.contributor.author | Brand, D. J. | |
| dc.date.accessioned | 2017-04-25T09:49:55Z | |
| dc.date.available | 2017-04-25T09:49:55Z | |
| dc.date.issued | 2002-06 | |
| dc.description.abstract | English: Cyclopia subternata (Fabaceae), from which Honeybush tea is brewed, is one of approximately 24 Cyclopia species of woody legumes endemic to the Cape fynbos (Cape macchia) region of South Africa. Supported by results from our initial investigations on C. intermedia, demonstrating the presence of phenolic compounds including coumestans, isoflavones, flavanones, xanthones, a flavone, pinitol, p-coumaric acid and flavonoid glycosides, the tea is gaining popularity as a health beverage. Presence of these compounds that are claimed to have interesting pharmacological properties, supported by belief that the tea contains very little, if any, caffeine and low tannin content, as well as its usage as a medicinal plant by the people of the Western and Eastern Cape prompted investigations on the subternata species. The acetone and methanol extracts of the unfermented shoots and stems of C. subternata were subjected to chromatographic separations (Shephadex LH-20 column and preparative thin layer) which afforded a novel flavan, flavonols, flavanones, flavones, isoflavone and C6.C2- and C6.C1-type compounds. Their full acetate or methylated derivatives were elucidated and characterized by high resolution (300 MHz) ¹H NMR speetrometry which included COSY, NOESY, HMQC, HMBC, DEPT 135° experiments and ¹³C NMR spectroscopy, Molecular Modeling and Circular Dichroism. Along with (+)-Pinitol a novel apiofuranosyl (1"—›6')-glucopyranosyl carboxylic acid was isolated as a non-flavonoid compound. The flavonoid aglycones isolated included epicatechin-3-0-gallate (flavanol), luteolin (flavone) and orobol (isoflavone). The nonflavonoid glycosides included a 4-0-gl ucopyranosyl tyrosol, apiofuranosyl (l"—›6')- glucopyranosyl benzaldehyde and the acetate derivatives of two new O-glycosides namely 1-[(β-D-2',3' ,4' -tri-O-acetylglucopyranosyloxy ]-2-(3,5-diacetoxyphenyl)ethane and l-acetoxy-2-(β-D-2',3',4',6' -tetra-O-acetylglucopyranosyloxy)ethane. The flavonoid O-glycosides comprised a novel 3',4',7-trihydroxy-5-(glucopyranosyloxy) flavan, the flavone, scolymoside and the flavanones, hesperedin, narirutin and eriocitrin. C-glycosides isolated includes the xanthone, mangiferin, a C-6-glycosylated kaempferol as well as two new C-glycosides, 3,4' ,6, 7-tetrahydroxy-5-W-D-glucopyranosyl) flavonol and 3' ,4',5,5', 7-pentahydroxy-8-(β-D-glucopyranosyl) flavanone. Due to the novelty and the many proposed health properties of flavans, the relatively unexplored routes to flavonoid O-glycosylation and the effects of glycosylation on the aglycone solubility and general behaviour, including the absorption in tissues of man, prompted the synthesis of the isolated flavan glycoside. The uncertainty of the point of sugar attachment to the aglycone of some glycosides, especially with limited material available, further inspired the exploration of synthetic routes to glycosylated flavonoids. In an attempt to obtain the 5-O-glycosylated flavan, the selected glycosylation procedure was attempted on the analogous 5,7-dihydroxy-3',4'-dimethoxyflavanone, but proved unsuccessful because of the acidity of the 3-protons leading to ring opening. The same, procedure was attempted on the analogous chalcone with an unprotected A-ring. Glycosylations was successfully done on resacetophenone, phloroacetophenone and 4- methoxyphloroacetophenone as precursors to the formation of the glycosylated chalcone. However, the condensation with the appropriately protected benzaldehyde to obtain the glycosylated chalcone as precursor to the 5-O-glycosylated flavan was unsuccessful. The proposals that phenolic metabolites have physiological and therapeutic properties may also be associated with the compounds isolated from the tea. Luteolin and eriodictyol constitute part of the phenolic metabolic pool with a 3',4' -diol functionality which is claimed to have antioxidant activity. The antimicrobial activity of flavonoids in plants is also well documented and so is the antiviral activity of flavonoids and their ability to inhibit key enzymes in mitochondrial respiration. It was found that a C-2, C-3- double bond, a 4-keto group and a 3',4',5' -trihydroxylation of the B-ring are significant features of those flavonoids which show strong inhibition of NADH-oxidase. Coronary heart disease is also reported to be reduced in humans with high flavonoid intake. The anti-inflammatory and antitumor activity along with the ever-increasing interest in plant tlavonoids for treating human diseases and especially for controlling the immunodeficiency virus, the cause of AIDS, also attract interest in this herbal tea. These results clearly indicate that the claims of the health promoting properties of Honeybush tea may at least, in part, be attributed to the presence of these and other polyphenols in C. subternata. | en_ZA |
| dc.description.abstract | Afrikaans: Cyclopia subternata (Fabaceae), algemeen bekend as Heuningbostee, is een van nagenoeg 24 Cyclopia spesies endemies tot die Kaapse fynbos gebied van Suid Afrika. Met die rugsteuning van ons aanvanklike ondersoek op C intermedia wat die teenwoordigheid van n verskeidenheid fenoliese vebindings, insluitend kumestane, isoflavone, flavanone, xanthone, flavone, pinitol, p-kumaarsuur en flavonoïed glukosiede, aangedui het, geniet die tee huidiglik toenemende populariteit as gesondheidsdrankie. Die teenwoordigheid van hierdie verbindings, waaraan interessante farmakologiese eienskappe toegeskryf word, ondersteun deur die feit dat die tee baie min, indien enige, kaffeïn en lae tannieninhoud bevat, asook die medisinale gebruik van die tee deur die plaaslike bevolking in die Wes- en Oos-Kaap, het gelei tot hierdie voortgesette ondersoek na die inhoud van die subternata spesie. Opsomming Die asetoon en methanol ekstrakte van die ongefermenteerde lote van C. subternata het na chromatografiese skeidings (kolom met Sephadex LH 20 en preperatiewe dunlaag) n nuwe flavaan, flavonole, flavanone, flavone, isoflavone en C6.C1- en C6.C2-tipe verbindings gelewer. Die structure van die verbindings, as die volledige asetaat of gemetieleerde derivate, is met behulp van hoë-resolusie (300 MHz) ¹H KMR spektrometrie, (insluitend COSY, NOESY, HMQC, HMBC en DEPT l35° eksperimente) 13CKMR spektroskopie, Molekulêre Modellering en Sirkulêre dichroïsme bepaal. (+)-Pinnitol is saam met n nuwe apiofuranosiel(1"–›6")-glukopiranosiel karboksiel suur as nie-flavonoïed verbindings geïsoleer. Die aglikone behels epikatesjien-3-0-gallaat (flavanol), luteolien (flavoon), en orobol (isoflavoon). Die nie-flavonoïed glikosiede word verteenwoordig deur 'n 4-0-glikopiranosiel tyrosol, apiofuranosiel(1"–›6")- glikopiranosiel-bensaldehied en die asetaat derivate van twee nuwe O-glikosiede naamlik, 1-[β-D-2',3',4' -tri-O-asetielglukopiranosieloksi]-2-(3,5-diasetoksifeniel)etaan en l-asetoksi-2-(β-D-2',3',4' ,6' -tetra-O-asetielglukopiranosieloksi)etaan. Die flavonïed- O-glukosiede word verteenwoordig deur n nuwe 3',4',7-trihidroksi-5- (glukopiranosieloksi) flavan, die flavoon, scolymosied en die flavanone, hesperedien, narirutien en eriocitrien. Die C-glukosiede bestaan uit die xantoon, mangiferin, n C-6 kaemferolglukosied en twee nuwe C-glukosiede naamlik, 3,4',6,7-tetrahidroksi-5-(β-D-glukopiranosiel) flavanoon. Die sintese van die flavaanglukosied wat geïsoleer is, is gemotiveer deur die feit dat die flavaan nuut is, die bweerde gesondheidseienskappe van flavane in die algemeen en die relatief onverkende roetes na flavonoïedglukosiede. Die effek van flavonoïedglikosilering op die oplosbaarheid en gedrag van die aglikoon, die verbeterde opname in die weefsel van die mens asook die onsekerheid oor die posisie waar die suiker gekoppel is aan die aglikoon, gewoonlik wanneer min material beskikbaar is, het verder die beoogde sintese van die flavaan glikosied ondersteun. In n poging om die 5-0-flavaanglukosied te sintetiseer is die gekose glukosilerings prosedure op 'n analoë 5,7-dihidroksi-3',4'- dimetoksiflavanoon toegepas, maar was onsuksesvol as gevolg van die suurheid van die 3-protone wat tot ringopening lei onder basiese toestande. Dieselfde glikosileringsprosedure is gepoog op die analoë chalkoon met 'n onbeskermde A-ring. Glukosilerings is suksesvol uitgevoer op resasetofenoon, floroasetofenoon en 4- metoksifloroasetofenoon as substrate vir die vorming van die chalkoongl.ikosied. Die kondensasie van die asetofenoonglikosiede met die beskermde bensaldehied om die chalkoonglikosied as voorloper vir die flavaan glikosied te verkry, was egter ook onsuksesvol. Die voorgestelde fisiologiese en terapeutiese eienskappe van fenoliese metaboliete kan vereenselwig word met verbindings wat uit die tee geïsoleer is. Luteolien en eriodiktol vorm deel van die groep metaboliete met 'n 3',4'-diol funktionaliteit wat gekoppel word aan antioksidant aktiwiteit. Die antimikrobiese aktiwiteit van flavonoïede in plante is ook deeglik gedokumenteer en so ook die antivirale eienskappe en flavonoïede se vermoë om sleutel ensieme in die mitokondria respirasie te inhibeer. Daar is ook gevind dat n C-2, C- 3-dubbelbinding, n 4-keto groep en die 3',4',5'-trihidroksilering van die B-ring sleutel vereistes is vir die inhibisie van NADH-oksidase. Verder word beweer dat hartaanvalle verminder word onder mense met 'n hoë flavonoïedinname. Die anti-inflamatoriese en anti-kanker aktiviteit saam met die toenemende belangstelling in plant flavonoïede om siektes te behandel en ook om die Hl virus onder beheer te hou het 'n belang by hierdie tee aangewakker. Die resultate van hierdie ondersoek as geheelondersteun die vermoede dat die beweerde gesondheidsbevorderlike eienskappe van Heuningbostee ten minste gedeeltelik verband mag hou met die fenoliese inhoud van C. subternata. | af |
| dc.description.sponsorship | National Research Foundation (NRF) | en_ZA |
| dc.identifier.uri | http://hdl.handle.net/11660/6155 | |
| 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 | Cyclopia subternata | en_ZA |
| dc.subject | Fabaceae | en_ZA |
| dc.subject | Honeybush tea | en_ZA |
| dc.subject | Isoflavonoid | en_ZA |
| dc.subject | Glycosides | en_ZA |
| dc.subject | Flavan glycoside | en_ZA |
| dc.subject | Glycosylation | en_ZA |
| dc.subject | Flavanone | en_ZA |
| dc.subject | Flavan synthesis | en_ZA |
| dc.subject | Phenols | en_ZA |
| dc.subject | Flavonoids | en_ZA |
| dc.subject | Dissertation (M.Sc. (Chemistry))--University of the Free State, 2002 | en_ZA |
| dc.title | Structure and synthesis of polyphenols from cyclopia subternata | en_ZA |
| dc.type | Dissertation | en_ZA |