Doctoral Degrees (Chemistry)

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Struktuurondersoek van die isoflavanoïde uit Neorautanenia ficifolia (Benth ex Harv.) C.A. Sm.
(University of the Free State, 1965-01) Rall, Gerhardus Johannes Hendricus; Brink, C. v.d. M.
Abstract not available
Open Access
Homolitiese en heterolitiese splitsingsreaksies van disulfiedbindings
(University of the Free State, 1966-12) Janse van Rensburg, Nicolaas Jacobus
Afrikaans: Hierdie verhandeling behels 'n ondersoek van enkele splitsingsreaksies van die disulfiedbinding. 'n Aantal onsimmetriese disulfiede van lae molekulêre gewig, asook onsimmetriese disulfiede gevorm tussen proteïene wat tiolgroepe bevat en tiole van lae molekulêre gewig, is berei deur middel van tiol-disulfieduitruilingsreaksies. Die reaksie van sulfietione met bogenoemde onsimmetriese disulfiede is ondersoek. By meeste van die onsimmetriese disulfiede van lae molekulêre gewig toon sulfietione 'n groter affiniteit vir 'n spesifieke swaelatoom van die disulfiedbinding. Dit varieer van 'n geringe voorkeur tot 'n aanval wat feitlik uitsluitlik net op die een swaelatoom gerig is. Hierdie preferente aanval van sulfietione op n sekere swaelatoom word beheer deur stereochemiese faktore. Kwaternêre substitusie op β-koolstofatome veroorsaak groter steriese beskerming as tersiêre substitusie, terwyl laasgenoemde weer meer beskerming verleen as sekondêre substitusie. Die invloed van steriese verhindering is so sterk dat dit die invloed van faktore soos polarisasie van die disulfiedbinding, coulombiese kragte of die stabiliteit van die verplaasde merkaptiedione oorheers. Hoewel albei die β-koolstofatome van die onsimmetriese disulfiede tussen proteïen-tiolgroepe en sisteïen tersiêr-gesubstitueer is, toon sulfietione nogtans dikwels n groter affiniteit vir die "sisteïen"- swaelatoom. Die "proteïen"-swaelatoom van die onsimmetriese disulfied geniet steriese beskerming as gevolg van die geordende ruimtelike rangskikking van die natuurlike proteïenmolekule. Na denaturering deur ureum is die sekondêre en tersiêre proteïenstruktuur vernietig en val sulfiet die disulfied sonder enige voorkeure aan. In die bepaling van alifatiese tiole met Ellman se reagens, 5,5'-ditiobis-(2-nitrobensoësuur), (DTN), word onsimmetriese disulfiede in aansienlike hoeveelhede in die reaksiemengsel gevorm. So n onsimmetriese disulfied het feitlik dieselfde absorpsiespektrum as 5,5'-ditiobis-(2- nitrobensoësuur) en meng nie by die kolorimetriese bepaling van die gevormde l-karboksi-4-nitrotiofenol in nie. Die gevormde onsimmetriese disulfiede is nie stabiel in alkaliese medium nie en ontbind om 3-karboksi-4-nitrotiofenoli asook die ooreenkomstige alifatiese sulfien- en sulfoonsure te vorm. Ellman se reagens kan nie gebruik word om tiolgroepe van natuurlike keratien te bepaal nie maar wel na hidrolise. Deur karatienhidrolisate meganies te roer, kan die hidrolisetyd van 120 minute tot 45 minute verminder word. Onder hierdie kondisies gee die DTN-metode resultate wat in goeie ooreenstemming is met kontrolebepalings. Die kwantumopbrengs van sisteïen by sistiennatriumhipofosfietoplossings wat met ultravioletlig (golflengte = 254 mµ) bestraal is, is onafhanklik van die konsentrasie van die sistien, maar neem toe met toenemende hipofosfietioonkonsentrasies. Die reduksie van sistien deur hipofosfietione word geïnduseer deur 'n chemiese vry redikaalopwekker (Fe++/H202). Dieselfde twee intermediêre reaksieprodukte, (H2o-)PSR en [(H2o-)+PSR-]S-R, wat by die lig-geïnduseerde reaksie gevorm word, word ook in hierdie geval gevorm. Hoewel dié reaksie maklik verloop, word kwantitatiewe reduksie nie verkry nie. Die termies-geïnduseerde reduksie van sistien deur hipofosfietione verloop kwantitatief by pH 5.2, maar nie in 0.1 M HCl-medium of by pH 9.3 nie. Die induksietyd van bogenoemde reaksie word verminder deur toenemende hoeveelhede tiol by die reaksiemengsel te voeg.
Open Access
Die kondensasiereaksies tuusen pikoliensuur-n-oksiede en tosielesters
(University of the Free State, 1972-12) De Wet, Christiaan Rudolf; Roux, D. G.; De Villiers, P. A.
Afrikaans: Hierdie ondersoek is onderneem as 'n voortsetting van die ondersoek deur de Villiers van die reaksies van piridien-N-oksied met tosielchloried-en-tosielesters, asook om verdere lig te werp op die reaksies van pikoliensuur-N-oksiede. Die reaksie van α-pikoliensuur-N-oksied met 2-piridiel-p-tolueensulfonaat by verskillende temperature en in verskillende oplosmiddels is ondersoek. Die hoofprodukte in hierdie reaksies, soos uitgevoer in petroleumeter, is 2-hidroksipiridien en N-(2-piridiel)- piridoon-2 met kleinere hoeveelhede van 2,2-dipiridieleter, 2,3'-dipiridieleter en N-(4-piridiel)-piridoon-2. Hierdie reaksie is nog nie voorheen uitgevoer nie en in die vergelykbare reaksie van piridien-N-oksied-met 2-piridiel-p-tolueensulfonaat is nie 2-hidroksipiridien of 2,2-dipiridieleter as produkte verkry nie. Met toename in temperatuur het die hoeveelheid N-(2-piridiel)- piridoon-2 wat vorm, toegeneem, terwyl die hoeveelhede van al die ander reaksieprodukte afgeneem het. Sover vasgestel kon word is die invloed van temperatuur op hierdie tipe reaksies nog nie voorheen ondersoek nie. Wanneer die reaksie uitgevoer word in die teenwoordigheid van benseen word ook 2-fenielpiridien gevorm benewens die ander reaksieprodukte en in anisool word ook 2-p-anisolielpiridien gevorm. In In vergelykbare reaksie van piridien-N-oksied met 2-piridiel-p-tolueensulfonaat·onder dieselfde toestande is geen 2-fenielpiridien waargeneem nie. Hierdie reaksie is ook kineties ondersoek deur die tempo waarteen koolstofdioksied vrygestel is, te bepaal. Die resultate dui op 'n tweede-orde, eerste-orde-opeenvolgende reaksie. Wanneer α-pikoliensuur-N-oksied onder dieselfde toestande verhit word, is dit In eerste-orde reaksie met die vorming van piridien-N-oksied. Die snelheidskonstante vir die dekarboksilasie in anisool is bereken en volgens die resultaat verloop die reaksie vinniger in anisool as in etieleenglikol. Verder blyk dit dat α-pikoliensuur- N-oksied nie met 3-piridiel-p-tolueensulfonaat reageer nie. Hierdie resultaat stem ooreen met dié verkry in die reaksie van piridien-N~oksied met 3-piridiel-p-tolueensulfonaat. Wanneer In klein hoeveelheid water egter teenwoordig is, word 3-hidroksipiridien gevorm. Ten einde vas te stel of by die vorming van 2-hidroksipiridien die hidroksigroep aan die piridienkern van die suur óf dié van die ester heg, is die reaksie tussen α-pikoliensuur-N-oksied eh 5-metiel-2~piridiel-p-tolueensulfonaat ook ondersoek. Daar is vasgestel dat in hierdie reaksie slegs 2-hidroksi-5-metielpiridien, N-(2-piridiel)-5-metielpiridoon-2 en piridien-N-oksied gevorm is. Afgesien daarvan dat hierdie reaksie nog nie voorheen uitgevoer is nie, werp dit ook lig op die meganisme van hierdie tipe reaksies en is die, stowwe 5-metiel-2-piridiel-p-tolueensulfonaat asook N-(2-piridiel)-5~rnetielpitidoon-2 nog nie voorheen beskryf nie. In die reaksie tussen α-pikoliensuur-N-oksied en p-tolueensulfonielchloried in die teenwoordigheid van benseen is 2-hidroksipiridien en N-(2-piridiel)-piridoon-2 as hoofprodukte verkry, terwyl ook kleinere hoeveelhede 2-fenielpiridien, piridien, 2,2- dipiridieleter, N-(2-piridiel)-5-chloorpiridoon-2, N-(4-piridiel)- piridoon-2 en 3~piridiel-p-tolueensulfonaat gevorm is. In hierdie reaksie, soos voorheen uitgevoer, is slegs 2-hidroksipiridien, 2,2-dipiridieleter en piridien-N-oksied as produkte vermeld, terwyl in die vergelykbare reaksie met piridien-N-oksied onder dieselfde toestande geen 2-fenielpiridien verkry is nie. Hierdie reaksie is ook in die teenwoordigheid van m-dinitrobenseen uitgevoer ten einde vas te stelof 2-fenielpiridien volgens 'n ioniese-of vryradikaal-meganisme gevorm word. Die reaksie van nikotiensuur-N-oksied met 2-piridiel-p-tolueensulfonaat soos uitgevoer in petroleumeter lei tot die vorming van 2-hidroksinikotiensuur, 2-hidroksipiridien en N-(2--piridiel)- piridoon-2. Hierdie reaksie is nog nie voorheen uitgevoer nie en in die vergelykbare reaksie van nikotiensuur-N-oksied met asynsuuranhidried is nie 2-hidroksipiridien of N-(2~-piridiel)-piridoon-2 as produkte verkry nie. In die reaksie van isonikotiensuur-N-oksied en 2-piridiel-p-tolueensulfonaat is geen N-(2-piridiel)- piridoon-2 gevorm nie, maar slegs 2-hidroksipiridien en 2-hidroksi~is0nik0tiensuur. Hierdie reaksie is ook nog nie voorheen uitgevoer nie en die etielester van 2-hidroksi-isonikotiensuur is nie voorheen beskryf nie. In die vergelykbare reaksie van isonikotiensuur-N-oksied met asynsuuranhidried is geen 2-hidroksipiridien verkry nie. In Verbeterde metode vir die bereiding van 2-hidroksi-isonikotiensuur word beskryf. Die reaksies van die silwersout van 2-hidroksipiridien met 2-jodiumpiridien en met 2-broompiridien is ook onder verskillende toestande ondersoek. In die geval van 2-jodiumpiridien is 2,2~- dipiridieleter en N-(2~-piridiel)-piridoon-2 gevorm, terwyl in die geval van 2-broompiridien slegs 2,2~-dipiridieleter gevorm is. Sover vasgestel kon word is 2,2~-dipiridieleter nog nie voorheen op hierdie metode uit 2-broompiridien berei nie. Moontlike meganismes ter verklaring van die vorming van die reaksieprodukte word bespreek. In die geval van nuwe verbindings is k.m.r.- en massaspektra gebruik om die strukture daarvan te bevestig.
Open Access
Biflavonoied diastereo-isomere en hul biogenetiese voorlopers uit Berchemia SPP.: pogings tot sintese van analoe
(University of the Free State, 1976-02) Volsteedt, Francois du Rouan; Roux, D. G.
Afrikaans: Hierdie studie behels die struktuurondersoek, omskakelingsreaksies en pogings tot sintese van sommige van die mono- en biflavonoïede uit die kernhout van Berchernia zeyheri met 'n aanvullende studie op die kernhoutstowwe van die taksonomies notiverwante spesie; B discolor. Die verbindings uit B. zeyheri (rooi ivoor) kan in twee groepe geklassifiseer word, nl. mono- en biflavonoïede, almal op dieselfde 4' ,5,7- trihidroksi- (of sy ekwivalent) fenoliese patroon gegrond. Die eerste groep sluit die volgende in: maesopsin {2-(4-hidroksibensiel)-2,4,6-trihidroksibenso[b]furan-3(2H)-oon}; 7-metielmaesopsin (nnut); α,2’,4,4’,6’-pentahidroksicis- en trans-chalkoon; 2,3-trans-aromadendrin (3,4’,5,7-tetrahidroksiflavanoon); kaempferol (3,4’,5,7-tetrahidroksiflavoon); naringenin (4’,5,7-trihidroksiflavanoon) en 4,4’,6-trihidroksiauroon. Uit die beskikbare eksperimentele gegewens kon geen aanduiding van die struktuur van die rooi pigment wat verantwoordelik is vir die besondere voorkoms van die kernhout, verkry word nie. Die relatiewe hoë opbrengs van maesopsin het toegelaat dat verskeie nuwe omskakelings op die tetra-O-metieleter uitgevoer kan word met die doel om soortgelyke reaksies op daardie biflavonoïede, met een of meer maesopsineenhede waarvan genoegsaam verkry kon word, te herhaal. Reduksie met LiA1H4 het die ooreenstemmende 3-ol gelewer; brominering die 7-broomderivaat; en fotolise die 2’-hidroksi-α-metoksi-cis-chalkoonanaloog sowel as 1-(2-hidroksi-4,6-dimetoksifeniel)-2,2-dimetoksi-3-(4-metoksifeniel)-propan-1-oon. 2-(α-Asetoksi-4-metoksibensiel)-2,4,6-trimetoksi- en 2-(4-metoksibensoïel)-2-asetoksi-4,6-dimetoksibesno[b]furan-3(2H)-oon is vir die eerste keer verkry deur oksidasie van sintetiese 2’-hidroksi-α-metoksi-trans-chalkoon met Pb(0Ac)4 in asynsuur. Die struktuur van die cis- en trans-α-hidroksiechalkone is deur sintese en fotolitiese omskakeling bevestig. Die struktuur van die “konvensionele” chalkoon is deur sintese van 2’-hidroksi-4,4’,6’-trimetoksi-trans-chalkoon bevestig. Oksidasie van laasgenoemde met Pb(OAc)4 en Tl(NO3)3 lewer onderskeidelik tri-0-metielauroon en –isoflavoon. Al die biflavonoïede is nuwe natuurprodukte en sluit die volgende opties onaktiewe verbindings in (slegs triviale name genoem): zeyherin en isozeyherin, beide enantiomere pare bestaande uit twee I-2,II-7-gekoppelde bensokumaranonieleenheid verbind en neo- en isoneoberchenin wat slegs verskil t.o.v. die I-3,II-5-interflavonoïedbinding van voorafgaande twee. Al vier is enantiomere pare. ‘n Verdere biflavonoïed, rhamnin, saamgestel uit ‘n naringenieleenheid en ‘n terminale α-hidroksichalkooneenheid (I-3,II-3’-gekoppel), lewer vir die eerste keer direkte bewys (met die moontlikheid van ringopening in ag geneem) van inkorporasie van ‘n α-hidroksichalkoon as biogenetiese voorloper. Die bestaan van die verbinding dui aan dat ringsluiting van die terminale eenheid by berchenin en isoberchenin na intermolekulêre koppeling plaasvind. Twee verdure biflavonoïede, laktoon A en B genoem, identies aan die zeyherins behalwe dat die terminale eenheid (maesopsin) ’n bensielsuuromskakeling onder die toestande van metilering ondergaan het en derhalwe nie as natuurprodukte beskou word nie, is as enantiomorfe mengsels verkry. Hul dien egter as ‘n indirekte bewys vir α-hidroksichalkone as biogenetiese voorlopers, en dat siklisering by die zeyherins soos in die geval van berchenins moontlik eers na intermolekulêre koppeling geskied. Geeneen van die pare biflavonoïede ondergaan onderlinge omskakeling by ca. 150° (ontbinding) nie, sodat hul nie rotasie isomere verteenwoordig nie, maar wel diastereoisomere. Bibensokumaranonielmetaan, moontlik ‘n rotameriese mengsel volgens duplisering van seine in die KMR-spektrum van die 0-metieleter, bestaan uit twee maesopsineenhede, unike I-5,II-7 oor ‘n CH2-brug verbind. ‘n Verbinding verwant aan laasgenoemde, n. 2,7-bi(4-hidroksibensiel)-2,4,6-trihidroksibenso[b]furan-3(2H)-oon is ook geïsoleer. Al die biflavonoïede is uniek in die opsig dat hul 5-ledige heterosikliese ring(e) of ‘n α-hidroksichalkoon as eenhede bevat. As gevolg van ‘n gebrek aan material is slegs enkele omskakelings op sommige van die biflavonoïede uitgevoer. Reduksie van 0-metielzeyherin met KBH4 skakel slegs die karbonielgroep van die terminale eenheid na die alcohol om. Dieselfde resultaat is op die berchenins verkry. Fotolise van 0-metielzeyherin lei tot omskakeling van die terminale eenheid na ‘n ketalstruktuur soortgelyk as die verkry uit die fotolise van 0-metielmaesopsin. Deur die uitskakeling van suurtoestande en hitte is die 0-metieleters van maesopsin, zeyherin, isozeyherin, berchenin en isoberchenin na voltooiing van die ondersoek as opties aktiewe verbindings geïsoleer na metilering met diasometaan. In ‘n poging tot sintese van ‘n biflavonoïed is gevind dat wanneer ‘n gesubstitueerde fenol i.p.v. ‘n flavonoïedeenheid gebruik word onder toestande wat fenolkoppeling bevorder [alkalise K3Fe(CN)6], die reaksie van die verwagte afwyk deurdat koppeling in die β- i.p.v. die α-posisie van die chalkoon plaasvind. In die spesifieke geval koppel 2’,4-dihidroksi-4’,6’-dimetoksi-trans-chalkoon in die β-posisie met 3,5-dimetoksifenol in teenwoordigheid van K3Fe(CN)6 om vier diastereoisomere 2-[α-(4-hidroksi-2,6-dimetoksifeniel)-4-hidroksibensiel]-4,6-dimetoksiebenso[b]furan-3(2H)-one en 4’-hidroksie-4,6-dimetoksiauroon in goeie opbrengste te lewer. Die volgende verbindings is uit die kernhout van die verwante B. discolour geïsoloeer: maesopsin, alfitonien {2-(3,4-dihidroksibensiel)-2,4,6-trihidroksibenso[b]furan-3(2H)-oon}; α,2’,4,4’,6’-pentahidroksi- en α-2’,3,4,4’,6’-heksahidroksitrans-chalkoon (beide nuwe natuurprodukte); (-)-epi- en (+)-katesjien; kaempferol (3,4’,5,7-tetrahidroksiflavoon), kwersitien (3,3’,4’,5,7-pentahidroksiflavoon), 3,4’,5-trihidroksidihidrostilbeen, asook twee verbindings waarvan nog geen struktuurtoeseggings moontlik was nie. Fotolise van die heksametoksi-trans-chalkoon, derivaat van bogenoemde α-heksahidroksichalkoon, het die cis-isomeer gelewer. Slegs ‘n ketalanaloog is na die foto-oksidatiewe omskakeling van penta-0-metielalfitonien geïsoleer, in teenstelling met die addisionele cis-α-metoksichalkoon verkry by die fotolise van tetra-0-metielmaesopsin. Skrille kontras bestaan dus tussen die inhoudstowwe van die twee spesies. Benewens ‘n aanvullende katekoloksigeneringspatroon is die opvallendste egter die afwesigheid van die verwagte biflavonoïede by B. discolour op grond van taksonomiese verwantskap. Alhoewel twee α-hidroksichalkone in die kernhout voorkom dui die afwesigheid van biflavonoïede in teenstelling met die geval van B. zeyheri moontlik op ‘n verskil in die redokspotensiaal van die twee spesies se ensiemsisteme en/of dat ‘n α-hidroksichalkoon slegs tesame met ‘n “konvensionele” chalkoon, soos in die geval van rooi ivoor, as biogenetiese voorlopers vir biflavonoïede optree. Die aanwesigheid van α-hidroksichalkone en verwante hemiketale in hoë konsentrasie dui op ‘n chemotaksonomiese verwantskap tussen twee spesies.
Open Access
Totaalsintese en toksisiteit van 'n nuwe 12a-O-metielrotenoied: fitochemie van verwante isoflavonoiede
(University of the Free State, 1976-12) Oberholzer, Maria Elizabeth; Rall, G. J. H.
Afrikaans: Hierdie proefskrif behels die chemiese ondersoek van 'n reeks verwante natuurprodukte, waaronder 'n aantal fisiologies aktiewe rotenoïede, uit die bol van Neorautanenia amboensis. Tydens die ondersoek is daar ook gepoog om 'n voorstelling, gebaseer op biogenetiese grondslag, van die onderskeie komponente daar te stel. Die relatiewe toksisiteit van sintetiese en natuurlike rotenoïede is bepaal deur die snelheid van inhibisie van sitochroom-c-reduktase te volg terwyl 'n moontlike korrelasie tussen giftigheid en struktuur bespreek word. N. amboensis behoort tot die Leguminosae plantfamilie wat in Suider Afrika verteenwoordig word deur sleg s 'n paar spesies, wat bekend is vanwee die gebruik as visgif van veral N. ficifolia en N. amboensis. Hierdie aktiwiteit het as stimilus gedien tot die chemiese ondersoek van die plant. Met die toenemende kommer oor besoedeling en die leemte wat ontstaan het met die verdwyning van gechlorineerde insektisiede van die mark, het die vraag na geskikte plaasvervangers, onder andere rotenoon, skerp gestyg veralomdat die toksisiteit van rotenoïede deur oksidatiewe prosesse heeltemal verdwyn na slegs enkele dae en dus geen besoedelingsgevaar inhou nie. Met behulp van tweedimensionele dunlaag- en papierchromatografie is bepaal dat die benseen- en metanolekstrakte van die plantmateriaal baie komplekse mengsels is en voorlopige skeidings is uitgevoer deur kolomchromatografie en 'n teenstroomverdeling. Die isolasie en struktuuropklaring van opties aktiewe (-)-(6aS, 12aS)-neobanoon en (-)-(6aS, 12aS)-12a-hidroksi-isomillettoon, twee 12a-gesubstitueerde rotenoïede, en die bevinding dat beide 'n hoë mate van toksisiteit teenoor Lucilia serieata vertoon, het daartoe gelei dat die sintese van neobanoon volgens 'n biogeneties georïenteerde roete (chalkoon→isoflavoon→rotenoïed 12a-gesubstituteerde rotenoïed) aangepak is. Die sintese van neobanoon verteenwoordig die eerste totaalsintese van 'n 12a-O-metielrotenoied. Tydens die sintese is 'n baie bruikbare bydrae gelewer in die vorming van komplekse chalkone deur die aanwending van "Crown" eters. Benewens die isolasie van struktuurvariante van isoflavone, pterokarpane en rotenoïede, het hierdie ondersoek ook gelei tot die identifisering van die eerste natuurlike opties aktiewe isoflavan-4-ol, (+)-ambanol. Aan die hand van PMR-spektroskopie is aangetoon dat ambanol die 3,4-cis konfigurasie besit. Die struktuur is bevestig deur totaalsintese en omskakelingsreaksies. Identifikasie van hierdie verbinding is van besondere belang, aangesien dit 'n sleutelrol vervul in die biosintese van pterokarpane en by die oksidatiewe interomskakelbaarheid van isoflavonoiede. Die bol van N. amboensis bevat ook drie lede van die seldsame groep 2S-5-deoksi-flavonoïede, naamlik (-)-3',4',7-trihidroksi-2,3-transflavan-3,4-cis-diol, (-)-3',4',7-trimetoksi-2,3-trans-flavan-3,4-cis-diol en (-)-3,3',4,4'7-pentametoksi-2,3-trans-3,4-cis-flavaan waarvan laasgenoemde ‘n nuwe natuurprodruk verteenwoordig. Die struktuur en stereochemie van laasgenoemde korreleer met spektrometriese analises en is bewys deur omskakeling van eersgenoemde twee verbindings na die pentametoksiderivaat. Die gesamentlike voorkoms van flavonoïede en isoflavonoïede in N. amboensis is van biogenetiese belang, aangesien hierdie verskynsel daarop dui dat flavonoïed en isoflavonoïed biosintese langs gelyksoortige weë kan geskied. Die pterokarpaanskelet en substitusiepatroon van (-)-(6aR, llaR)- neobanol, ‘n nuwe 12a-hidroksipterokarpaan, is bepaal met behulp van PMR- en massagegewens terwyl die chemiese omskakeling na ‘n pterokarpeen die struktuur onteenseglik vasgelê het. 2’7-Dimetoksisophorol en 2’-hidroksi-2-metoksi-4’,5’-metileendioksi- 6,7,4",5"-furanoisoflavanoon is twee nuwe isoflavanone waarvan laasgenoemde nie alleen die eerste 2-metoksi-isoflavanoon is nie, maar ook die eerste verbinding in hierdie klas verteenwoordig wat optiese aktiwiteit vertoon. PMR- sowel as MS-gegewens is in ooreenstemming met die voorgestelde strukture en bevestig die onderskeie substituente. Twee nuwe isoflavoonglikosides, daidzein-7-D-xilosiel-β-D-glukosied en genistein-7-D-xilosiel-β-D-glukosied, is in relatief hoë konsentrasies geïsoleer. Die aglikoongedeeltes is met behulp van PMR- en MS-spektrometrie gekarakteriseer terwyl die suikers deur middel van hul trimetielsilieleters gaschromatografies bepaal is. Buitengewoon eenvoudige metaboliete, 6-hidroksi-2,3-dihidrobensofuraan, α-OH, α:5(6-metoksi-2,3-dihidrobensofuraan)-etaan en p-metoksiasetofenoon, tot op hede onbekend in natuurlike bronne, is uit N. amboensis geïsoleer. Met betrekking tot die strukture bied hierdie bevindings geen nuwigheid nie, maar die natuurlike voorkoms daarvan mag wel belangrike biogenetiese implikasies inhou, aangesien p-metoksi-asetofenoon moontlik as voorloper tot retrochalkone kan dien. Nadat voorlopige toksisiteitsbepalings belowend geblyk het, is twaalf verskillende rotenotede getoets met betrekking tot inhibisie van die mitochondriële nikotienamiedadeniendinukleotied oksidasie in die asemhalingstelsel. Met behulp van kinetiese studies kon bepaal word dat rotenoon, natuurlike neobanoon en 12a-hidroksi-isomillettoon van vergelykbare toksisiteit is terwyl dit aan die lig gekom het dat die stereochemie van rotenoïede (6aS, 12aS) 'n bepalende faktor is ten opsigte van hul inhibisievermoë van die mitochondriële elektronvervoersisteem. Hierdie bevinding is gerugsteun deur die feit dat sintetiese, (±)-neobanoon 'n baie laer fisiologiese aktiwiteit as die natuurproduk toon, asook deur die verskynsel dat (-)-cis-12a-hidroksirotenoon die enigste isomeer van die vier 12a-hidroksirotenoondiastereoisomere is wat toksisiteit vertoon.
Open Access
Modelverbindings in tanniensintese: die konformasie van vryfenoliese eenhede
(University of the Free State, 1980-12) Pretorius, Pierre Johann; Roux, D. G.; Ferreira, D.
Afrikaans: Die basiese doelwitte van hierdie studie is essensieel tweërlei van aard naamlik: (i) fragmentering van die heterosikliese eterbinding in 'n flavan-3-ol, as model vir die fundamentele bousteen van tanniene, gevolg deur die koppeling van 'n hidrofobiese tipe nukleofiel om sodoende enersyds die molekule te aktiveer ten opsigte van nukleofiliteit vir reaksie met formaldehied en andersyds wateroplosbaarheid te verlaag en (ii) die koppeling van fenoliese eenhede met bensiliese oksigenering onder milde suurkondisies aan die C4-karbokatioon van flavan-3,4-diole, as modelreaksie vir die sintese van biflavonoïede met terminale 3,4-diol funksionaliteit en ter bestudering van die konformasie van die heterosikliese ring van 4-ariel-/ -flavanielflavan-3-ole. Reaksie van (+)-katesjien met natriumsianied lewer 'n basisgekataliseerde herrangskikkingsproduk, katesjiensuur. Hierdie produk ontstaan deur onverwagse opening van die heterosikliese ring onder invloed van elektronvrystelling deur die 4-fenolaatioon en herrangskikking via In 1,6-tipe Michael addisie van C8 van die A-ring en die intermediêre kinoonmetied. Onder relatief drastiese kondisies reageer (+)-katesjien met swaeldioksied om uitsluitlik 'n dimeriese kondensasieproduk te lewer. Struktuurbewys hiervoor bevestig vir die eerste keer die postulaat van Freudenberg rakende die selfkondensasie van flavan-3-ole. Suurgekataliseerde koppeling van (+)-mollisacacidien en floroasetofenoon lewer beide die 3,4-trans- en 3,4-cis-4-arielflavan-3-oIe. Soortgelyke koppeling van (+)-mollisacacidien en (+)-taksifolien lei tot vorming van die 4,β-gekoppelde alles trans isomeer in uiters lae opbrengs. Onder dieselfde en selfs meer drastiese kondisies kon egter geen koppeling tussen (+)- mollisacacidien en (+)-fustien verkry word nie. Die KMR-spektra van sommige van die vryfenoliese 3,4-cis-4-arielflavan-3-ole dui op 'n abnormale klein koppelingskonstante tussen H2 en H3. Hierdie lae waarde word geïnterpreteer op grond van 'n afwyking van die normale vyfpunt-koplanêre konformasie van die heterosikliese ring as gevolg van die neiging van beide C2- en C4-fenielsubstituente om 'n ekwatoriale posisie in te neem en sodoende die heterosikliese ring in 'n verwringde bootkonformasie te forseer. Dit blyk dus dat verdere verfyning van reaksiekondisies waarskynlik sou kon lei tot sintese van biflavanolede met terminale diolfunksionaliteit terwyl 'n groter reeks vryfenoliese 4-arielflavan-3-oIe benodig word ten einde die konformasie van die heterosikliese ring finaal vas te stel.
Open Access
Profisetinidiene: die eerste sintese van tetraflavanoiede: bi- en triflavanoiede met terminale diolfunksie
(University of the Free State, 1984-01) Young, Desmond Austin; Roux, D. G.; Ferreira, D.
Afrikaans: Chemici in die flavanoiedveld leun swaar op spektroskopiese metodes ter ontrafeling van die komplekse strukture van bi- en hoëre flavanoiede. Die kragtigste van hierdie tegnieke naamlik ultra-hoë resolusie 1H en 13C kmr-spektrometrie gaan egter mank aan sekere inherente tekortkomings op veral die tetraflavanoiedvlak vanweë veral die abnormale hoë temperatuurvereistes (>200'C) om vinnige rotasie om die onderskeie interflavanoiedbindings en aldus skerpgedefinieerde spektra te induseer. Hierdie probleme het die behoefte aan sintetiese toegang tot oligomeriese tanniene beklemtoon en verteenwoordig hierdie studie dus primêr 'n ekskursie ten opsigte van die bepaling van koppelingsvolgorde en stereochemie van tetraflavanoiede deur middel van sintese. 'n Herondersoek van die komplekse fenoliese mengsel van die kernhout van A. mearnsii het verskeie 'nuwe' produkte gelewer. 'n Pienk band vanaf sellulose kolomme (lae mobiliteit met water as eluant) het onder andere 'n nuwe dioksaantipe bifisetinidol met 2,3-trans-3,4-trans:2,3-trans-3,4-cis stereochemie gelewer. Sintese van die dioksaantipe biflavanoied is vanaf tri-O-metiel-(+)-mollisacacidien met BF3 as katalisator uitgevoer. Die sintese het, benewens die genoemde isomeer, die bekende 3,4-alles-cis dioksaan biflavanoied as hoofproduk gelewer tesame met 'n 2,3-cis-3,4-cis:2,3-trans-3,4-cis analoog en twee [4,6]-C-C-gekoppelde triflavanoied dioksane waarvan die stereochemie van die 6-flavanieleenhede as 3,4-trans en 3,4-cis onderskeidelik bepaal is. Uit dieselfde fraksie is 'n nuwe 3,8,9-trihidroksidibenso-a-piroon, 3,9,1o-trihidroksidibenso-a-piroon en 'n komplekse dibenso-a-piroon identies aan dié uit Umtiza Zisterana vir die eerste keer uit A. mearnsii verkry. Die isolasie van laasgenoemde reeks verbindings beklemtoon opnuut die kompleksiteit van die metaboliese poel van Acacia mearnsii. Om insae te kry in sommige aspekte van die meganisme van flobafeenvorming, is die [4,8]-3,4-trans(-)-fisetinidol-(+)-katesjien biflavanoied in asynsuur/monochloorasynsuur/etanol vir 24 uur onder stikstof gerefluks. Bewyse vir splyting van die interflavanoïedbinding is verkry deur isolasie van(+)-katesjien, [4,6] -trans- en cis-biflavanoïede (1,3-flavanielmigrasie) en twee angulêre triflavanoiede. Hierdie produkte word vergesél deur twee verbindings waarin die heterosikliese ring van die (-)-fisetinidoleenheid herrangskikking ondergaan het. Herrangskikking vind plaas deur aanval van O7 van die (+)-katesjieneenheid op C2 van die O-geprotoneerde C-ring om verbindings van beide retensie en inversie van konfigurasie op die betrokke koolstof te lewer. Hierdie herrangskikking het effektief die 'vrystelling' van die resorsinol A-ring van die (-)-fisetinidoleenheid tot gevolg met gepaardgaande verhoogde nukleofiliteit en aldus verhoogde dryfkrag vir kondensasie na onoplosbare en hoogsgekondenseerde tanniene (ekwivalent van flobafeenvorming). 'n Noukeurige herondersoek na die kondensasiereaksie van (+)-katesjien met (+)-mollisacacidien het al vier moontlike isomere gelewer wat die vermoede bevestig dat die [4.6]-cis produk in 'n vorige ondersoek oor die hoof gesien is. 1H kmr (80MHz) spektra (σDMSO 150'C) het spesifieke diagnostiese patrone aangedui. naamlik dat ∆σH H 2 - 3 vir die F-ring (+)-katesjieneenheid) groot is (0.61) vir [4.8]-cis koppeling en klein (0.14) vir [4.8]-trans koppeling. Uitbreiding hiervan na die angulêre triflavanoiede uit A. mearnsii bevestig hierdie waarneming en dui daarop dat soortgelyke parameters ook vir hoër oligomere geldig is. Reaksie van (+)-katesjien met die vryfenoliese triflavanoied fraksie uit A. mearnsii het drie produkte gelewer waarvan twee [4. 6] en [4, 8] -gekoppel, in ooreenstemming is met verwagte strukture gebaseer op 3,4-cis:3,4-trans:3,4- trans-stereochemie van die diol triflavanoied. Die derde produk dui daarop dat 'n tweede diol triflavanoied met 'n 3,4-trans:3.4-trans-interflavanoied stereochemie waarskynlik in bogenoemde fraksie teenwoordig is. Weens gebrek aan materiaal kon die struktuur van die kondensasie produkte egter slegs gedeeltelik bepaal word. Om as modelle te dien vir hoër oligomere, is (+)-katesjien aan die diolbiflavanoiede gekoppel. Dit is opmerklik dat 3,4-ois interflavanoied stereochemie van die diolbiflavanoïede uitsluitlik 3,4-trans aansluiting met (+)-katesjien en 3,4-trans interflavanoied stereochemie, 3,4-cis aansluiting tot gevolg gehad het. Hierdie waarneming kan slegs gedeeltelik verklaar word aan die hand van die rigtende invloed deur die A-ring van die [6]-flavanieleenheid op koppeling van (+)-katesjien aan die elektrofiele C4-sentrum. Struktuurbepaling van tetraflavanoiede uit A. mearnsii het tekortkominge in kmr-tegnieke blootgelê, aangesien die koppelingspunt van die bifisetinidoleenheid aan die ten volle gesubstitueerde A-ring van die (+)-katesjieneenheid nie bepaal kan word nie en vanweë die hoë temperatuurvereistes om vinnige rotasie en dus 'skerp' kmr-spektra te bewerkstellig. Sintese van tetraflavanoïede is dus aangepak om die strukture van die geïsoleerde analoë te bepaal. Toegerus met kennis van stereochemie via sintese, kon 80MHz kmr sinvol benut word om karakteristieke kmr-patrone te identifiseer en sodoende redelik volledig kmr-interpretasie moontlik te maak. SD-spektra van die meerderheid van die hoëre oligomere het getoon dat die stereochemie van die koppelingspunt aan (+)-katesjien in die lineêre tri- en tetraflavanoiede die teken van die lae golflengte hoë-intensiteit Cotton-effek bepaal. Vir meeste van die 'angulêre' tetraflavanoiede het dit geblyk dat die stereochemie van die Ca koppelingspunt van (+)-katesjien soortgelyk die teken van die Cotton-effek bepaal. Hoewel normale koppelingskonstantes waargeneem word, is uitsonderings egter verkry wat daarop wys dat die SD-metode met huidige korrelasies nie op hoër oligomeriese vlak met dieselfde vertroue as op biflavanoied vlak toegepas kan word nie. 13C kmr-spektrometrie van sommige profisetinidiene dui daarop dat C4-kwasi-aksiale-(3,4-cis)-lavanielgroepe 'n Y skermende effek op C2 relatief ten opsigte van die ongesubstitueerde koolstof uitoefen, terwyl C4-kwasi-ekwatoriale groepe 'n y ontskermende effek uitoefen. Op die vryfenoliese (-)-fisetinidol-(+)-katesjien profisetinidiene kan die koppelingspunt aan (+)-katesjien afgelei word. Koppeling aan 'n spesifieke koolstof het ontskerming van daardie koolstof tot gevolg met 3,4-trans stereochemie wat 'n groter mate van ontskerming as in die geval van die 3,4-cis analoog veroorsaak. Op die metieleterdiasetaatvlak word 13C kmr-spektra egter ook gekompliseer deur beperking op rotasie om die interflavanoiedbinding en word studies by verhoogde temperatuur benodig alvorens sinvolle interpretasie en ekstrapolering na hoër oligomere moontlik is.
Open Access
Sintese en konformasie van natuurlike flobatanniene: die meganisme van basisgekataliseerde piraanherrangskikkings
(University of the Free State, 1988-12) Steynberg, Jan Petrus; Ferreira, D.; Brandt, E. V.; Young, D. A.
Afrikaans: Guibourtia coleosperma (Rhodesian copalwood) is bekend as 'n harde en duursame houtsoort wat opvallend weerstand teen verrotting bied. Die onlangse isolasie van unieke bi- en triflavanoïede gebaseer op leukoguibourtinidiene (4',7-dihidroksiflavan-3,4-diole) en fenoliese stilbene, bekend vir antifungiese eienskappe, het as stimulus gedien vir 'n herondersoek van die fenoliese metaboliete. Uitgebreide verrykings- en skeidingstegnieke lewer, benewens bekende (E)-stilbeen monosiede, die unieke 4',5-dimetoksi- en 3',5-dihidroksi-4'-metoksi-3-[O-α-L-rhamnopiranosiel-(1 - 6)-β-D-glukopiranosieloksil stilbeenbiosiede. Die lae konsentrasie van hierdie verbindings het 'n nuwe benadering ten opsigte van identifikasie genoodsaak. Ontwikkeling van 'n elegante metode waar die aard en posisie van interglikosidiese-sowel as glikosied-aglikoon bindings met behulp van n.O.e. tegnieke ('H k.m.r.) gekarakteriseer word, voorsien 'n waardevolle bydrae tot identifisering van glikosiede. Hierdie metode het veral meriete waar alternatiewe spektroskopiese en chemiese metodes deur die beskikbaarheid van voldoende materiaal aan bande gelê word. Die stilbeenglikosiede word in G. coleosperma vergesel deur flobatanniene, 'n unieke klas van ring-geïsomeriseerde tanniene. Hierdie verbindings verteenwoordig die produkte van stereospesifieke ring-isomerisasie van 2,3-trans-3,4-trans- en stereoselektiewe isomerisasie van 2,3-trans-3,4-cis-(-)-fisetinidol eenhede in konvensionele (4,8)-bi- en (4,6:4,8)-triflavanoïede. Fisiese data soos massaspektroskopie, sirkulêre dichroisme maar veral hoë resolusie 1H k.m.r. n.O.e. tegnieke, lei, op enkele uitsonderings na, tot volledige struktuuropklaring van die gefunksionaliseerde tetrahidro-2H,8H-pirano [2,3-h]-, [2,3-f]- en [2,3-g] asook heksahidro-2H,6H,10H-dipirano[2,3-f:2',3'-h] chromene. Eenduidige struktuurbewys vir die nuwe klas van gekondenseerde tanniene volg uit piraanherrangskikkings van die waarskynlike biflavanoiedvoorlopers onder milde basiese kondisies (pH1O) . Die vatbaarheid van biflavanoiede onder basiese kondisies vir epimerisasie en herrangskikking via kinoonmetiede kompliseer egter die reaksieverloop. Om dus newereaksies geassosieer met 'n E-ring kinoonmetied uit te skakel, is die 4-0-metieleterderivate (E-ring) van die biflavanoiede aan die basiese reaksiekondisies blootgestel. Terwyl biflavanoiede met 2,3-trans-3,4-trans-flavan-3-ol "boonste" eenhede vatbaar is vir relatief stadige maar stereospesifieke C-ring isomerisasie, ondergaan die analoë 2,3-trans- 3,4-cis isomere stereoselektiewe isomerisasies teen 'n verhoogde tempo. Laasgenoemde analoë is verder vatbaar vir herrangskikkings na tetrahidropiranochromene waar die pirokatekol B- en resorsinol A-ringe omgeruil is relatief tot die posisies daarvan in die "normale" isomere. Hierdie ringomruilings geskied via 1,3-flavanielmigrasie in intermediêre kinoonmetiede en gaan gepaard met die inversie van die absolute konfigurasie by die ekwivalent van 3-C (C-ring) in die biflavanoied voorloper. Opvallend is dat sommige van hierdie "ringomgeruilde " analoë ook in Baikiaea plurijuga aangetref is wat vermoedelik dui op die funksionering van 'n meganisme in die natuur soortgelyk as dié voorgestel in hierdie ondersoek. Benewens die voorsiening van eenduidige struktuurbewys vir die volledige reeks natuurlike flobatanniene, is 'n aanvaarbare meganistiese verklaring vir die verloop van die basisgekataliseerde piraanherrangskikkings ontwikkel. Die benadering van selektiewe beskerming van 4-OH(E), het verder afdoende bewys verskaf dat die waargenome flavanielmigrasies by die "onbeskermde" analoë via 'n E-ring kinoonmetied verloop. In teenstelling met "beskermde" biflavanoïede waar slegs die C-ring aan isomerisasie onderworpe is, kan beide die C- en I-heterosikliese ringe van 'n triflavanoïed piraanherrangskikking ondergaan. Behandeling van die (4α,8:4α,6)-bis-(-)-fisetinidol-(+)-katesjien as prototipe vir trimeriese profisetinidiene met basis het inderdaad die heksahidro-2H,6H,lOH-dipirano[2,3-f:2' ,3'-h] chromeen wat dui op 'n dubbele ringisomerisasie asook isomerisasie-intermediêre 6-flavaniel-[2,3-h]- en 1O-flavaniel-[2,3-f] chromene waar slegs een heterosikliese ring isomerisasie ondergaan het, gelewer. Die 10-flavaniel-[2,3-f] chromeen is ook uit G. coleosperma geïsoleer terwyl die dipirano[2,3-f:2' ,3'-h'] chromeen uit Colophospernum mopane geïsoleer is. Ten spyte van intensiewe ondersoeke na kommersiële basisgekataliseerde reaksies van prosianidiene met die oog op benutting van kommersiële ekstraksie van "loblolly pine" bas onder basiese kondisies, bestaan geen getuienis van C-ring isomerisasies by hierdie kommersieel-belangrike klas verbindings nie. Behandeling van prosianidien B-3, 'n tipiese prosianidien biflavanoïed, met milde basis lei tot 'n tetrahidropirano[2,3-h] chromeen met "omgeruilde" floroglusinol A- en pirokatekol B-ringe asook analoë 4-ariel-2- flavaniel bensopirane d.w.s. analoë waarin die 4-C (+)-katesjienen die 2-C pirokatekoleenheid "uitruil". Terwyl die tetrahidropiranochromeen vorm deur 1,3-flavanielmigrasie in 'n intermediêre kinoonmetied, ontstaan die 4-ariel-2-flavanielbensopirane deur 1,3-migrasie van 'n "vrygestelde" floroglusinoleenheid in dieselfde kinoonmetied intermediêr. Onder hierdie milde basiese kondisies kon geen bewyse vir omskakeling na "catechinic-acid" tipe produkte verkry word nie. Hierdie verbindings is bekend vir buitengewone suurheid en lae reaktiwiteit teenoor aldehiede en het die suksesvolle toepassing van alkaliese ekstraksie van natuurlike prosianidiene tot dusver gekortwiek. Die huidige ondersoek bewys dus dat met die versigtige seleksie van kondisies hierdie probleme grootliks oorbrug kan word. Die afwykende 1H k.m.r. en SD data van tetrahidropiranochromene met trans-trans C-ring konfigurasie en die omgekeerde Cotton-effek van [2,3-h] chromene met 2,3-trans F-ring konfigurasie, het die toekenning van absolute konfigurasie by sekere verbindings gekompliseer. So toon die SD spektra van die produkte met "omgeruilde" resorsinol A- en pirokatekol B-ringe 'n sterk negatiewe Cotton-effek in teenstelling met 'n verwagte positiewe Cotton-effek deur toepassing van die aromatiese kwadrantreël. Die teenstrydige chiroptiese gedrag word aan die konformasionele mobiliteit van die F-ring toegeskryf en is in 'n poging om die probleem te oorbrug die volgende benaderings benut. Die geredelike-beskikbare 4-arielflavan-3-ole is in modelreaksies gebruik om ondubbelsinnig te bewys dat ringomruiling tydens die isomerisasiereaksie met inversie van die absolute konfigurasie by die chirale sentra van die C-ring gepaard gaan. Laastens is die konformasionele gedrag van die flobatanniene teoreties met rekenaargesimuleerde molekulêre meganika bestudeer en kon deur die SD data met teoreties voorspelde voorkeurkonformasies in verband te bring die afwykende chiroptiese gedrag van sekere flobatanniene sinvol verklaar word. Uit Dreidingmodelle blyk dit duidelik dat 'n dominante A-konformasie, soos deur MM-berekenings bevestig, by tetrahidropiranochromene met alles-trans C-ring konfigurasie tot 'n "omgekeerde" Cotton-effek sal lei. Die konformasionele mobiliteit van die F-ring by tetrahidropiranochromene met 2,3-trans F-ring konfigurasie word inderdaad deur MM-berekenings bevestig (E:A konformeerverhouding, + 50:50). Uit die oogpunt van die kommersiële benutting van gekondenseerde tanniene is bogenoemde C-ring isomerisasie met gepaardgaande "vrystelling" van 'n resorsinoleenheid van fundamentele belang. Die vrygestelde resorsinolring behoort tot die aktivering van die basiese tannienskelet, veral vanaf die triflavanoiedvlak, vir reaksie met bv. formaldehied te lei om aldus aanleiding te gee tot beter benutting van tanniene in die koudsettende kleefstofbedryf.
Open Access
Struktuur en sintese van prorobinetinidien- en prosianidientipe gekondenseerde tanniene
(University of the Free State, 1992-02) Cronje, Annemarie; Steynberg, J. P.; Ferreira, D.; Brandt, E. V.
Afrikaans: Die wye kommersiële toepassing van die 'Mimosa' ekstrak van die tannienryke bas van Acacia mearnsii het as stimulus vir die eerste fitochemiese ondersoek van die fenoliese komponente in die nywerheidsgedroogde bas gedien. Toepassing van uitgebreide verrykings- en skeidingstegnieke lewer benewens die bekende mono-, di- en trimeriese voorlopers, die flavan-3-ol, epirobinetinidol, prorobinetinidien biflavanoïede met 3,4-cis relatiewe konfigurasie, (-)-robinetinidol-(4β,8)-(+)-gallokatesjien en (-)-robinetinidol-(4β,8)-(+)-katesjien, 'n A-tipe prorobinetinidien, (-)-robinetinidol-(2β - 7; 4β - 8)-(+ )-katesjien en 'n C-gealkileerde profisetinidien, (-)-fisetinidol-( 4α,8)-6-metiel-(+)-katesjien. Hierdie metaboliete word deur 'n reeks unieke prorobinetinidienverwante ringgeïsomeriseerde tanniene vergesel. Struktuurbepaling is gedoen deur benutting van hoe resolusie 'H k.m.r. n.O.e. tegnieke, sirkulere dichroïsme (SD), massaspektrometrie (MS) en is waar moontlik deur sintese, d.i. die basisgekataliseerde omskakeling (pH 10) van biflavanoïedvoorlopers, bevestig. Weens die vatbaarheid van biflavanoïede vir C-2-epimerisasie en herrangskikking via kinoonmetiede onder basiese kondisies is die 3',4'- en 4'-O-metieleterderivate (E-ring) van die biflavanoiedvoorlopers geselekteer vir 'n studie van hul basisgekataliseerde herrangskikking. Die piraanherrangskikkingsreaksie van (-)-robinetinidol-(4β,8)-(+)-katesjien mono-O-metieleter lewer 'n A-tipe prorobinetinidien, (-)-robinetinidol-(2β - 7; 4β - 8)-(+)-katesjien, met spektroskopiese data identies aan die van die natuurproduk. Hierdie verteenwoordig nie slegs die eerste A-tipe van die 5-deoksi (A-ring) oligoflavanoïede nie, maar ook die eerste in die klas van proantosianidiene met 'n 3,4-cis relatiewe konfigurasie van die C-ring. Die omskakeling van 'n B-tipe proantosianidien na 'n A-tipe analoog word in terme van die oksidatiewe verwydering van 'n hidriedioon by C-2( C) verklaar. Die rol van atmosferiese suurstof in hierdie oksidatiewe transformasie blyk duidelik uit 'n vergelykende basisgekataliseerde reaksie waarin spesiale voorsorgmaatreëls getref is om suurstofvrye kondisies te skep. Stereoselektiewe isomerisasies asook herrangskikking waartydens die pirogallol B- en A-ringe omruil t.o.v. die posisies in die 'normale' isomere, lewer die verwagte ringgeïsomeriseerde produkte en slegs klein hoeveelhede van die A-tipe analoog. Die 'H k.m.r. spektrum van die A-tipe proantosianidien met 3,4-cis relatiewe konfigurasie (C-ring) toon identiese koppelingskonstantes (J3,4 3.5 Hz) in vergelyking, met die van analoe met 3,4-trans stereochemie. Hierdie waarneming kan aan die konformasionele starheid van die bisikliese sisteem wat tot identiese dihedriese hoeke tussen 3-H(C) en 4-H(C) aanleiding gee, toegeskryf word. 'n Metode gebaseer op die hoogs selektiewe 'H n.O.e. assosiasie van 3-H(C) is ontwikkel waarvolgens die 3,4-trans en 3,4-cis isomere ondubbelsinnig onderskei kan word. Die basisgekataliseerde piraanherrangskikkingsreaksie van die 'beskermde' triflavanoïed voorloper, (4α,8: 4(α,6)-bis-(-)-ro binetinidol-(+)-katesjien di-O-metieleter lewer na 'n kort reaksietyd slegs die intermediere, 10-flavaniel[2,3f]- chromeen. Hierdie flobatannien is uit die kommersiële A. mearnsii-ekstrak geïsoleer en ontstaan via 'n enkele hoogs stereoselektiewe ringisomerisasie. Die basisgekataliseerde C-ring isomerisasies is ook uitgebrei om 'n reeks piranochromene verwant aan (-)-fisetinidol-(-)-epikatesjien biflavanoïede in te sluit. Die natuurlike voorkoms van 'n reeks flobatanniene met beide (+)- en (-)-epikatesjien sowel as (+)- en (-)-katesjien as tenninale eenhede, tesame met die waarneming dat die koppelingskonstantes (J2,3 ca. 1.0 en ca. 7.0 Hz onderskeidelik) vir die heterosikliese protone differensiasie bemoeilik, het die noodsaaklikheid van sintese beklemtoon. Die strukture van 'n reeks natuurprodukte uit Guibourtia coleosperma, Colophospermum mopane en Baikiaea plurijuga is aldus volgens hierdie protokol bevestig. Ondersoek is verder ingestel na reduktiewe degradasietegnieke ten einde die probleme rakende die struktuurbepaling van A-tipe proantosianidiene en veral die bepaling van die stereochemie van die terminale flavan-3-ol eenhede van hierdie klas van proantosianidiene uit te klaar. Vanwee verskeie kompliserende faktore byvoorbeeld die reduksie van die vry fenol, sou die geredelik beskikbare A-tipe proantosianidien uit Arachis hypogea L., (+ )-epikatesjien-(2α - 7; 4α - 8)-(+)-katesjien verkieslik as fenoliese metieleter aan die reduktiewe reaksiekondisies blootgestel word. Metilering met diasometaan lewer gevolglik 'n mengsel van die heksametiel- en heptametieleterderivate. Die beperkte toeganklikheid van diasometaan by 5-0H(A) kan aan die waterstofbinding tussen die betrokke hidroksisubstituent en O-1(F-ring) toegeskryf word. Blootstelling van die heptametieleter van (+)-epikatesjien-(2α - 7; 4α - 8)-(+)- katesjien aan diisobutielaluminiumhidried (DIBAL) lewer twee produkte wat as gevolg van splyting van aromatiese metieleterbindings op die 4-posisie van die B- en E-ringe onderskeidelik, ontstaan. Die benutting van natriumsianobóorhidried in trifluoroasynsuur (NaBH3CNj CF3COOH) het egter tot die suksesvolle bepaling van die stereochemie van die terminale eenheid in die A-tipe proantosianidien gelei. Die reeks produkte wat via piraanring- en interflavanielbindingsplyting ontstaan, kan meganisties verklaar word in terme van die suurgekataliseerde vorming van 'n karbokatioon wat herrangskikking na 'n intermediere kinoonmetied ondergaan. Nukleofiele aanval van die hidriedioon lewer die tetrahidropirano[2,3-h]chromene en brokstukke afkomstig vanaf beide die 'boonste' en 'terminale' eenhede. Bevestiging vir die voorgestelde meganisme volg uit die reaksie van die heptametieleterderivaat van die A-tipe proantosianidien met CF3COOH. In die afwesigheid van 'n hidrieddonor word slegs klein hoeveelhede (+)-katesjien, geëpimeriseerde uitgangstof en hoofsaaklik polimeriese materiaal verkry. Die voorkoms van die reeks C-ring gei"someriseerde verbindings in nywerheidsgedroogde A. mearnsii-bas, dra waarskynlik by tot die kommersiële sukses van wattelbasekstrak. Die 'vrystelling' van 'n nukleofiele resorsinolring in flobatanniene verhoog waarskynlik die reaktiwiteit teenoor formaldeheid en dra aldus by tot die suksesvolle benutting van wattelbasekstrak in die koudsettende kleefstofbedryf. Die relatief planere sentrale CDF trisikliese sisteme in die dimeriese en CDFI tetrasikliese sisteme in trimeriese C-ring geïsomeriseerde verbindings, behoort verder tot verhoogde affiniteit vir kollageensubstrate by te dra en verklaar waarskynlik die uitgebreide benutting van wattelbasekstrak in die leerlooibedryf.
Open Access
Struktuur en sintese van metaboliete uit rooibostee (Aspalathus linearis): fisiologiese aktiwiteit en biomimetiese model vir die fermentasieproses
(University of the Free State, 1995) Marais, Charlene; Steenkamp, J. A.; Ferreira, D.
In die huidige ondersoek is nie alleen op die isolasie en karakterisering van wateroplosbare metaboliete uit rooibostee gefokus nie, maar is daar gepoog om 'n profiel van die fisiologiese aktiwiteit van sodanige verbindings daar te stel ten einde wetenskaplike stukrag te verleen aan aansprake oor die heilsame invloed van rooibostee wat reeds oor dekades heen gemaak word.
Open Access
Electrochemical, kinetic and molecular mechanic aspects of Rhodium(I) and Rhodium(II) complexes
(University of the Free State, 1998-11) Lamprecht, Delanie; Lamprecht, G. J.
English: Four Rh(I)(β-diketonato)(CO)(PPh3) complexes, in which the β-diketone has different electronegativities and steric hindrances, were successfully synthesised and characterised by means of Infrared and NMR spectroscopy. The crystal structure of (1 ,3-Diphenyl-1 ,3-propanedionato-KO, KO) Triphenyl Phosphine Rhodium(I) showed that the asymmetric unit consists of two centrosymmetric pair, but not a crystallographic inversion centre. The partial overlapping of the chelate ring of the one molecule with the phenyl ring of the other molecule can be attributed to π-π interactions between atoms of the two molecules. The oxidative addition kinetics of CH31to Rh(I)(β-diketonato)(CO)(PPh3) complexes was studied in the Visible, Infrared and NMR regions. The proposed oxidative addition mechanism of CH31 to Rh(I)(β-diketonato)( CO)(PPh3) complexes is a nucleophilic attack by the Rhodium atom on the Carbon atom of the methyl iodide, where a linear or a three-centred polar transition state is formed which leads to trans and cis addition respectively. The main purpose of the development of a Rh(I) Carbonyl Phosphine force field was not only to predict the molecular structure of Rh(I) complexes, but also to compute a possible transition states during the oxidative addition of CH31 to Rh(I)(β-diketonato)( CO)(PPh3) complexes. Steric energy calculations indicated that the oxidative addition of CH31to the Rh(I) Carbonyl Phosphine complexes would rather occur via a SN2 mechanism than a concerted three-centred mechanism. The negative entropy of activation and the negative experimental volume of activation obtained during oxidative addition of CH31 to Rh(I)(β-diketonato)( CO)(PPh3) complexes pointed towards an associative mechanism. An increase in solvent polarity leads to an increase in the second order rate constant. These results are indicative of a mechanism where a polar transition state is formed. During the electrochemical oxidation of Rh(I)(β-diketonato)(CO)(PPh3) the only possible co-ordination ligand was the solvent, CH3CN. The addition of solvents with different donosities revealed the co-ordination of the solvents during electrochemical oxidation. The addition of solvents with higher donosities and therefore better coordinating properties made it more difficult to reduce the Rh(III) species formed, back to Rh(I). The two electron irreversible electrochemical oxidation of Rh(I) to Rh(III) was confirmed during bulk electrolysis and Cyclic Voltammetric studies, where the addition of [BzN(Ethtcr to the solution stabilised the formation of Rh(III). The electronic effect of the substituents on the β-diketones showed that the reaction rate increases with the increase of the pKa-values of the freeβ-diketones. The effect of more electronegative substituents on the reactivity of the Rh(I) centre is explained by the fact that electron density is removed from the Rhodium metal, making the complex a stronger Lewis acid and less reactive towards oxidative addition. Steric effects were also perceptible in the present study where the β-diketones, btfa and tfaa, had the same pKa-values. The reaction rate of the bulkier btfa was slower than that of tfaa. Electrochemical oxidation justified the electronic effect, with the exception that steric parameters had no effect during electrochemical oxidation. The oxidation potentials of Rh(btfa)(CO)(PPh3) and Rh(tfaa)(CO)(PPh3), which have the same pKa-values, are the same, within experimental error. The technique of electrochemical oxidation can therefore be used to quantify steric effects during chemical oxidation. The final isomer formed during oxidative addition of CH31 to Rh(I)(β-diketonato)( CO)(PPh3) complexes depends on the nature and nucleophilicity of the ligands. A linear transition state leads to trans addition of CH31, and isomerisation forms a cis Rh(III) Carbonyl Phosphine isomer in the case of Rh(dbm)(CO)(PPh3) and Rh(ba)(CO)(PPh3) as final product. From IR spectroscopy it is clear that the final oxidative addition product of Rh(btfa)(CO)(PPh3) and Rh(tfaa)(CO)(PPh3) is the Rh(III) acyl complex.
Open Access
Chemical kinetics, electrochemistry and structural aspects of ferrocene-containing b-diketonato complexes of rhodium(I) and iridium(I)
(University of the Free State, 1999) Conradie, Jeanet
English: Synthetic routes to prepare new Rh(I)-β-diketonate complexes [Rh(FcCOCHCOR)(CO)2] and [Rh(FcCOCHCOR)(CO)(PPh3)] with Fc = ferrocenyl and R = Fc, C6H5, CH3 and CF3 have been developed and optimized. Optimized synthetic routes to iridium(I) complexes, [Ir(R'COCHCOR)(cod)], with R' = Fc and R = C6H5, CH3 and CF3, or with R' = CF3 and R = CH2CH3, CH(CH3)2 and C(CH3)3 have also been developed. 1H and 31P NMR studies indicated that for complexes of the type [Rh(β-diketonato)(CO)(PPh3)] with an unsymmetrical β-diketonato ligand, at least two main isomers exist in solution. The structure of one isomer of [Rh(fctfa)(CO)(PPh3)], as well as crystal structures of FcCOCH2COCF3, [Rh(fctfa)(CO)2] and [Rh(fctfa)(CO)(PPh3)(CH3)(I)] were solved. The chemical kinetics of the oxidative addition of iodomethane to [Rh(FcCOCHCOR)(CO)(PPh3)] has been studied utilizing IR, UV/visible, 1H NMR and 31P NMR techniques. The NMR studies revealed that the rate of oxidative addition of iodomethane to the different [Rh(FcCOCHCOR)(CO)(PPh3)] isomers was the same. A complete general reaction sequence for the oxidative addition of iodomethane to all [Rh(bidentate ligand)(CO)(PPh3)] complexes is: First set of reactionsSecond set of reactionsThird set of reactions{[Rh(III)-alkyl1] [Rh(III)-acyl1] }K2=k2/k-2Rh(I)+ CH3I k1k-1k3k-3k4k-4[Rh(III)-alkyl2][Rh(III)-acyl2] 1H and 31P NMR studies further showed that all rhodium-containing complexes in the above mentioned reaction scheme, are actually composed of at least two main isomers, that is Rh(I)A the rate of substitution becomes faster when the group electronegativity of the R groups increases. This tendency is, as expected, exactly the opposite to what was observed during oxidative addition. A general reaction mechanism for both Rh and Ir complexes was presented. An additional study on the rate of the β-diketonato substitution with 1,10-phenanthroline in complexes of the type [Ir(CF3COCHCOR)(cod)] with R = CH3, CH2CH3, CH(CH3)2 and C(CH3)3 showed that the size of R does not hamper the rate of substitution. All substitution reactions were independent of a solvent step. The cyclic voltammetry study of all the ferrocene-containing β-diketonato complexes of rhodium(I) and iridium(I) synthesized, exhibited a single electrochemically reversible redox couple corresponding to the formal reduction potential of the ferrocenyl group of the β-diketonato ligand coordinated to the rhodium or iridium complexes, as well as an electrochemically irreversible anodic oxidation peak which corresponds to the oxidation of the metal = Rh or Ir. The 31P NMR study on different six-membered chelate complexes, [Rh(L,L'-BID)(CO)(PPh3)], and related Rh(III) complexes, indicated a general decrease in coupling constants 1J(31P-103Rh) as the Rh-P bond length, determined by X-ray crystallography, increases according to the relationship d(Rh-P) = -0.0014(1) x 1J(31P-103Rh) + 2.49(2). The Rh-P bond lengths, d(Rh-P), varied between 2.23 Å and 2.36 Å. The electron density on the Rh(I) and Ir(I) metal centres was manipulated over a wide range by changing the R group on the coordinated ligand (FcCOCHCOR)- from the highly electron donating Fc group (χFc = 1.87) to C6H5, (χC6H5 = 2.21) to CH3(χCH3 = 2.34) to the strongly electron withdrawing CF3 group (χCF3 = 3.01). The effect of the different R groups on the β-diketonato ligand (FcCOCHCOR)- coordinated to the rhodium(I) and iridium(I) complexes was not only observed in kinetic rate constants, but also in formal reduction potentials of the ferrocenyl group, the oxidation potential of Rh(I) or Ir(I), pKa-values, IR stretching frequencies, and crystallographic bond lengths.
Open Access
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.
Open Access
Synthesis of isoflavonoid-neoflavonoid oligomers
(University of the Free State, 1999-08) Rohwer, Mark Bernhard; Ferreira, Daneel; Brandt, E. Vincent
English:A recent phytochemical study on the heartwood of the Purplewood Dalbergia (Dalbergianitidula) in our laboratories led to the isolation of the first pterocarpan-neoflavonoid dimers, Daljanelins A-C, and an isoflavan-neoflavonoid dimer, Daljanelin D. Although the structure of Daljanelin C has been confirmed by synthesis previously, synthetic evidence regarding the exact structures of Daljanelins A, Band D was still pending. This dissertation outlines the total syntheses of Daljanelins Band D, as well as the preparation of a suitable precursor to Daljanelin A. The crucial step in the retrosynthesis of Daljanelin B is the nucleophilic coupling of a suitably functionalized pterocarpan precursor with a benzofuranone. The electrophilic methylene bridge required at C-4 of (6aS, llaS)-medicarpin was introduced via 3-0-allylation, Claisen rearrangement, isomerization and oxidative cleavage of the olefin, benzylic reduction and in situ bromination, affording (6aS, llaS)-4-bromomethylmedicarpin. The requisite benzofuranone synthon was synthesized from vanillin by Dakin oxidation, Houben-Hoesch acylation, cyclization, protection of the hydroxy group and conversion to the tert-butyldimethylsilyl enol ether. The subsequent coupling of the pterocarpanoid and benzofuranoid fragments was achieved by means of desilylation of the latter with a strongly siliconophilic fluoride source. Grignard reaction of the resulting dimer with phenyl magnesium bromide and subsequent acid catalyzed dehydration and deprotection then afforded synthetic Daljanelin B, which exhibited the same IH NMR and CD properties as the natural product. Reductive cleavage of the pterocarpan C-ring in Daljanelin B afforded Daljanelin D, identical to the natural compound. It should be noted that the standard method for benzylic ether cleavage, i.e. hydrogenolysis on Pd(O) catalysts, was ineffectual. Good results were obtained, however, with a Na(CN)BHr TFA system. A suitable precursor to Daljanelin A, i.e. a 2-ethoxycarbonyl-substituted medicarpin, was synthesized from (6aS, llaS)-medicarpin via 2,8-dibromination, 3-0-methoxymethylation, selective lithium-bromine exchange and carboxylation at C-2, followed by 8-debromination. Reduction of the resulting ethyl benzoate, in situ bromination, benzylic coupling to a benzofuranoid, Grignard reaction and phenolic deprotection, as used in the synthesis of Daljanelin B, should prove instrumental in affording the desired dimer. Over and above structural elucidation, this research project has led to the following significant results: o The introduction of a hydroxy methyl group to position 4 of the pterocarpan skeleton constitutes an unusual accomplishment, since substitution on resorcinol-type pterocarpan A-rings is usually hampered by low aromatic nucleophilicity, as well as sensitivity of the C-ring towards the typically employed Bronsted and/or Lewis acids. o Electrophilic aromatic substitution on such A-rings, if observed at all, takes place in low yields at position 2. An analogue situation is encountered in natural and synthetic 5-deoxyflavonoids, where A-ring substitution is found exclusively at position 6. It is thus hoped that the protocol developed for the synthesis of Daljanelin B will alleviate these difficulties. o Although the yields In the bromination-carboxylation-debromination protocol towards Daljanelin A are still low, an alternative route for C-2-alkylation ofpterocarpans has been established. The novel synthetic routes towards Daljanelins A and B may thus collaborate in circumventing some of the problems typically associated with flavonoid and isoflavonoid A-ring functionalization.
Open Access
Direct synthesis of pterocarpans via aldol condensation
(University of the Free State, 2000-05) Van Aardt, Theunis G.; Van Rensburg, H.; Ferreira, D.
English: Pterocarpans, representing the second largest group of natural isoflavonoids, have received considerable interest on account of their medicinal properties over the last few years. These phytoalexins not only serve as antitoxins but also display antifungal, antiviral and antibacterial properties. Despite this, the study of these metabolites are restricted by their limited availability from natural sources. Furthermore, synthetic protocols allowing ready access to these compounds are restricted by the lack of availability of suitable starting materials and the potential introduction of stereoselectivity. Owing to the demand for enantiopure pterocarpans a direct stereoselective synthetic approach, based on the aldol condensation between appropriate phenylacetates and benzaldehydes, was developed. 2-Hydroxybenzaldehydes, protected as 2-0-methoxymethyl ethers, and 2- hydroxyphenylacetates, protected as TBDMS ethers, were subjected to aldol condensation employing lithium diisopropylamide, to afford the 2,3-diphenyl-3- hydroxypropanoates (40-76%, de = 22-100%). Subsequent reduction (LiAIH4), followed by Lewis acid (SnCI4, BnSH) deprotection of the 2'-O-MOM ethers, yielded the 3- benzylsulfanyl-2,3-diphenylpropanols (29-56%). Improved yields of these propanols were obtained by simply reversing the order of reactions (54-81%). B-ring formation using Mitsunobu conditions (TPP-DEAD) afforded the isoflavan silyl ethers in good yields (80-97%). The 2'-O-TBDMS derivatives were smoothly deprotected (TBAF) to yield the 2'-hydroxyisoflavans in excellent yields (96-99%). Finally, thiophilic Lewis acid (AgBF4, AgOTf or DMTSF) cyclisation produced the cis-pterocarpans in moderate to good yields (39-82%). Initial C-ring cyclisation (AgBF4) of the methyl 3-benzylsulfanyl-2,3-di(2- hydroxyphenyl)propanoates, followed by reduction (LiAIH4) and Mitsunobu (TPPDEAD) B-ring formation, afforded for the first time a trans-pterocarpan in a moderate overall yield of 12%. In order to address the issue of stereo control, we first attempted to introduce stereoselectivity during the aldol condensation. Stereoselective aldolisation employing diisopropylethylamine and chiral boron triflates, was evaluated utilizing achiral dibutylborontriflate. This system, though capable of effecting aldolisation, was ineffective to incorporate a broad range of substrates. Secondly, we converted the methyl propanoates to chiral derivatives of imidazolidin-2-one, bornane-l0,2-sultam and (lR,2S)-p-tol-N-norephedrine. Steric shielding of the enolates generated from these derivatives, prevented aldol condensation. Thirdly, using (-)-sparteine as chiral base afforded achiral products. Finally, in an effort to employ stereoselective epoxidation, attempts were made to synthesize 2-propenoates. All attempts to introduce the double bond gave disappointing yields. Although our attempts to introduce chirality failed, several alternatives still needs to be investigated in future endeavours. We have thus developed a highly efficient synthesis of cis-pterocarpans and succeeded in modifying this protocol to the novel synthesis of Irans-pterocarpanoids. Also, this synthetic protocol was modified to permit the stereoselective synthesis of 6ahydroxypterocarpans in high overall yields. The ease with which these protocols accommodate highly oxygenated substrates, featured by most natural pterocarpans, should contribute substantially to assess the chemical and physiological characteristics that may promote application of this class of phenolics as pharmaceutical or agricultural chemicals.
Open Access
Fundamental aspects of selected rhoduim complexes in homogeneous catalytic acetic acid production.
(University of the Free State, 2000-11) Damoense, Llewellyn Joseph; Roodt, A.; Purcell, W.
English: The aim of this study was to determine the mechanism for the reaction between iodomethane and complexes of the type [Rh(N,O-BID)(CO)(XR3)]; N,O-BID = mono anionic bidentate ligands of the general formula: (i) dimethylaminovinylketone; dmavk (ii) methyltrifluoroaminovinylketone; tavk; X= As or P, R = phenyl and substituted phenyls, PPh3, AsPh3, P(p-CI-Ph)3 or P(p-OMe-Ph)3. Determination of the mechanism was achieved utilizing X-ray crystallography, reaction kinetics and 31p_NMR. [Rh(dmavk)(CO)(PPh3)] crystallizes in the orthorombic crystal system with space group Pca21 and final R value of 2.04 %. [Rh(dmavk)(CO)(AsPh3)] and [Rh(dmavk)(I)(CH3)(CO)(PPh3)] crystallize in the triclinic crystal system with space group PI. The final R value for each was 3.88 and 4.77 % respectively. [Rh(dmavk)(I)(COCH3)(PPh3)] crystallizes in the monoclinic crystal system with space group P21/c and a final R value of6.72. In the case of the mono carbonyl complexes, i.e., for [Rh(dmavk)(CO)(PPh3)] and [Rh(dmavk)(CO)(AsPh3)], the PIAs atom is trans to the nitrogen atom of the N,O-BID ligand. The Rh-As bond is significantly longer than the Rh-P bond ( 2.3834(6) and 2.2751(13) A respectively). The successful isolation and Xray crystallographic characterization of the starting complex, [Rh(dmavk)(CO)(PPh3)], and its oxidative addition products for the reaction between and iodomethane, i.e., [Rh(dmavk)(I)(CH3)(CO)(PPh3)] and [Rh(dmavk)(I)(COCH3)(pPh3)] was for the first oxidative addition products is also retained from the same configuration present in the starting complex. 31p_NMR studies showed that for the [Rh(L,L-BID)(CO)(PPh3)] complexes: L,L'-BID = O,O-BID: tfaa, trop, cupf, acac, tta; O,S-BID: pbtu, hpt, anmeth, sacac; N,S-BID: cacsm, hacsm; N,O-BID: dmavk, ox, pie a fair correlation between 1J(PRh) and the Rh-P bond distance exists In these complexes; a decrease in Rh-P bond distance results In an increase in IJ(PRh). The [Rh(N,O-BID)(CO)(XR3)] complexes undergo oxidative addition by iodomethane, forming the Rh(III)-alkyl species via an equilibrium step, followed by the formation of the Rh(lII)-acyl species according to the following reaction: A significant solvent effect was observed for the oxidative addition reaction between iodomethane and [Rh(dmavk)(CO)(PPh3)]. At 25°C, this reaction proceeds 8 times faster in the highly polar solvent acetonitrile (k, = 89(6)xl02 M"IS"I)compared to the least polar solvent chloroform (k, = 11.4(4)xl02 M"IS"I). The activation parameters (L1H# and L1S#) were determined from the temperature dependence of k, in acetone. Large negative L1S# values (L1S# = -139(40) J KI mol") and typical L1H# values (L1H# = 35(4) kj mol") were obtained. Considering these experimental results, the formation of a linear, polar transition state with subsequent formation of an ion-pair intermediate is postulated. The rate constant of the oxidative addition was increased by both electronic and steric manipulation. The electronic manipulation was achieved by firstly the introduction of electron/donating substituents (CH3 in place ofCF3) on the bidentate ligand, resulting in a four fold increase in magnitude for the rate of oxidative addition; and secondly by the interchanging triphenyl phosphine and its derivatives [PPh3 vs. P(p-CI-Ph)3 vs. P(p-OMe- Ph)3]. The' formation rate of the Rh(III)-acyl species was found to be relative independent of the variation in nucleophilic character of the metal center. Steric manipulation was achieved by interchanging PPh3 with AsPh3. Replacing the PPh3 ligand by AsPh3 leads to an increase in the rate of oxidative addition and a decrease in the rate of reductive elimination, resulting in an increase in the equilibrium constant for this step. A significant (ca. one order of magnitude) decrease in CO-insertion was observed from PPh3 to AsPh3 (l2.0(6)xl0-4 compared to 1.32(2)xlO-4 sol). An increase in the K, values (i.e. thermodynamic stability of the Rh(III)-alkyl species) were observed by increasing the nucleophilic character on the Rh center and by decreasing the steric demand on the meta! center. The introduction of these N,O-BID ligands to the Rh(I) center in these complexes resulted in at least a ea. 4 fold activation in the oxidative addition rate as compared to the known O,O-BID ligand systems (i.e. acac, ox, etc.)
Open Access
Characterisation and substitution kinetics of hromium(III)- and obalt(III)nitrilotriacetato complexes
(University of the Free State, 2000-11) Visser, Hendrik Gideon; PurcelI, W.; Basson, S. S.
English: The synthesis and reactions of Co(llI) and Cr(lIl) complexes with nitrilotriacetic acid (nta) as tetradentate ligand have widespread interest, mainly because of the fact that these complexes can be usedas biological model complexes and because nta labilises usually inert metal centres. Mori et al (1958:940) and Uehara et al. (1967:2317) were the first to prepare different Co(III)-nta and Cr(III)-nta complexes respectively. Since then these complexes have been used in several kinetic and synthetic studies (Visser et al. 1997:2581; Visser et al. 1994:1051 and Thacker & Higginson, 1975:704). However the identity and purity of these complexes were questionable and had not been solved up to the time of this study. The question regarding the identity of the different Co(III)-nta species in solution at different pH levels have largely been accounted for in this study (refer to Scheme 1). Scheme 1 Complexes and reactions of Co(III)-nta. (Refer to PDF attached) The identity of the complex first prepared by Mori et al (1958:940) was finally characterised with X-ray crystallography as being [Co(nta)(1l-0H)]22-. Crystals of CS2[Co(nta)(J.l-OH)].4H20 crystallises in the orthorombic space group 141/a (R1= 0.0322). The Co-N bonding distance was determined as 1.922(6) A. [Co(nta)(J.l-OH)]}- undergo bridge-cleavage upon acidification with H+ ions to form [Co(nta)(H20)2]. The pKa of this reaction was determined as 3.09(3). Further acidification of [Co(nta)(H20)2] leads to the stepwise dissociation of nta. The formation of an ion associated species between [Co(nta)(H20)2] and H+ions upon addition of acid is postulated. This ion associated species dissociates in the rate determining step to form the tridentate nta complex, [Co(,,3-nta)(H20hr. The value of k1 at 25.9 °C was determined as 0.13(1) S-1. Another acid-base equilibrium is observed when the pH of a [Co(nta)(H20)2]solution is increased. It was concluded that the newly formed species is not the dimer, but rather [Co(nta)(H20)(OH)]" which reverts back to the dimer at pH 6 - 7 after several days. This second pKawas determined as 6.52(2). The substitution reactions between [Co(nta)(H20)2] and NCS- ions have been investigated, At pH = 2.00 NCS-ions substitute the aqua ligands in a stepwise fashion. The substitution of the first aqua ligand (k1= 2.4(1) x 10-2M-1 S-1at 24.7 °C) is about 120 orders of magnitude faster than the rate of substitution of the second aqua ligand (~ = 1.98(6) X 10-4M-1S-1at 24.7 °C). The [Co(nta)(H20)OHr complex reacts about 70 times faster at 24.7 "C with NCS- than [Co(nta)(H20)2] with NCS- (k2 = 1.68(5) M-1S-1vs. 2.4(1) x 10-2 M-1 S-1for k1 at 24.7 °C). This clearly indicates that the hydroxo ligand labinses the eis-aqua bond so that an increase in rate is observed. Hydroxide is not substituted by NCS- ions at higher pH so that only one reaction is observed spectrophotometrically. [Co(nta)(wOH)]i- undergo bridge cleavage at higher pH upon addition of various ligands like en, dmap or py. As a result of this several [Co(nta)(LL')] and [Co(nta)(L)2] (LL' = various N,N and N,O donors and L = dmap, py) complexes have been synthesised. The X-ray crystallographical structure determination of [Co(nta)(N,N-Et2en)] is a result of one of the synthetic studies. Crystals of [Co(nta)(N,N-Et2en)] crystallises in the orthorombic space group Pbcm (R1 = 0.0309). The Co-N bonding distance was determined as 1.950(4) A. The bridge cleavage reactions of u-hydroxo bridged Co(III)-complexes have not been studied to our knowledge. The substitution reactions between [Co(nta)(1l-0H)]l- and various ligands like dmap, py, en and N,N-Et2en have been investigated at pH 9 - 11.5. It is suggested that [Co(nta)(1l-0H)]/- equilibrates rapidly in aqueous basic solutions with a mono-u-hydroxo bridged species and that both these species react with the incoming ligand to form ion associated species (rapid) which dissociates in the rate determining step to the products. The existence of the formed mono-u-hydroxo bridged complex was confirmed by the fact that the value for the equilibrium constant, pKoH, was determined as 3.3 for all the reactions studied. This mono-u-hydroxo species is more labile towards substitution than the dimer itself as is illustrated by the fact that k1 < k2 for all the reactions studied. The values of k1 varied between 8.7(7) X 10-5 S-1 and 3.3(7) x 10-3 S-1 and those of k2 between 6.8(2) x 10-4S-1 and 5.7(2) x 10-2S-1. The synthesis and characterisation of Cs2[Co(nta)(C03)].H20 was also undertaken. This complex crystallises in the monoclinic space group P21/c (R1 = 0.0249) and can be used as an alternative to [Co(nta)(1l-0H)]l- for the synthesis of different Co(III)-nta complexes. The Co-N bonding distance was calculated as 1.920(2) A. The uncertainty surrounding the identity of the Cr(III)-nta complexes first prepared by Uehara et al. (1967:2317) have been erased with the X-ray crystal structure determination of Cs2[Cr(nta)(j.l-OH)].4H20. CS2[Cr(nta)(1l-0H)].4H20 crystallise in two different space groups, tetragonal 141/a (R1 = 0.0354) and monoclinic P21/c (R1 = 0.0354). The Cr-N bonding distances were 2.048(9) and 2.061 (3) A respectively. The strain experienced by the glycinato rings of coordinated nta decreases in the order G > R for all the complexes studied. The R rings in all the complexes are almost perfectly planar in all cases, while the G rings are non-planar.
Open Access
A new method to remove and recover contaminating sodium salts from industrial wastewater utilising polymer-bound crown ethers
(University of the Free State, 2001-11) Koortzen, Johannes Gerhardus; Swarts, J. C.
English: The aim of this study was to develop a new technique to clean the total factory generated wastewater as seen in the light of the background given in Chapter 1. It was decided to develop a material that would enable an industry to complex sodium cautions from a contaminated source, and to release the complexed sodium cautions, under controlled conditions, at a previously determined site, or receiving reservoir, in a cyclic manner. For this reason, 32 different functionalised crown ether derivatives were synthesised to produce a series of 17 new crown ether derivatives, including 4 carboxylic acid, 4 amide, 4 alcohol and 4 amine crown ether derivatives, with spacer ranging from one to four carbon atoms in the side chain that separate the functional group from the crown ether moiety. Selected crown ether functionalised derivatives was anchored on polymeric supports and their sodium caution complexation ability was determined. Twenty (20) polymeric carriers were also synthesised. These include the synthesis of 12 new water-soluble polyaspartamide derivatives as well as 5 new polyepichlorohydrin water-insoluble derivatives. The experimental procedures for the synthesis of the water-soluble polymers could be tuned to achieve exact ratios between polymer anchored crown ethers and several other polymer side chains containing functional groups. The carboxylic acid derivatives could be anchored to the water-soluble polymer and this reaction could be tuned to achieve 100 % coupling, with the use of the coupling reagent O-benzotriazolyl-N,N,N',N'- tetramethyluronium hexafluorophosphate. An elastomeric solid support was also synthesised by the curing of hydroxy terminated polybutadiene with isophorone diisocyanate. It was also demonstrated that crown ether derivatives and/or polymeric carriers could be anchored onto this elastomeric solid support, with or without the use of a spacer between the elastomeric solid support and the crown ether. Several new elastomeric solid supports containing crown ethers were synthesised. Complexation studies of Na+ dissolved in an aqueous phase by crown ether functionalised elastomeric solid supports were demonstrated, and it was found that 1.28 g Na+ I m2 surface area of the sodium caution scavenging device could be removed. Acid media was used to accomplish the release of the Na+ from this elastomeric solid support, and it was found that 0.65 g Na+ I m2 surface area of the sodium caution scavenging device could be released.
Open Access
Conformational analysis of oligomeric profisetinidins
(University of the Free State, 2007-02) Potgieter, Eleonora Deborah; Ferreira, D.; Brandt, E. V.
English: The profisetinidins are an important class of condensed tannins, or proanthocyanidins. Historically, studies towards the structure and conformation of proanthocyanidins were done on their peracetate and permethyl acetate derivatives. A current upsurge in industrial and biological applications of proanthocyanidins has prompted the present efforts at detailed analysis of the conformational behaviour of the naturally occurring free phenolic oligomeric profisetinidins. Studies towards the structure and conformational analysis of a small number of free phenolic dimeric procyanidins that are 4→8 coupled and only one free phenolic dimeric profisetinidin, fisetinidol-(4α→8)-catechin, have hitherto been reported. This study centres on the use of 1H, 13C, gradient COSY, COSY 45, COSY 90W, NOESY PH and HMQC NMR experiments in different solvents and at different temperatures to assign the hydrogen and some carbon resonances of the free phenolic profisetinidins that are found in commercially important southern hemisphere trees, namely Black Wattle (Acacia mearnsii) and Quebracho (Schinopsis balansae). These results, together with data obtained from CD spectra in methanol, were then used to study the conformations of these compounds. Dimers with 2,3-trans-3,4-trans (2,4-cis) configuration, namely fisetinidol-(4α→8)-catechin, fisetinidol-(4α→6)-catechin, ent-fisetinidol-(4β→8)-catechin and ent-fisetinidol-(4β→6)- catechin all displayed sets of duplicate resonances on 1H NMR spectra, indicating the presence of rotamers on an NMR time-scale at ambient temperatures. The proton resonances of the rotamers of the 4→6 linked dimers displayed insignificant chemical shift differences due to the similar magnetic environments and linear shape of both rotamers. The proton resonances of the rotamers of the 4→8 linked dimers displayed significant chemical shift differences due to the presence of compact and extended rotamers resulting in large changes in magnetic environment due to anisotropic effects. The type of solvent, temperature as well as the relative presence of water or cadmium nitrate had a strong influence on the relative concentrations of the rotamers, the conformations of the heterocyclic C- and F-rings as well as the visibility of hydroxy groups. The F-rings all displayed A/E- conformational exchange with line shapes indicating possible skewed boat conformations in some instances. The C-ring conformations ranged from rings with A/E conformational exchange to preferred E-conformers. The dimers with 2,3-trans-3,4-cis (2,4-trans) configuration, namely fisetinidol-(4β→8)- catechin, fisetinidol-(4β→6)-catechin and ent-fisetinidol-(4α→8)-catechin displayed only one set of resonances on 1H NMR spectra at ambient temperatures. The presence of intramolecular hydrogen bonding and limited conformational exchange was confirmed by the following observations: a) Selective broadening of proton resonances in both the heterocyclic and aromatic regions of 1D NMR spectra. b) Sharpening of resonances in 1D spectra at elevated temperatures. c) The presence of abundant coupling between heterocyclic and aromatic ring protons as observed on 2D spectra. d) Coupling between 2-HC and 4-HC on 2D NMR spectra. The C-rings had preferred A-conformations, with the F-rings displaying A/E conformational exchange with line shapes indicating possible skewed boat conformations in some instances. 2D NMR experiments afforded estimations, in some cases, of the angles between the plane of the B-ring and the 2-CC→2-HC bond, the plane of the D-ring and the 4-CF→4-HF bond as well as the plane of the D-ring and the 4-CC→4-HC. The resonances of 4-CC of the 2,3-trans-3,4-trans dimers displayed significant chemical shift differences (± 41 ppm) compared to 4-CC of the 2,3-trans-3,4-cis dimers (± 31 ppm).This could serve as a possible indicator of the relative configurations of the C-rings of 2,3-trans profisetinidins dimers. CD studies of al seven abovementioned dimers, as well as four trimers from Acacia mearnsii displayed complex curves with a number of strong Cotton effects. Although some trends were observed, it was abundantly evident that the chiroptical characteristics of this class of compounds are too complex to be interpreted in terms of the empirical quadrant rule.
Open Access
Coordination chemistry and solution behaviour of gold (I) complexes
(University of the Free State, 2007-11) Sam, Zolisa Agnes; Roodt, A.
English: The aim of this study was to extend the knowledge base of gold(I) coordination chemistry and investigate the substitution behaviour of these complexes with sulphurdonor ligands. The water-soluble and air-stable ligand 1,3,5-triaza-7- phosphatricyclo[3.3.1.13,7]decane (PTA) with low steric demand was employed in the synthesis of the various complexes in this study. The [Au(PTA)Cl] complex was reacted with S-donor ligands such as SCN¯, thiourea and methyl thiourea and the equilibrium constant determination was done using 31P NMR by monitoring the chemical shift change when stoichiometric amounts of the ligand are added to the [Au(PTA)Cl] solution. The equilibrium constants obtained were 0.070(6), 4.191(1) and 6.734(3) for SCN¯, thiourea and methyl thiourea as entering ligands, respectively. The X-ray crystal structure of the inclusion of the PTA ‘guest’ molecule into the ‘host’ b- cyclodextrin (b-CD) was determined. The PTA-b-CD·8H2O inclusion compound crystallises in the monoclinic space group P21 with eight solvent water molecules in an asymmetric unit and was refined to a final R value of 4.35%. The packing within the PTA-b-CD·8H2O inclusion compound is of a ‘herring-bone’ type motif. An attempt to include auranofin {[Au(PEt3)(Sgluc)]; Sgluc = thioglucose} into the cavity of the b- cyclodextrin resulted in only auranofin crystallising without being included. However, since the data collection for the auranofin compound was done at 100 K, careful observations in parameters such as selected torsion and bond angles were noted to have 1-4° changes as compared to the known auranofin structure investigated at room temperature, which clearly indicated a phase change and a new polymorph at 100 K. The pure auranofin compound investigated in this study crystallises in the monoclinic space group P21 and was refined to a final R value of 1.59%. Further study of the interactions of b-cyclodextrin with PTA and related ligands and gold(I) complexes in this study was investigated with NMR spectroscopy. This was done by the determination of the equilibrium constant when these complexes are included into the b-cyclodextrin. The equilibrium constants calculated for PTA, (PTAMe)+ and PPh3 were 8.7(1) x 102 and 23(4) and 10(6) M-1, respectively, while for the [Au(PTAMe)Cl] and [Au(dppe)2]Cl equilibrium constants of 23(5) and 6(1) M-1 were obtained. The PTA ligand clearly showed the largest ‘host-guest’ stability. The solubility of the phenyl compounds, following the inclusion, was not improved that much as compared to the PTA compounds which may be due to steric hindrance and orientation of the phenyl groups being too large to be incorporated into the b-cyclodextrin. This phenomenon is also noted in the unsuccessful incorporation of auranofin which may be due the orientation of the ethyl groups into b-cyclodextrin. In an attempt to increase the solubility of these gold(I) complexes, bidentate P-donor ligand systems with a bridging ferrocene group, functionalised by hydrophilic moieties, were synthesised. These complexes were unambiguously characterised by X-ray crystallography. The following dinuclear gold(I) crystal structures are reported, with their general crystal data reported in parenthesis: [(AuCl)2(m-dppf-CH(CH3)N(CH3)2)] (Monoclinic, P21/n, R = 4.94%) [(AuSCN)2(m-dppf-CH(CH3)N(CH3)2)] (Triclinic, P 1 , R = 5.76%) [(AuCl)2(m-dppf-CH(CH3)OAc)] (Orthorhombic, Pbca, R = 4.09%) [(AuSCN)2(m-dppf-CH(CH3)OAc)] (Triclinic, P 1 , R = 4.36%) [(AuSCN)2(m-dppf)] (Monoclinic, C2/c, R = 2.36%) The SCN¯ ligand in the thiocyanato gold(I) dppf structures coordinated to the soft Au(I) metal centre via the softer S atom. An interesting factor was the isomorphism identified for the two [(AuSCN)2(m-dppf-CH(CH3)N(CH3)2)] and [(AuSCN)2(m-dppf-CH(CH3)OAc)] structures while the structure for the [(AuSCN)2(m-dppf)] compound was interlinked by short Au…Au contacts of 2.9798(7) Å of which none were observed for the other structures. Auranofin and its derivative compounds such as PTA-auranofin, PTAMe-auranofin and triethylarsine-auranofin were utilised and tested for biological activity against cancer cell lines. Furthermore, a preliminary chemiluminescence assay was done with the compounds at three different concentrations (0.3, 3.1 and 12.5 mM for each compound) to determine their effect on the chemiluminescence of isolated blood neutrophils. The auranofin compound was included in the investigations as reference. The A2780 human ovarian cancer cell lines are the most sensitive to all derivatives while the arsine-auranofin compound showed good activity against A2780 human ovarian cancer cell lines with an IC50 of only about 0.0076 mg/mL. Generally, auranofin and arsineauranofin gave results closely related to each other with arsine-auranofin having higher toxicity to other cells whereas PTA-auranofin and PTAMe-auranofin showed more correlation to each other and had less activity. For the preliminary chemiluminescence assays it can be mentioned that for all auranofin derivatives, at low concentrations the compounds act as stimulants to the neutrophil chemiluminescence activity and at higher concentrations the compounds act as inhibitors to neutrophil activity. Complex substitution behaviour was observed for selected gold(I) dinuclear {[(AuCl)2(m- dppf-CH(CH3)OAc)]} and mononuclear systems {[Au(PX)Cl]; X = Ph3 or Ph2Fc} when the chloride is substituted with ligands such as L-cysteine and SCN¯ as studied by UVVis and 31P NMR. Furthermore, fast reaction kinetics for the chloride substitution with ligands such as SCN¯ and dimethylthiourea from the mononuclear [Au(PPh3)Cl] complex was investigated with stopped-flow techniques. The overall rate constants for the substitutions from [Au(PPh3)Cl] with SCN¯ and dimethyl thiourea representing the forward reactions were obtained as k1 = 13(1) and 2.17(1) x 103 M-1s-1 respectively. Thus, it was concluded that chloride substitution reactions on linear gold(I) systems are extremely fast reactions.