Thesis (PhD)--Stellenbosch University, 2000. / ENGLISH ABSTRACT: The aim of this thesis is to use tin-mediated reactions to differentiate between the four
zones in the myo-inositol ring that consists of five contiguous equatorial and one axial
hydroxyl groups. It is expected to give chemical control over the hexitol that can be
put to good use in commercializing the phosphate derivatives of myo-inositol that are
of pharmaceutical value.
As point of departure 1,2-0-cyclohexylidene-myo-inositol (II.I) was synthesized that
contains a tetrol with one end adjacent to an axial acetal oxygen and the other end
adjacent to an equatorial acetal oxygen. The selective protection of position 3 (Dmyo-
inositol) was investigated. Various problems lead to the selective silylation of
the acetal at position 5. The silane forms the basis of the subsequent investigation
because the cyclitol is now divided into an isolated mono-ol and a trans-diol allowing
for easier differentiation between the various hydroxyl groups.
It was indeed possible to differentiate the trans-diol from the mono-ol by using
carbonylation and allylidenation. Ring closure occurs in both cases. In the
carbonylation case the resultant five-membered ring is less stable than that of the
allylidene due to the Sp² hybridized carbon atom of the carbonate compared to theSp³
hybridized carbon of the allylidene group.
Preliminary work was done on the racerrue 1,2-0-cyclohexylidene-myo-inositol
(II.VII) in order to use the acquired technology on the chiral camphor analog. The
transition from racemic to chiral proved problematic since the camphor acetal is
difficult to prepare and its selective silylation differs from that observed for
cyc1ohexylidene. The camphor acetal itself was silylated in the process.
(S)-( -)-Camphanic chloride was therefore used as chiral auxiliary in the protection of
position six of the racemic 1,2,3,4,5-protected myo-inositol, thus solving the problems
encountered in the protection of position six whilst combining the protection and
chiral induction steps. The resultant diastereomers could both be used in the synthesis
of IP₃ and IP₄ respectively, eliminating the disposal of half ofthe product. This project lead to the development of useful chiral differentially protected myoinositol
derivatives, which could be useful in synthesis of various other myo-inositol
derivatives.
Besides the synthesis of useful chiral differentially protected myo-inositol derivatives,
this investigation developed new applications in the tin-mediated derivatization of
sugars.
The following compounds were synthesized during this investigation. Bold numbers
indicates novel compounds. / AFRIKAANSE OPSOMMING: Die doel van hierdie proefskrif is om met behulp van tin-bemiddelde reaksies
onderskeid te maak tussen die vier sones in die mia-inositolring, wat bestaan uit vyf
aaneenlopende ekwatoriale hidroksigroepe en een aksiale hidroksigroep. Die
verwagting was om vinnig, effektiewe chemiese beheer oor die genoemde heksitol te
verkry om sodoende chemies en kommersiëel munt te slaan uit die farmaseutiese
werking van die fosfaatafgeleides van mia-inositol.
As eerste uitgangspunt is 1,2-0-sikloheksilideen-mia-inositol (II.I) berei, wat lei tot
die vorming van 'n tetrol waarvan die een punt naasliggend aan 'n aksiale
asetaalsuurstofatoom en die ander punt naasliggend aan 'n ekwatoriale asetaalsuurstof
is. As voortsetting is die selektiewe beskerming van posisie 3 (D-mia-inositol)
ondersoek. Velerlei probleme lei tot die selektiewe sililering van die asetaal by
posisie 5 (II.VII). Die silieleter vorm die basis van al die daaropvolgende ondersoeke
omdat dit die siklitol in 'n trans-diol en 'n geïsoleerde mono-ol verdeel en die
verskillende hidroksigroepe daarvan makliker van mekaar onderskei kan word.
Dit is inderdaad moontlik om die trans-diol van die mono-ol te onderskei deur
karbonilering of allilidenering. In albei gevalle vind ringannulering plaas. In die
geval van die karbonilering is die gevormde vyflidring minder stabiel as wat die geval
is vir die allilideengroep. Die rede hiervoor is dat die karbonaatkoolstofatoom Sp²-
gehibridiseer is terwyl die ooreenstemmende koolstofatoom van die allilideen Sp³-
gehibridiseer is.
Ontwikkelingswerk is op die rasemiese 1,2-0-sikloheksilideen-mia-inositol (II.VII)
gedoen ten einde dit op die chirale kamferasetaalanaloog toe te pas. Die oorgang van
rasemies na chiraal is egter problematies aangesien die kamferasetaal moeiliker vorm
en selfs as dit vorm toon die reaksies, soos byvoorbeeld die sililering, ander
selektiwiteit as wat die geval is vir die rasemiese mengsel. Sililering van die
kamferasetaallei tot sililering van die kamfer self.
(S)-(-)-kamfanoïelchloried is gevolglik as chirale hulpreagens gebruik om posisie 6
van die rasemiese 1,2,3,4,5-beskermde-mia-inositol te beskerm. Hierdie benadering los die problematiek rondom die beskerming van posisie 6 sowel as die induksie van
chiraliteit op. Die twee diastereomere wat op hierdie wyse vorm, kan albei in die
sintese van onderskeidelik IP₃ en IP₄ gebruik word, wat die verlies aan helfte van die
produk verhoed.
Behalwe die daarstelling van bruikbare chirale differensiëel-beskermde mioinositolafgeleides
wat gebruik kan word om 'n verskeidenheid chirale mioinositolafgeleides
te berei, het hierdie ondersoek nuwe toepassings in tin-bemiddelde
derivatisering van suikers daargestel.
Die volgende verbindings is gedurende die verloop van hierdie ondersoek
gesintetiseer, waar verbindings vir die eerste keer gesintetiseer is word dit aangedui
deur die verbinding se nommer vet (bold) te druk.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:sun/oai:scholar.sun.ac.za:10019.1/52035 |
| Date | 03 1900 |
| Creators | Prinsloo, Mare-Loe |
| Contributors | Bredenkamp, M. W., Stellenbosch University. Faculty of Science. Dept. of Chemistry & Polymer Science . |
| Publisher | Stellenbosch : Stellenbosch University |
| Source Sets | South African National ETD Portal |
| Language | af_ZA |
| Detected Language | Unknown |
| Type | Thesis |
| Format | 171 p. : ill. |
| Rights | Stellenbosch University |
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