dc.contributor.advisor | Yngve H. Stenstrøm | |
dc.contributor.advisor | Trond Vidar Hansen | |
dc.contributor.advisor | Simen Antonsen | |
dc.contributor.author | Bentzen, Maria | |
dc.date.accessioned | 2023-11-30T17:27:09Z | |
dc.date.available | 2023-11-30T17:27:09Z | |
dc.date.issued | 2023 | |
dc.identifier | no.nmbu:wiseflow:6970730:56568286 | |
dc.identifier.uri | https://hdl.handle.net/11250/3105493 | |
dc.description.abstract | Karbazol-alkaloider er en gruppe naturstoffer kjent for sine spennende biologiske aktiviteter.
Karbazol-alkaloidet Clausenalansine A ble isolert fra frukten til Clausena lansium og har vist
nevrobeskyttende aktivitet mot Parkinsons sykdom. Clausenalansine A og dens analoger er
derfor verdifulle ressurser i søken etter nye behandlinger for nevrodegenerative sykdommer. I
denne oppgaven ble mellomprodukter mot Clausenalansine A syntetisert.
Utgangsmaterialet var 3-aminofenol og 4-bromanisol. 3-Aminofenol ble beskyttet med tbutyldifenylsilyl. Produktet av denne reaksjonen var 3-((t-butyldifenylsilyl)oksy)anilin med et
utbytte på 77%.
Produktet reagerte med 4-bromanisol i en Buchwald-Hartwig aminering. Produktet av denne
reaksjonen var 3-((t-butyldifenylsilyl)oksy)-N-(4-metoksyfenyl)anilin med et utbytte på 30%.
En oksidativ krysskoblingsreaksjon ble forsøkt for å danne karbazol-enheten. Dette resulterte
i produktet 2-((t-butyldifenylsilyl)oksy)-6-metoksy-9H-karbazol. Karbazolet ble avbeskyttet,
og 6-metoksy-9H-karbazol-2-ol ble syntetisert med et utbytte på 5% over to trinn.
Det var interessant i dette prosjektet å utforske en orto-formylering på et karbazol-derivat.
Grunnet lavt utbytte ble reaksjonen utført på N(4-metoksifenyl)-3-aminofenol, som ble
syntetisert fra 3-((t-butyldifenylsilyl)oksy)-N-(4-metoksyfenyl)anilin med et utbytte på 81%.
Orto-formylering ga ikke ønsket produkt.
En ny syntesevei til Clausenalansine A ble utforsket med 3-brom-4-nitroanisol og 4-
hydroksyfenylborsyre som utgangsmaterialer. En Suzuki-kobling ble utført på 4-brom-3-
nitroanisol og 4-hydroksyfenylborsyre, og 2-nitro-4-metoksy-4'-hydroksybifenyl ble isolert
med kvantitativt utbytte. Det ble forsøkt å danne karbazol-enheten med en reduktiv
sykliseringsreaksjon. Dette var ikke vellykket, og det ønskede produktet ble ikke observert. | |
dc.description.abstract | Carbazole alkaloids are a group of natural products known for their exciting biological
activities. The carbazole alkaloid Clausenalansine A was isolated from the fruits of Clausena
lansium and was found to have neuroprotective activity against Parkinson’s disease.
Clausenalansine A and its analogues are valuable resources in the search for new treatments
for neurodegenerative diseases. In this thesis, intermediates towards Clausenalansine A were
prepared.
The starting material was 3-aminophenol and 4-bromoanisole. 3-aminophenol was protected
with TBDPS. The product of this reaction was 3-((t-butyldiphenylsilyl)oxy)aniline in a yield
of 77%.
The product reacted with 4-bromoanisole in a Buchwald-Hartwig amination. The product of
this reaction was 3-((t-butyldiphenylsilyl)oxy)-N-(4-methoxyphenyl)aniline in a yield of 30%.
An oxidative cross-coupling reaction was performed to form the carbazole moiety. This led to
the product 2-((t-butyldiphenylsilyl)oxy)-6-methoxy-9H-carbazole. The carbazole product
was deprotected, and 6-methoxy-9H-carbazole-2-ol was synthesised with a yield of 5% over
two steps.
It was interesting in this project to explore the ortho-formylation reaction on a carbazole
product. Due to low yields, it was instead performed on N(4-methoxyphenyl)-3-aminophenol,
which was synthesized from 3-((t-butyldiphenylsilyl)oxy)-N-(4-methoxyphenyl)aniline with a
yield of 81%. The ortho-formylation did not yield the desired product.
A new synthesis path to Clausenalansine A was explored with 3-bromo-4-nitroanisole and 4-
hydroxyphenylboronic acid as starting materials. A Suzuki coupling was performed on 4-
bromo-3-nitroanisole and 4-hydroxyphenylboronic, and 2-nitro-4-methoxy-4’-
hydroxybiphenyl was isolated with a quantitative yield. A reductive cyclization reaction was
performed to form the carbazole moiety. This was not successful, and the desired product was
not observed. | |
dc.language | eng | |
dc.publisher | Norwegian University of Life Sciences | |
dc.title | Studies of Cyclization Reactions for the Formation of Carbazole Alkaloids | |
dc.type | Master thesis | |