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Synthetic studies on naphthoxylosides - labeled compounds and mechanistic studies on acetals

Johnsson, Richard LU (2008)
Abstract
Labeled analogs to an antiproliferative naphthoxyloside have been synthesized and evaluated. Our investigations have shown that the fluorescently labeled analogs are poor structural analogs, and the physical and biological properties are altered to a large extent. Instead, a radioactively labeled compound was synthesized, which made it possible to follow the pathway in the cell. The results showed a difference between a normal and a transformed cell line based on accumulation of the naphthoxyloside and it appears that the transformed cells process the naphthoxylosides faster than the normal cells do.



This work also involved mechanistic studies for regioselective openings of benzylidene acetals with boranes and a new... (More)
Labeled analogs to an antiproliferative naphthoxyloside have been synthesized and evaluated. Our investigations have shown that the fluorescently labeled analogs are poor structural analogs, and the physical and biological properties are altered to a large extent. Instead, a radioactively labeled compound was synthesized, which made it possible to follow the pathway in the cell. The results showed a difference between a normal and a transformed cell line based on accumulation of the naphthoxyloside and it appears that the transformed cells process the naphthoxylosides faster than the normal cells do.



This work also involved mechanistic studies for regioselective openings of benzylidene acetals with boranes and a new mechanism has been proposed. As it turns out, the regioselectivity can be controlled by the choice of borane, Lewis acid and solvent. When the borane is activated by a Lewis acid, the reaction rate is increased and the borane is the most electrophilic species, thus directing the regioselectivity. In contrary, when the borane is not activated, the Lewis acid is the most electrophilic species that directs the regioselectivity. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Universitetslektor Almqvist, Fredrik, Organic Chemistry, Umeå University
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Fluorescent xylosides, Carbohydrates, Naphthoxylosides, Cancer, Mechanistic studies, Radioactive xylosides, Acetals
pages
102 pages
publisher
Organic Chemistry, Lund University
defense location
Hörsal B; Kemicentrum, Getingevägen 60, Lunds Tekniska Högskola
defense date
2008-04-25 09:30:00
ISBN
978-91-628-7473-5
language
English
LU publication?
yes
additional info
Cancer är ett samlingsnamn på en rad sjukdomar som beror på okontrollerad celltillväxt. År 2005 orsakades omkring 13 % av alla dödsfall i världen av cancer. Det finns många olika typer av cancer och överlevnaden varierar mellan 1 % för cancer i bukspottskörteln till 99 % för vissa typer av hudcancer. Vi har arbetat med en kemisk substansklass som består av björksocker (xylos) kopplat till naftalen (samma ämne som i vissa malkulor) som hämmar cancertillväxten. Vad som gör att vissa av dessa ämnen, som vi kallar naftoxylosider, selektivt hämmar cancerceller är dock till stora delar ännu okänt. I detta arbete har vi försökt att ta reda på hur naftoxylosiderna rör sig i celler, för att förstå den tumörhämmande effekten. Vi har arbetat med föreningar som är märkta på olika vis. I våra första försök använde vi fluorescenta grupper, som gör det möjligt att lysa på cellen och se var ämnet tagit vägen. Detta visade sig inte vara en bra metod, då den fluorescenta delen var för stor och påverkade naftoxylosidens biologiska och fysikaliska egenskaper för mycket. Istället märkte vi in föreningarna med radioaktivt väte. De radioaktivt inmärkta analogerna påverkar inte de fysikaliska egenskaperna och är därför ett bättre sätt att följa ämnena i cellerna. Vi har studerat dessa molekyler i celler och våra preliminära resultat visar att friska och sjuka celler beter sig mycket olika. Bland annat går mekanismerna i de cancersjuka cellerna mycket snabbare. Med resultaten från denna studie hoppas vi kunna förstå mer om den tumörhämmande effekten hos naftoxylosider och på det sättet kunna utveckla bättre cancermediciner. Detta arbete inkluderar också ett antal undersökningar i syfte att i detalj förstå hur vissa kemiska reaktioner går till. För att göra detta har vi utvecklat dels nya metoder för att mäta mängden organisk förening och dels nya metoder för att bygga organiska molekyler. The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Organic chemistry (S/LTH) (011001240)
id
500f5811-818e-4491-8ff7-8ce9f1d32f36 (old id 1051679)
date added to LUP
2016-04-04 11:13:01
date last changed
2023-04-18 18:31:22
@phdthesis{500f5811-818e-4491-8ff7-8ce9f1d32f36,
  abstract     = {{Labeled analogs to an antiproliferative naphthoxyloside have been synthesized and evaluated. Our investigations have shown that the fluorescently labeled analogs are poor structural analogs, and the physical and biological properties are altered to a large extent. Instead, a radioactively labeled compound was synthesized, which made it possible to follow the pathway in the cell. The results showed a difference between a normal and a transformed cell line based on accumulation of the naphthoxyloside and it appears that the transformed cells process the naphthoxylosides faster than the normal cells do.<br/><br>
<br/><br>
This work also involved mechanistic studies for regioselective openings of benzylidene acetals with boranes and a new mechanism has been proposed. As it turns out, the regioselectivity can be controlled by the choice of borane, Lewis acid and solvent. When the borane is activated by a Lewis acid, the reaction rate is increased and the borane is the most electrophilic species, thus directing the regioselectivity. In contrary, when the borane is not activated, the Lewis acid is the most electrophilic species that directs the regioselectivity.}},
  author       = {{Johnsson, Richard}},
  isbn         = {{978-91-628-7473-5}},
  keywords     = {{Fluorescent xylosides; Carbohydrates; Naphthoxylosides; Cancer; Mechanistic studies; Radioactive xylosides; Acetals}},
  language     = {{eng}},
  publisher    = {{Organic Chemistry, Lund University}},
  school       = {{Lund University}},
  title        = {{Synthetic studies on naphthoxylosides - labeled compounds and mechanistic studies on acetals}},
  url          = {{https://lup.lub.lu.se/search/files/5721633/1051680.pdf}},
  year         = {{2008}},
}