Exploiting the geminal acylation reaction to produce a β-turn peptidomimetic

Elliott, Christine Elizabeth (2001) Exploiting the geminal acylation reaction to produce a β-turn peptidomimetic. Masters thesis, Memorial University of Newfoundland.

[img] [English] PDF - Accepted Version
Available under License - The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission.

Download (4MB)


The focus of this research was to develop a route to 5,6-fused 1-aza-2-oxobicycloalkane amino acids, beta-turn peptidomimetics, with carbon-based bridgehead substituents. The route that was developed proceeded as follows: Geminal acylation of the acetal derived from hex-5-en-2-one gave 2-(3-butenyl)-2-methyl-1,3-cyclopentanedione in 76% yield. Experiments with baker's yeast showed that desymmetricization of this 1,3-diketone could be carried out with very high enantioselectivity. Beckman rearrangement of (2S, 3S) 2-(3-butenyl)-3-[(tert-butyldimethylsilyl)oxy]-2-methylcyclopentanone using O-mesitylenesulfonyl hydroxylamine provided the corresponding lactam, (3S, 4S)-1-Aza-6-(3-butenyl)-5-[(tert-butyldimethylsilyl)oxy]-6-methyl-2-cyciohexanone. Cyclization of the lactam nitrogen onto the double bond was carried out with trimethylsilyl triflate and iodine in the presence of triethylamine which yielded the iodolactam (6S,5S,9S)-1-aza-5-[(tert-butyldimethylsilyl)oxy]-9-(hydroxymethyl)-6-methyl- bicyclo[4.3.0]nonan-2-one. This iodolactam was then converted into the propyl ester of (6S,5S,9S)-1-aza-5-[(tert-butyldimethylsilyl)oxy]-9-(hydroxymethyl)-6-methylbicyclo[4.3.0]nonan-2-one. The development of this route, including the elucidation of the structures of side-products, is discussed in detail.

Item Type: Thesis (Masters)
URI: http://research.library.mun.ca/id/eprint/9159
Item ID: 9159
Additional Information: Bibliography: leaves 113-117.
Department(s): Science, Faculty of > Chemistry
Date: 2001
Date Type: Submission
Library of Congress Subject Heading: Ring formation (Chemistry); Acylation

Actions (login required)

View Item View Item


Downloads per month over the past year

View more statistics