PART I. A deuterium exchange analysis of 2,5-dihydroxyacetanilide (5)
in the absence and presence of DHAE II was performed to test the
nucleophilicity of the substrate in the absence and presence of catalyst. In
addition, inhibition studies using 1,4-dihydroxybenzene were performed to
determine the role that the N-acetyl side chain group plays in the formation of a stable substrate-enzyme complex. 1,4-Dihydroxybenzene was found to be a
weak inhibitor, indicating that the N-acetyl functionality may play a crucial role in forming stable enzyme-substrate interactions. The synthesis of
dihydroquinoline 7 was pursued to investigate the enzyme substrate interactions
between DHAE and a substrate where the N-acetyl side chain has been fixed to a
particular orientation. Efforts towards formation of the C6-C7 bond as a key
step in the synthesis of dihydroquinoline 7 using palladium couplings,
organocuprates, Lewis acid catalysts, and aza-Claisen reactions were pursued.
To complement the results obtained, the electron distribution in amide 21 was
calculated using Semi Empirical methods. The results revealed that the electron
density in the aromatic ring is centered around C4, suggesting that this is the
most nucleophilic carbon in the ring.
PART II. Slagenins A (1), B (2), and C (3) were synthesized by β-functionalization
of olefin 14. The desired tetrahydrofuroimidazolidin-2-one system was achieved by intramolecular oxidative addition of alcohol 4 to the
imidazolone ring. When this reaction was carried out in the presence of
methanol slagenins B (2) and C (3) were obtained in good yield. Heating 2 and
3 in aqueous acid gave slagenin A (1) as the sole product. (Z)-debromoaxinohydantoin (17) was synthesized by intramolecular cyclization of
α-methoxy imidazolone 11b under acidic conditions followed by a double
oxidation reaction to furnish the hydantoin-lactam functionality. These
conditions were originally developed for a practical synthesis of the related
alkaloid (Z)-debromohymenialdisine (20). A series of acid and base catalyzed
reactions of imidazoles bearing an α-β unsaturated system or a β-halogen
functionality showed that cyclizations via an S[subscript N]2 path favor formation of an
oxazoline ring system. Preliminary studies using pyrrolocarboxamideacetals
suggest that β-ketone 73 would be an appropriate substrate for the formation of
the pyrrolopyrazine system in the agelastatins. / Graduation date: 2002
| Identifer | oai:union.ndltd.org:ORGSU/oai:ir.library.oregonstate.edu:1957/29980 |
| Date | 21 August 2001 |
| Creators | Barrios Sosa, Ana Carolina |
| Contributors | Horne, David A., Gable, Kevin P. |
| Source Sets | Oregon State University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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