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Dissertation
Studies directed towards the synthesis of polyhydroxylated indolizidines (Pt.1) ; tandem nitroaldol/Diels-Alder reactions of nitroethylene derivatives (Pt.2)
Doctor of Philosophy (Ph.D.), Drexel University
Jun 1998
DOI:
https://doi.org/10.17918/00009252
Abstract
Part I. The synthesis of polyhydroxylated indolizidines using 4-oxygenated 4,5-dihydroisoxazole (DHI) intermediates derived from carbohydrate precursors was investigated. To begin a bicyclic DHI ring was constructed by nitrosative cyclization of a ribofuranoside which contained an iodo group located [gamma] to a tosyl group. Reaction of the ribofuranoside with a mixture of excess sodium nitrite and n-propyl nitrite in DMSO afforded displacement of iodine by nitrite, nitrosation, and cyclization of oxime anion with displacement of the tosyl group. The optically active bicyclic DHI was obtained in 43% yield. In order to furnish the additional three carbons needed for the targeted indolizidines, the nitro group of the bicyclic DHI was displaced by an acetylide derived from an O-protected propargyl alcohol derivative. Catalytic hydrogenation of the alkyne group followed by hydride reduction of the DHI ring afforded exclusively one isomer of the [gamma]-amino alcohol, the precursor to 1-deoxy-8a-epicastanospermine. Removal of the acetal moiety of the [gamma]-amino alcohol with trifluoroacetic acid was possible. The resulting triol was acetylated furnishing the triacetate in 35% yield for which the structure could be readily established. Part II. A general one-pot procedure for the in-situ generation of nitroethylene derivatives and their use as dienophiles in the Diels-Alder reaction was developed. The nitroethylene derivatives which were generated include (1-nitroethenyl)sulfonyl benzene, ethyl 2-nitropropenoate, and (1-nitroethenyl)phenyl methanone. Generation involved condensation of formalin with the appropriate nitromethane derivative. When generation was conducted in the presence of diene and acetic acid, cycloadducts substituted with sulfone, ester, and ketone groups were obtained. Dienes used included cyclopentadiene, 2,3-dimethyl-1,3-butadiene, isoprene, and 1,3-cyclohexadiene. Synthetic transformations of [alpha]-nitrosulfone cycloadducts involving sulfone group replacement by carbon nucleophiles were also carried out. Several [beta],[gamma]-unsaturated [alpha]-nitrosulfones were prepared. The dianion of phenylsulfonylnitromethane, generated using excess LDA, afforded the non-conjugated [beta],[gamma]-unsaturated [alpha]-nitrosulfones, upon treatment with aldehydes followed by acetic acid. Bis (nitrosulfone) byproducts were also detected in these reactions, apparently arising from Michael condensation of phenylsulfonylnitromethane with [alpha],[beta]-unsaturated [alpha]-nitrosulfone intermediates.
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Details
- Title
- Studies directed towards the synthesis of polyhydroxylated indolizidines (Pt.1) ; tandem nitroaldol/Diels-Alder reactions of nitroethylene derivatives (Pt.2)
- Creators
- Sharmila Shah-Patel
- Contributors
- Peter A. Wade (Advisor) - Drexel University, Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xvi, 231 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- College of Arts and Sciences; Drexel University
- Other Identifier
- 991021889069404721