A convergent route, based on nitrile oxide/isoxazoline chemistry to carbon-linked disaccharides (<I>C</I>-disaccharides) and <I>C</I>-glycosides with functionalised linkages has been investigated. The sequence involves three steps. Firstly, the cycloaddition of a sugar-derived nitrile oxide to a terminal alkene provides a 3,5-disubstituted 2-isoxazoline. Next, the substituents attached to the isoxazoline may be modified, and finally the heterocycle subjected to either hydrogenolysis or reductive cleavage to afford a <I>C</I>-glycoside with a carbonyl or an amino functionalised linkage. Four terminal alkenes were selected; two ω-unsaturated monosaccharide derivatives, methyl 5, 6-dideoxy-2,3-<I>0</I>-isopropylidene-α-D-<I>lyxo</I>-hex-5-enofuranoside (93) and 3-<I>O</I>-benzyl-5, 6-dideoxy-2, 3-<I>O</I>-isopropylidene-α-D-<I>xylo</I>-hex-5-enofuranose (84), and two non-carbohydrate model alkenes, methylenecyclohexane and styrene. The <I>in situ</I> Mukaiyama dehydration of the peracetylated 2,6-anhydro-1-deoxy-1-nitroalditol derivatives from nitromethane and D-xylose, D-galactose and D-mannose provided the source of nitrile oxides (79), (89) and (90) respectively. Cycloadditions of the xylopyranosyl and galactopyranosyl nitrile oxides (79) and (89) to alkenes (93) and (84) proceeded regiospecifically and with a high degree of π-facial selectivity (40-64% d.e.). In each case the major adduct was found to possess <I>R</I>-configuration at the newly formed chiral centre C-5, corresponding to an <I>erythro </I>relationship between it and the adjacent C-4 position of the attached furanose unit. The structure of the isoxazoline formed from xylopyranosyl nitrile oxide (79) and D-mannose derived alkene (93) was established by X-ray crystallography. The observed selectivies may be rationalised in terms of the "inside alkoxy effect" proposed by Houk and the "homoallylic" modification of De Micheli <I>et al.</I>
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:650850 |
| Date | January 1996 |
| Creators | Ferguson, William James |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/13815 |
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