A route to carbon-linked disaccharides (two monosaccharide units linked by a carbon bridge rather than a glycosidic oxygen) employing nitrile oxide/isoxazoline chemistry has been investigated. This convergent approach is based on cycloaddition of sugar-derived alkene and nitrile oxide fragments, followed by ring cleavage and functional group manipulation of the resulting 2-isoxazoline. Careful selection of the nitrile oxide and alkene fragments defines much of the stereochemistry of the products. Two ω-unsaturated hexofuranoses were chosen for study: 3-<i>O</i>-benzyl-5,6-dideoxy-1,2-<i>O</i>-isopropylidene-α-D-<i>xylo</i>-hex-5-enofuranose (<i>37</i>) derived from D-glucose and methyl 5,6-dideoxy-2,3-<i>O</i>-isopropylidene-α-D-<i>lyxo</i>-hex-5-enofuranoside (<i>137</i>), which has the opposite configuration to (<i>37</i>) at C_2, derived from D-mannose. Four nitrile oxides were employed in cycloadditions to these alkenes: ethoxycarbonylformonitrile oxide (<i>36</i>) was used as a model 1,3-dipole to probe the π-facial selectivity of cycloadditions to alkene (<i>137</i>), and three pyranose 1-nitrile oxides (<i>122</i>), (<i>146</i>) and (<i>150</i>), derived from D-xylose, D-arabinose and D-galactose respectively. Additions to alkene (<i>37</i>) proceeded with a high degree of π-facial selectivity (56-82% d.e.) in favour of the 2-isoxazoline with <i>erythro</i> configuration. Similar selectivity was noted in additions to alkene (<i>137</i>). This selectivity can be explained in terms of the 'inside alkoxy effect' proposed by Houk and modified to include the 'homoallylic effect' put forward by De Micheli. Reductive hydrolytic cleavage of the 2-isoxazolines to release the latent β-hydroxy ketone functionality was carried out by both Pd/C and Ra-Ni catalysed hydrogenolysis. In the Pd/C case significant loss of the 3-<i>O</i>-benzyl protecting group was noted, however, Ra-Ni hydrogenolysis afforded the required β-hydroxy ketones (1→6)-carbonyl-linked <i>C</i>-disaccharides) in moderate yield (43-56%) along with a minor product identified as an epimeric mixture of the corresponding γ-amino alcohols ((1→6)-aminomethylene-linked <i>C</i>-disaccharides). Finally, reduction of the β-hydroxy ketone functionality and subsequent removal of the isopropylidene protecting groups afforded the dipyranose (1→6)-hydroxymethylene-linked <i>C</i>-disaccharides.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:660517 |
| Date | January 1993 |
| Creators | Penman, Kenneth J. |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/11249 |
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