Use this URL to cite or link to this record in EThOS:
Title: The nitrile oxide/isoxazoline route to carbon-linked disaccharides
Author: Penman, Kenneth J.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1993
Availability of Full Text:
Access from EThOS:
Full text unavailable from EThOS. Please try the link below.
Access from Institution:
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-O-benzyl-5,6-dideoxy-1,2-O-isopropylidene-α-D-xylo-hex-5-enofuranose (37) derived from D-glucose and methyl 5,6-dideoxy-2,3-O-isopropylidene-α-D-lyxo-hex-5-enofuranoside (137), which has the opposite configuration to (37) at C_2, derived from D-mannose. Four nitrile oxides were employed in cycloadditions to these alkenes: ethoxycarbonylformonitrile oxide (36) was used as a model 1,3-dipole to probe the π-facial selectivity of cycloadditions to alkene (137), and three pyranose 1-nitrile oxides (122), (146) and (150), derived from D-xylose, D-arabinose and D-galactose respectively. Additions to alkene (37) proceeded with a high degree of π-facial selectivity (56-82% d.e.) in favour of the 2-isoxazoline with erythro configuration. Similar selectivity was noted in additions to alkene (137). 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-O-benzyl protecting group was noted, however, Ra-Ni hydrogenolysis afforded the required β-hydroxy ketones (1→6)-carbonyl-linked C-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 C-disaccharides). Finally, reduction of the β-hydroxy ketone functionality and subsequent removal of the isopropylidene protecting groups afforded the dipyranose (1→6)-hydroxymethylene-linked C-disaccharides.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available