The use of carbohydrates as starting materials for organic synthesis is illustrated by the synthesis of several polyhydroxylated piperidine, pyrrolidine, indolizine and pyrrolizidine alkaloids. Nucleophilic displacement by azide ion at C-2 in a D-glucose derivative, with subsequent intramolecular cyclisation through nitrogen onto the C-6 or C-5 position and functional group manipulation, led to the synthesis of: 1,5-dideoxy-1,5-imino-D-mannitol; 1,2,5-trideoxy-1,5-imino-D-arabinohexitol; 1,5-dideoxy-1,5-imino-D-glucitol; 2-Acetamido-1,5-imino-1,2,5- trideoxy-D-glucitol; 2-Acetamido-1,5-imino-1,2,5-trideoxy-D-mannitol; (2S, 3R, 4R, 5S)-3,4,5-trihydroxypipecolic acid; (2S, 3R, 4R, 5R)-3,4,5- trihydroxypipecolic acid and 2,5-dideoxy-2,5-imino-D-mannitol. Nucleophilic displacement by azide ion at C-3 in a D-glucose derivative, with subsequent intramolecular cyclisation through nitrogen onto the C-6 position, produced the tosylate salt of 3,6-dideoxy-3,6-imino-1,2-0-isopropylidene- â«-D-glucofuranose, a highly divergent intermediate, from which the pyrrolidines: 1,4-dideoxy-1,4-imino-L-gulitol, 1,4-dideoxy-1,4-imino-D-lyxitol and (2S, 3S, 4R) - 3,4-dihydroxyproline were prepared directly. Periodate cleavage of the C1-2 bond and a 2-C chain extension from C-2 with subsequent intramolecular cyclisation, produced the pyrrolizidine (IS, 2R, 8R) - 1,2-dihydroxypyrrolizidine. An intramolecular Wadsworth Emmans cyclisation between a lactol at C-1 and a phosphonate, produced by a DCC coupling of the amine with dimethoxyphosphinylacetic acid, led to the formation of the indolizine (1S, 2R, 8S, 8aR) - 1,2,8-trihydroxyoctahydroindolizine. The synthesis of 1,4-dideoxy-1,4-imino-D-lyxitol, was achieved by connection of C1 and C4 of a D-mannose derivative through nitrogen. Methyl 3,5-0-isopropylidene- â«-D-xylofuranoside was elaborated to both enantiomers of 1,4-dideoxy-1,4-imino-arabinitol. The _D-enantiomer was produced by introduction of a nitrogen between C-2 and C-5, the L- enantiomer by introduction of a nitrogen between C-1 and C-4. (2R, 3S, 4R) - 3,4-dihydroxyproline was prepared from _D-ribonolactone. The key step of the synthesis was a nucleophilic displacement by azide ion at C-2 in which the stereochemistry was unexpectedly retained.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:376945 |
| Date | January 1986 |
| Creators | Smith, Paul W. |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://ora.ox.ac.uk/objects/uuid:97dd273b-2577-4556-8889-361f801a826a |
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