Enantioselective total syntheses of (+)-castanospermine, (+)-6- epicastanospermine, (+)-australine, and (+)-3-epiaustraline

Scott E Denmark, Esther A. Martinborough

Research output: Contribution to journalArticlepeer-review

Abstract

The total syntheses of the potent glycosidase inhibitors castanospermine ((+)-1), 6-epicastanospermine ((+)-2), australine ((+)-3), and 3- epiaustraline ((+)-4) are described. The syntheses of indolizidine alkaloids (+)-1 and (+)-2 were accomplished in eight steps and in 18% and 24% overall yields from 2,5-dihydrofuran while the pyrrolizidine alkaloids (+)-3 and (+)- 4 were obtained in a nine-step sequence in 17% and 22% overall yields from the same starting material. These four natural products are derived from a single common intermediate, nitroso acetal (-)-31, which is created in the key step by the asymmetric tandem [4 + 2]/[3 + 2] cycloaddition between silaketal nitro olefin 18 and chiral vinyl ether (+)-23. The ability to access both 5,5- and 5,6-fused bicyclic systems was a result of a successful in situ N-alkylation strategy during the hydrogenolysis of four highly functionalized nitroso acetals. A novel silaketal tether provided exceptional levels of diastereocontrol and the ideal combination of protection and functional-group placement for the tandem nitroalkene cycloaddition process.

Original languageEnglish (US)
Pages (from-to)3046-3056
Number of pages11
JournalJournal of the American Chemical Society
Volume121
Issue number13
DOIs
StatePublished - Apr 7 1999

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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