%0 Journal Article
%A Denmark, Scott E.
%A Martinborough, Esther A.
%D 1999
%T Enantioselective Total Syntheses of (+)-Castanospermine,
(+)-6-Epicastanospermine, (+)-Australine, and (+)-3-Epiaustraline
%U https://acs.figshare.com/articles/journal_contribution/Enantioselective_Total_Syntheses_of_-Castanospermine_-6-Epicastanospermine_-Australine_and_-3-Epiaustraline/3672534
%R 10.1021/ja9829970.s002
%2 https://ndownloader.figshare.com/files/5762295
%K alkaloids
%K functionalized nitroso acetals
%K Synthese
%K combination
%K material
%K Castanospermine
%K australine
%K tandem nitroalkene cycloaddition process
%K yield
%K Australine
%K sequence
%K indolizidine
%K access
%K ability
%K hydrogenolysi
%K protection
%K chiral
%K novel silaketal tether
%K Epiaustraline
%K glycosidase
%K bicyclic systems
%K diastereocontrol
%K epiaustraline
%K strategy
%K epicastanospermine
%K dihydrofuran
%K inhibitor
%K Enantioselective
%K castanospermine
%K silaketal nitro olefin 18
%K Epicastanospermine
%K pyrrolizidine
%K synthese
%K placement
%X 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.
%I ACS Publications