%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