A novel concise total synthesis of (+)-lentiginosine

Total synthesis of (+)-lentiginosine via a key Au catalysis

“…It belongs to a class of bicyclic azasugars, including swainsonine (2) and castanospermine (3), that possess significant medical potential and have attracted intense synthetic efforts. Various total syntheses of (+)-lentiginosine has been achieved over the years using creative strategies [2][3][4][5][6][7][8][9][10][11].…”

Synthesis of 1,2-Dihydroxyindolizidines from 1-(2-Pyridyl)-2-propen-1-ol

“…6 On this ground, many syntheses of lentiginosine have been described, and apart from a few enantioselective procedures, most of them are based on chiral pool starting materials. 3,5b Nevertheless, after the first approach of Shibasaki and co-workers 7 starting from a dihydropyridone derivative, some processes exploiting suitably functionalized nonchiral pyridines as precursors have been reported for the synthesis of natural (+)-lentiginosine, 8 swainsonines, 9 benzo-fused hydroxyindolizidines, 10 and more recently (−)-lentiginosine and its epimers. 11 On the whole, the synthesis of indolizidine derivatives from pyridines is quite sparse, and only a few examples have been reported.…”

“…In this context, natural (+)-lentiginosine, isolated in 1990 from the leaves of Astragalus lentiginosus , was found to be a potent and selective inhibitor of the fungal α-glucosidase, amyloglucosidase, while recent results showed that the nonnatural enantiomer (−)-lentiginosine acts as an apoptosis inducer on tumor cells of a different origin . On this ground, many syntheses of lentiginosine have been described, and apart from a few enantioselective procedures, most of them are based on chiral pool starting materials. ,5b Nevertheless, after the first approach of Shibasaki and co-workers starting from a dihydropyridone derivative, some processes exploiting suitably functionalized nonchiral pyridines as precursors have been reported for the synthesis of natural (+)-lentiginosine, swainsonines, benzo-fused hydroxyindolizidines, and more recently (−)-lentiginosine and its epimers . On the whole, the synthesis of indolizidine derivatives from pyridines is quite sparse, and only a few examples have been reported …”

(+)‐Lentiginosine, a Potent and Selective Inhibitor of Amyloglucosidase: Synthetic Efforts and Disputes on Its Absolute Configuration

“…A very concise enantioselective total synthesis of (+)‐lentiginosine was achieved by Zhou and coworkers72 and based on ethyl 3‐(pyridine‐2‐yl)acrylate N ‐oxide ( 138 ), derived from picolinaldehyde ( 137 ), as the starting material, and on an improved Sharpless asymmetric dihydroxylation as the key step (Scheme ). Asymmetric dihydroxylation, performed with a higher excess of (DHQ) 2 PHAL and K 2 CO 3 compared to the usual AD system, gave diol 139 with >99.9 % ee .…”