Total Synthesis of (+)-Hyacinthacine A1 Using a Chemoselective Cross-Benzoin Reaction and a Furan Photooxygenation-Amine Cyclization Strategy

We report the shortest synthesis of glycosidase inhibitor (+)-hyacinthacine A(1) using a highly chemoselective N-heterocyclic carbene-catalyzed crossbenzoin reaction as well as a furan photooxygenation-amine cyclization strategy. This is the first such cyclization on a furylic alcohol, an unprecedented reaction due to the notorious instability of the formed intermediates. The photooxygenation strategy was eventually incorporated into a three-step one-pot process that formed the requisite pyrrolizidine framework of (+)-hyacinthacine A(1).

Automated summary

This study presents the shortest synthesis of the glycosidase inhibitor (+)-hyacinthacine A(1) using a highly chemoselective N-heterocyclic carbene-catalyzed crossbenzoin reaction and a furan photooxygenation-amine cyclization strategy. The unprecedented cyclization on a furylic alcohol due to the instability of formed intermediates was successfully achieved, eventually leading to the formation of the requisite pyrrolizidine framework through a three-step one-pot process.