Insight into the\nCourse of the Ferrier Rearrangement\nUsed to Obtain Untypical Diosgenyl Saponins

The Ferrier rearrangement was utilized to obtain 2,3-unsaturated\ndiosgenyl glycosides. This reaction proceeded with high stereoselectivity,\nyielding mostly saponins with an α configuration (hexoses) or\npredominantly with a β configuration (pentoses). The diversity\nof the glycals used and the glycosides obtained enabled a deep discussion\nof the Ferrier rearrangement mechanism. The mechanism was supported\nby DFT calculations concerning the intermediate ions. It was concluded\nthat the vinylogous anomeric effect may influence the reactivity of\nthe glycals. Two possible Ferrier rearrangement intermediates, dioxolenium\nand allyloxycarbenium ions, were hypothesized to exist in thermodynamic\nequilibrium that shifted toward the former. The allyloxycarbenium\nion participates in the final rearrangement step and determines the\nreaction regioselectivity. Furthermore, the conformational stability\nof the 2,3-unsaturated pyranose ring determines the stereoselectivity\nof the reaction. Factors influencing this stability, as well as the\nNMR data enabling recognition of the <sup>0</sup>H<sub>5</sub> and <sup>5</sup>H<sub>0</sub> conformations, were identified. Chemoselective\nhydrogenation of 2,3-unsaturated diosgenyl glycosides provided a series\nof 2,3-dideoxy analogues. The anticancer, hemolytic, and antibacterial\nactivities of the synthesized saponins are presented alongside a discussion\nof the structure–activity relationships.