Total Synthesis of Starfish Cyclic Steroid Glycosides. Part 1, Synthesis of the Aglycone and Attempts at Installation of the Sugar Units

Sepositoside A (1) is the major and first cyclic steroid glycoside isolated from starfishes, which features a strained 16-membered ring formed by tethering C3 and C6 of the steroid aglycone with a linear trisaccharide. We conceived a convergent synthetic plan in which sepositoside A was disconnected into a disaccharide and a steroid-glucose hybrid ether. The desired 3 beta,6 beta-dihydroxy-delta(7,8)-23- one aglcyone was readily prepared from dehydroepiandrosterone in 12 steps. The etherification of the 6 beta-hydroxy-delta(7,8)-steroid with a variety of hexopyranoside-C6-electrophiles and CO2-extrusion of a steroid-pyranose hybrid carbonate were extensively studied; however, formation of the desired steroid-pyranose etherate linkage has not been successful. Model studies on the beta-selective installation of the (1 -> 2)-linked disaccharide onto the steroidal C3 beta-OH with the corresponding disaccharide alpha-imidates were also examined, however, formation of the alpha-glycosides prevailed. The present results force us to explore alternative approaches to construct the steroid-pyranose etherate linkage and stepwise assembly of the glycans en route to the starfish cyclic steroid glycosides, which will be presented in two articles that follow. (GRAPHICS)