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

Abstract

Comprehensive SummarySepositoside 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 3β,6β‐dihydroxy‐Δ7,8‐23‐ one aglcyone was readily prepared from dehydroepiandrosterone in 12 steps. The etherification of the 6β‐hydroxy‐Δ7,8‐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 β‐selective installation of the (1→2)‐linked disaccharide onto the steroidal C3β‐OH with the corresponding disaccharide α‐imidates were also examined, however, formation of the α‐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.