Total Synthesis of Starfish Cyclic Steroid Glycosides. Part 3, Formal Total Synthesis of Luzonicosides A and D

Luzonicosides A (1) and D (2) are the major saponins isolated from pacific starfish Echinaster Luzonicus, featuring a sterically congested 16-membered ring which is formed by bridging the C3 and C6 of a 3 beta,6 beta-dihydroxy-delta(7)-ene steroid with a 1,2-trans-linked linear trisaccharide via glycosidic and ether bonds, respectively. Here, we describe a formal total synthesis of starfish cyclic steroid glycosides 1 and 2. The synthetic route is highly modular and versatile, involving construction of the 16-membered macrocycles via Au(I)-catalyzed intramolecular glycosylation, highly efficient installation of unsaturated sugar moieties with ortho-hexynylbenzoates, elaboration of glucuronic acid unit via post-oxidation, and a de novo synthesis of the ether-linked pyranose unit.