Comprehensive Summary 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...Comprehensive Summary 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 3β,6β-dihydroxy-Δ7-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.展开更多
Comprehensive Summary 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 l...Comprehensive Summary 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 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 CO_(2)-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 theβ-selective installation of the(1→2)-linked disaccharide onto the steroidal C3β-OH with the corresponding disaccharideα-imidates were also examined,however,formation of theα-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.展开更多
基金the financial support from the National Natural Science Foundation of China(21901251)Shanghai Sailing Program(19YF1458400)Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science andTechnology(LMDBKF201803).
文摘Comprehensive Summary 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 3β,6β-dihydroxy-Δ7-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.
基金the financial support from the National Natural Science Foundation of China(21901251)Shanghai Sailing Program(19YF1458400)Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology(LMDBKF201803).
文摘Comprehensive Summary 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 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 CO_(2)-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 theβ-selective installation of the(1→2)-linked disaccharide onto the steroidal C3β-OH with the corresponding disaccharideα-imidates were also examined,however,formation of theα-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.