Enantioselective total synthesis of diospongins, towards the enantioselective total synthesis of solandelactones and an expedient synthesis of eantioenriched substituted (benzofuran-yl)- aryl and heteroaryl carbinols

Abstract

Thesis title: Enantioselective total synthesis of diospongins, towards the enantioselective total synthesis of solandelactones and an expedient synthesis of eantioenriched substituted (benzofuran-yl) aryl and heteroaryl carbinols. This thesis comprises three chapters and describes in sequence a) the enantioselective total synthesis of diospongin A, B and their enantiomers, b) towards the enantioselective total synthesis of solandelactones and c) an expedient synthesis of eantioenriched substituted (benzofuran-yl) ary and heteroary carbinols. Chapter I deals with the total synthesis of diospongin A, B and their enantiomers using organo catalytic / hetero-Diels-Alder reactions. Chapter II deals with the development of protocol for the preparation of key intermediates of solandelactone A, B via a catalytic asymmetric cyclopropanation and catalytic asymmetric reduction. Chapter III illustrates the synthesis of eantioenriched substituted (benzofuran-yl) aryl and heteroaryl carbinols. Chapter I: A Flexible enantioselective total synthesis of diospongins A, B and their enantiomers using catalytic Hetero-Diel-Alder / Rh-catalyzed 1,4-addition and asymmetric transfer hydrogenation reactions as key steps. C-aryl glycoside natural products diospongins A (2) and B (1) which were isolated from the rhizomes of Diocorea spongiosa through a bioassay-guided fractionation show promising antiosteoporotic activity (45Ca release at 200 and#956;M (30.5%) and 20 and#956;M (18.2%), hence, can be considered to be a lead for the discovery of potent and novel antiosteoporotic agents. Diospongins A (2) and B (1) contain a six-membered cyclic ether structural unit with 2-aryl and 6-phenacyl substitution. Despite their structural similarity, they exhibit remarkable differences in their biological profile. Diospongin B displays potent inhibitory activity on bone resorption induced by parathyroid hormone, which is comparable to that of elcitionin, a drug used clinically for osteoporosis while diospongin A did not show any activity (Figure 1)