Studies towards the total synthesis of Elsamicin A, B and Chartreusin

Abstract

Chartreusin, elsamicin A and elsamicin B are prominent examples of glycosidic polyketide antibiotics. They share a common aglycone connected as O-fucoside at the C11-hydroxyl group. Their antiproliferative activities against various tumor cell lines makes them interesting targets for natural product synthesis. This master thesis describes studies towards the synthesis of the carbohydrate units and formation of the gylcosidic bond between the sugar moieties and the polyketide aglycone. The synthesis of 4 of 5 building blocks proceeds through a common intermediate enone, which was prepared in 6 linear steps from commercially avaiblable fucose. The glycosyl acceptor and the trichloroacetimidate furnished one disaccharide under standard Schmidt gylcosylation conditions. Treatment of azido fucoside and diol under optimized Koenigs-Knorr conditions furnished another disaccharide. Starting from D-fucose, the synthesis of all protected saccharide units was accomplished in a highly convergent manner.