Novel methodologies for the synthesis of C-aryl glycosides and progress toward the synthesis of the C-aryl glycoside natural products galtamycinone and kidamycin

The development of methodologies for the synthesis of C-aryl glycosides has been described. Novel C-aryl glycosides were prepared by [4+2] cycloadditions between benzynes and glycosyl-substituted furans. A modification of the cycloaddition approach, wherein the two reactants were linked via a cleavable tether, allowed C-aryl glycosides to be prepared in a highly regioselective manner. An alternate method for the preparation of C-aryl glycosides via an SN2' ring opening reaction of benzyne/furan cycloadducts with sugar nucleophiles has been described. Extension of the benzyne/glycosyl-substituted furan cycloaddition methodology to natural product synthesis has been described. A formal total synthesis of the antitumor antibiotic galtamycinone has been completed. Application of the cycloaddition methodology toward the total synthesis of the bis-C-aryl glycoside antitumor antibiotic kidamycin has also been described.