Synthesis of water soluble O-glycosides of N-(hydroxyalkyl)aminomethylferrocenes

Abstract

A series of water soluble ferrocenylamine–glucose conjugates, [N-2-(β-D-glucopyranosyloxy)ethyl-, [N-3-(β-D-glucopyranosyloxy)propyl-, [N-5-(β-D-glucopyranosyloxy)pentyl-N-methylaminomethyl]ferrocene, has been synthesized from the methiodide salt of N,N-dimethylaminomethylferrocene and N-(3,4,6-tri-O-benzyl-β-D-glucopyranosyloxy-ethyl, -propyl and -pentyl)amine respectively. N-Methylation of the products from the latter reaction was achieved by formylation followed by reduction with lithium aluminium hydride. Catalytic hydrogenolysis over palladium removed the benzyl protecting groups from the carbohydrate moiety to give the target conjugates. An alternative synthesis of [N-2-(β-D-glucopyranosyloxyethyl)aminomethyl]ferrocene using boron trifluoride–diethyl ether promoted glycosylation of penta-O-acetyl-D-glucopyranose and [N-(2-hydroxyethyl)-N-methylaminomethyl]ferrocene followed by deacetylation of the carbohydrate protecting group using basic ion exchange resin was also developed. The pK_a values of the water soluble conjugates were determined.