Macrocyclic derivatives with a sucrose scaffold: insertion of a long polyhydroxylated linker between the terminal 6,6′-positions

Abstract

A series of five new macrocyclic hybrids with a sucrose scaffold were prepared by the reaction of activated 1′,2,3,3′,4,4′-hexa-O-methylsucrose with diversely functionalized D-mannitols. The 21-, 25-, and 31-membered representatives containing mannitol units were prepared by a macrocyclization of 6,6′-di-O-propargylated sucrose with protected 1,6-diazido-D-mannitol or 6,6′-di-azidosucrose with propargylated D-mannitol (a “click” approach), whereas 23-membered representatives were prepared by double N-alkylation of 1′,2,3,3′,4,4′-hexa-O-methyl-6,6′-di-aminosucrose with 1,6-di-bromoacyl D-mannitol. All sucrose derivatives were tested as putative hosts for chiral recognition of α-phenylethylammonium (α-PEA) cations. In one case, in striking contrast to all sucrose-based macrocyclic hosts previously reported by us, unexpected reverse preference for the R-enantiomer was observed (K_R/K_S = 1.5).