Synthesis of 6 I-amino-6 I-deoxy-2 I–VII,3 I–VII-tetradeca- O-methyl-cyclomaltoheptaose

Abstract

The preparation of 6 I-amino-6 I-deoxy-2 I–VII,3 I–VII-tetradeca- O-methyl-cyclomaltoheptaose is reported. Two different routes (A and B), both starting from β-cyclodextrin (βCD), have been examined. Route A involved: (i) synthesis of heptakis(6- O- tert-butyldimethylsilyl)-βCD from βCD; (ii) permethylation of the secondary hydroxyl groups with methyl iodide and sodium hydride; (iii) desilylation of the primary hydroxyls with ammonium fluoride; (iv) monotosylation at O-6 position of per-(2,3- O-methyl)-βCD; (5) nucleophilic replacement of the tosyl group with azide anion; (v) reduction of the azido group by catalytic transfer hydrogenation using hydrazine hydrate in the presence of Pd/C in methanol/water. Route B started from the known 6 I-monoazido-6 I-monodeoxy-β-CD (two steps from β-CD) and entailed: (i) protection of the remaining primary hydroxyls using tert-butyldimethylsilylchloride (TBDMSCl); (ii) exhaustive methylation of the secondary hydroxyls with methyl iodide and sodium hydride; (iii) removal of the TBDMS protecting groups with ammonium fluoride; (iv) reduction of the azido group as above. Route A was found to be less convenient than Route B due to the inherent difficulty of controlling the monotosylation of per-(2,3- O-methyl)-βCD.