General approach to the synthesis of persubstituted hydrophilic and amphiphilic beta-cyclodextrin derivatives

Heptakis(2,3,6-tri-O-allyl)-beta-cyclodextrin 2 was converted to heptakis[2,3,6-tri-O-(2,3-dihydroxypropyl)]-beta-cyclodextrin 3 by osmium tetroxide-catalyzed dihydroxylation. A diastereomeric mixture of 3 was treated with sodium periodate followed by sodium borohydride to give heptakis[2,3,6-tri-O-(2-hydroxyethyl)]-beta-cyclodextrin 5 in 86% yield. Compound 5 could be quantitatively transformed into heptakis(2,3,6-tri-O-carboxymethyl)-beta-cyclodextrin 6 by TEMPO-mediated oxidation. The same reaction sequence was also applied to heptakis(2,6-di-O-allyl-3-O-methyl)-beta-cyclodextrin 8, heptakis(2,3-di-O-allyl-6-O-methyl)-beta-cyclodextrin 12, and heptakis(2,3-di-O-allyl-6-O-butyl)-beta-cyclodextrin 16; the analogous corresponding hydroxyethyl and carboxymethyl derivatives were isolated in high yields. All products were proved to be chemically uniform.