Oligosaccharide analogues of polysaccharides .14. Carbocyclic cyclodextrin analogues. Synthesis of all trimeric and tetrameric isomers by homo- and heterocoupling of 1,4-cis-diethynylated 1,5-anhydroglucitols

Hetero-or homocoupling of protected 1,4-cis-diethynylated 1,5-anhydroglucitols leads to two isomeric cyclotrimers and to four isomeric cyclotetramers. The C-3-symmetric cyclotrimer 31, the C-4-symmetric cyclotetramer 35, and the D-2-symmetric cyclotetramer 6 have been prepared before. We have now synthesized the C-1-symmetric cyclotrimer 13, and the C-1- and the C-2-symmetric cyclotetramers 22 and 27, respectively. The cyclotrimer 13 was prepared by intramolecular, oxidative homocoupling and, alternatively, by a one-pot trimerization/cyclization of the monomer 36 (Schemes 1 and 5, resp.). Oxidative homocoupling was used for the cyclization of the tetramers 19 and 25, leading to 22 and 27. The tetramer 19 was made by sequential Cadiot-Chodkiewicz coupling (Scheme 2) and the tetramer 25 by a combination of a Cadiot-Chodkiewicz reaction and an intermolecular, oxidative homocoupling (Scheme 3). The acetates 34 and 38, corresponding to 35 and 27, respectively, were also made by a one-per dimerization/cyclization of the dimer 37 (Scheme 5). Intramolecular oxidative heterocoupling is also feasible and results in an alternative, more convenient synthesis of the acetylated cyclotrimer 30 and the acetylated cyclotetramer 34 (corresponding to 31 and 35, resp.; Scheme 4). The solid-state conformation of the C-4-symmetric cyclotetramer 34 corresponds well to the one predicted by force-field calculations. We compared the water-solubilities of the cyclotrimers 13 and 31 and the tetramers 6, 22, 27, and 35, their calculated conformations (MM3(*)) and the D-adenosine binding properties of the cyclotetramers 6, 27, and 35.