Cyclodextrin-based carbohydrate clusters by amide bond formation

Per-6-amino-2,3-dimethyl-beta -cyclodextrin was prepared very efficiently a s its hydrochloride salt from native beta -cyclodextrin in four steps and 8 9% overall yield. O-Acetyl-protected beta -D-thioglucose and beta -D-thiola ctose derivatives, containing short spacer arms terminated with carboxylic acid functions, were pre pared by the BF3.OEt2-catalyzed thioglycosylation of beta -D-glucose pentaacetate and beta -lactose octaacetate with 3-mercap topropionic acid, respectively. Utilizing amide bond formation as the key s tep, these thio-beta -D-glucosyl and lactosyl derivatives were coupled to p er-6-amino-2,3-dimethyl-beta -cyclodextrin to afford, after deprotection, p erfunctionalized beta -cyclodextrin-based clusters containing seven thio-be ta -D-glucosyl and seven beta -lactosyl appendages, respectively. Molecular modeling of both these beta -cyclodextrin-based clusters revealed the gluc ose and lactose clusters to be approximately 23 Angstrom and 27 Angstrom in diameter, respectively, and approximately 19 Angstrom in height in both ca ses. The association constants for the complexation of the antiinflammatory drug naproxen by beta -cyclodextrin, per-2,3-dimethyl-beta -cyclodextrin, and the lactose cluster of beta -cyclodextrin in 0.01 M phosphate buffered saline solution (pH 7.4) were found by UV-vis spectrophotometric titration to be 374 +/- 75 M-1,351 +/- 70 M-1, and 165 +/- 33 M-1, respectively.