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Cyclodextrin‐based carbohydrate clusters by amide bond formation
Author(s) -
Fulton David A.,
Pease Anthony R.,
Stoddart J. Fraser
Publication year - 2001
Publication title -
israel journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.908
H-Index - 54
eISSN - 1869-5868
pISSN - 0021-2148
DOI - 10.1560/26tf-06hg-eqjj-w85j
Subject(s) - chemistry , cyclodextrin , amide , lactose , medicinal chemistry , stereochemistry , organic chemistry
Per‐6‐amino‐2,3‐dimethyl‐ß‐cyclodextrin was prepared very efficiently as its hydrochloride salt from native ß‐cyclodextrin in four steps and 89% overall yield. O ‐Acetyl‐protected ß‐D‐thioglucose and ß‐D‐thiolactose derivatives, containing short spacer arms terminated with carboxylic acid functions, were prepared by the BF 3 ·OEt 2 ‐catalyzed thioglycosylation of ß‐D‐glucose pentaacetate and ß‐lactose octaacetate with 3‐mercaptopropionic acid, respectively. Utilizing amide bond formation as the key step, these thio‐ß‐D‐glucosyl and lactosyl derivatives were coupled to per‐6‐amino‐2,3‐dimethyl‐ß‐cyclodextrin to afford, after deprotection, perfunctionalized ß‐cyclodextrin‐based clusters containing seven thio‐ß‐D‐glucosyl and seven ß‐lactosyl appendages, respectively. Molecular modeling of both these ß‐cyclodextrin‐based clusters revealed the glucose and lactose clusters to be approximately 23 Å and 27 Å in diameter, respectively, and approximately 19 Å in height in both cases. The association constants for the complexation of the anti‐inflammatory drug naproxen by ß‐cyclodextrin, per‐2,3‐dimethyl‐ß‐cyclodextrin, and the lactose cluster of ß‐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.