Selective Functionalization and Flexible Coupling of Cyclodextrins at the Secondary Hydroxyl Face

• Published in: Journal of organic chemistry Vol. 60; no. 20; pp. 6537 - 6545
• Main Authors: van Dienst, Erik van, Snellink, Bianca H. M, von Piekartz, Irma, Gansey, Marcel H. B. Grote, Venema, Fokke, Feiters, Martinus C, Nolte, Roeland J. M, Engbersen, Johan F. J, Reinhoudt, David N
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.10.1995; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; ALPHA-CYCLODEXTRIN; SIDE; COMPLEX; ACID DISSOCIATION; STRONG BINDING; ENANTIOMERS; DIMETHYL-BETA-CYCLODEXTRIN; BEARING; DIMERS; DERIVATIVES
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo00125a045

Methods are described for the chemo- and regioselective monofunctionalization of the secondary hydroxyl face of cyclodextrins. Monofunctionalization takes place either by nucleophilic epoxide opening of mono(2(A),3(A)-anhydro)heptakis(6-O-tert-butyldimethylsilyl)-(2(A)S)-beta-cylodextrin by ethylenediamine, lithium azide, or ammonia or by direct monoalkylation of one of the C(2)-hydroxyl groups of heptakis(6-O-tert-butyldimethylsilyl)cyclodextrins with primary alkyl bromides, with cyano-, ethynyl-, or ester-containing functional groups. The latter route enables the synthesis of mono(2(A)-O-(alpha-(4-(aminomethyl)tolyl))hexakis(2(B),2(C),2(D),2(E),2(F),2(G),-O-methyl)heptakis(6-O-tert-butyldimethylsilyl)-beta-cyclodextrin and its 2-aminomethyl isomer. These are lipophilic precursors for cyclodextrin derivatives having one reactive functional group and an enlarged molecular cavity formed by partial methylation of the secondary hydroxyl face. The direct monoalkylation route of the secondary face leaves the structure of the cavity intact, while this is distorted in the route using nucleophilic epoxide opening. Two amino-functionalized cyclodextrins were used for coupling reactions with a monofunctionalized calix[4]arene. In this way water-soluble cyclodextrin derivatives could be obtained of which the secondary faces were flexibly capped with a calix[4]arene moiety.