Novel Amphiphilic Cyclodextrins: Graft‐Synthesis of Heptakis(6‐alkylthio‐6‐deoxy)‐β‐cyclodextrin 2‐Oligo(ethylene glycol) Conjugates and Their ω‐Halo Derivatives

Novel amphiphilic cyclodextrins were synthesised by grafting oligo(ethylene glycol) units onto the secondary side of heptakis(6-alkylthio-6-deoxy)-β-cyclodextrins (alkyl = ethyl, hexyl, dodecyl and hexadecyl). The oligo(ethylene glycol) substituents were introduced by reaction of heptakis(6-alkylthio-6-deoxy)-β-cyclodextrins with ethylene carbonate in the presence of potassium carbonate at elevated temperatures. The resulting oligo(ethylene glycol)-cyclodextrin conjugates were characterised by 1H NMR and 13C NMR, COSY and HSQC spectroscopy, and mass spectrometry. Addition of ethylene carbonate occurs exclusively at OH2 and results in a degree of substitution of 8−22 ethylene glycol units per cyclodextrin. Also, the ω-bromo and ω-iodo derivatives of heptakis[6-deoxy-6-hexylthio-2-oligo(ethylene glycol)]-β-cyclodextrin were prepared as strategic synthetic intermediates. The observation that seven halogen atoms are introduced per cyclodextrin provides strong evidence for the grafting of oligo(ethylene glycol) to each of the seven glucose units in the cyclodextrin ring.

[1]  Bruno Perly,et al.  Cholesteryl-cyclodextrins: synthesis and insertion into phospholipid membranes , 1999 .

[2]  C. Créminon,et al.  New amphiphilic derivatives of cyclodextrins for the purpose of insertion in biological membranes: the “Cup and Ball” molecules , 1998 .

[3]  R. Darcy,et al.  Cyclodextrin Bilayer Vesicles. , 2000, Angewandte Chemie.

[4]  H. Schneider,et al.  NMR Studies of Cyclodextrins and Cyclodextrin Complexes. , 1998, Chemical reviews.

[5]  J. Lehn,et al.  An approach to channel-type molecular structures. Part 3. Incorporation studies of the bouquet-shaped BM and BCD in phosphatidylcholine vesicles , 1993 .

[6]  M. Petty,et al.  Monolayer and multilayer films of cyclodextrins substituted with two and three alkyl chains , 1995 .

[7]  R. Auzély-Velty,et al.  Micellization of Hydrophobically Modified Cyclodextrins. 1. Micellar Structure , 2000 .

[8]  R. Darcy,et al.  Amphiphilic 6-S-alkyl-6-thiocyclodextrins: unimolecular micellar and reverse micellar behaviour , 1998 .

[9]  V. T. D'Souza,et al.  A convenient method for functionalization of the 2-position of cyclodextrins , 1990 .

[10]  J. Defaye,et al.  Selective Halogenation at Primary Positions of Cyclomaltooligosaccharides and a Synthesis of Per‐3,6‐anhydro Cyclomaltooligosaccharides , 1991 .

[11]  C. Müller-Goymann,et al.  Properties and Structure of Aqueous Solutions of Hydroxypropyl-beta-Cyclodextrin , 1993 .

[12]  D. Lasič.  Sterically Stabilized Vesicles , 1994 .

[13]  R. Darcy,et al.  Cyclodextrin liquid crystals: synthesis and self-organisation of amphiphilic thio-β-cyclodextrins , 1993 .

[14]  K. Fukuda,et al.  Formation and Deposition of Monolayers of Amphiphilic β-Cyclodextrin Derivatives , 1986 .

[15]  A. Hedges.  Industrial Applications of Cyclodextrins. , 1998, Chemical reviews.

[16]  J. Valleton,et al.  Scanning force microscopy investigation of amphiphilic cyclodextrin Langmuir-Blodgett films , 1996 .

[17]  Dominique Duchêne,et al.  Development of a new colloidal drug carrier from chemically-modified cyclodextrins: Nanospheres and influence of physicochemical and technological factors on particle size , 1996 .

[18]  Ronald Breslow,et al.  Selective sulfonation of a secondary hydroxyl group of β-cyclodextrin , 1982 .

[19]  A. Coleman,et al.  Mixed Monolayers of Amphiphilic Cyclodextrins and Phospholipids: II. Surface Potential–Area Behavior of Per-(6-amino-2,3-di-O-hexyl) β-CD Hydrochloride Salt and 1,2 Dipalmitoyl, 3-sn-Phosphatidic Acid Mixed Monolayers , 1996 .

[20]  M. Skiba,et al.  Structural Properties of Several Amphiphile Cyclodextrins and Some Related Nanospheres. An X-ray Scattering and Freeze-Fracture Electron Microscopy Study , 1998 .

[21]  A. Coleman,et al.  Mixed monolayers of amphiphilic cyclodextrins and phospholipids. I: Miscibility under dynamic conditions of compression , 1996 .

[22]  K. Stine,et al.  Comparison of host-guest Langmuir-Blodgett multilayer formation by two different amphiphilic cyclodextrins , 1996 .

[23]  R. Friedman.  A Chemically Modified Cyclodextrin , 1988 .

[24]  A. Coleman,et al.  Self-assembling systems of the amphiphilic cationic per-6-amino-.beta.-cyclodextrin 2,3-di-O-alkyl ethers , 1992 .

[25]  A. Coleman,et al.  Supramolecular assemblies based on amphiphilic cyclodextrins , 1993 .

[26]  H. Sasabe,et al.  Monomolecular layer formation of amphiphilic cyclodextrin derivatives at the air/water interface , 1999 .

[27]  Pierre Tchoreloff,et al.  Amphiphilic Monolayers of Insoluble Cyclodextrins at the Water/Air Interface. Surface Pressure and Surface Potential Studies , 1995 .