Regioselective self-acylating cyclodextrins in organic solvent

Abstract

Amphiphilic cyclodextrins have been synthesized with self-acylating reaction using vinyl esters in dimethylformamide. In the present study no base, catalyst, or enzyme was used, and the structural analyses using thin layer chromatography, nuclear magnetic resonance spectroscopy and mass spectrometry show that the cyclodextrin is substituted preferentially by one acyl moiety at the C2 position of the glucose unit, suggesting that cyclodextrin functions as a regioselective catalytic carbohydrate in organic solvent. In the self-acylation, the most acidic OH group at the 2-position and the inclusion complexing ability of cyclodextrin were considered to be significant. The substrate preference was also observed in favor of the long-chain acyl group, which could be attributed to the inclusion ability of cyclodextrin cavity. Furthermore, using the model amphiphilic building block, 2-O-mono-lauryl β-cyclodextrin, the self-organized supramolecular architecture with nano-vesicular morphology in water was investigated by fluorescence spectroscopy, dynamic light scattering and transmission electron microscopy. The cavity-type nano-assembled vesicle and the novel synthetic methods for the preparation of mono-acylated cyclodextrin should be of great interest with regard to drug/gene delivery systems, functional surfactants, and carbohydrate derivatization methods.

Engineered Self-Assembly of Amphiphilic Cyclodextrin Conjugates for Drug Encapsulation

“…The successful grafting of the aliphatic chains to the primary hydroxyl groups is also evident in the 13 C NMR spectra (Figure S3), as the carboxy signal appears at 172 ppm and not below 170 ppm as in the case of secondary esters . Due to the stronger nucleophilicity of the primary hydroxyl group compared to the secondary ones, esterification occurs almost selectively at the primary face.…”

“…The successful grafting of the aliphatic chains to the primary hydroxyl groups is also evident in the 13 C NMR spectra (Figure S3), as the carboxy signal appears at 172 ppm and not below 170 ppm as in the case of secondary esters. 25 Due to the stronger nucleophilicity of the primary hydroxyl group compared to the secondary ones, esterification occurs almost selectively at the primary face. Nevertheless, because of the 10fold excess of the respective chlorocarbocylic acid, a small part of the secondary hydroxyl groups also reacts as soon as the primary OH group is completely saturated.…”

Synthesis, Characterization, and Retinol Stabilization of Fatty Amide-β-cyclodextrin Conjugates

“…In particular, the stearamide modification on β-CD gives rise to a sharply declining curve and reduced cac (0.09 mM). This decline is attributed to the two hydrophobic microdomains of the β-CD cavity and the self-assembled apolar part around pyrene [12]. The cac value of O-β-CD was determined to be 0.26 mM, slightly higher than that of S-β-CD.…”

“…Based on these properties, amphiphilic CDs can be used in surface activity and solubilization, as well as in drug delivery. The amphiphilic CDs are classified as medusa-like, skirt-shaped, bouquet-shaped, ladle-type, and lollipop-style CDs according to the substitution sites and numbers [11,12]. In particular, lollipop style CDs with mono-substitution on the primary side are designed to enhance cell targeting of drug-CDs, leaving the secondary face open and accessible to guest compounds [13].…”

Access to Diosgenyl Glycoconjugates via Gold(I)-Catalyzed Etherification of Diosgen-3-yl ortho-Hexynylbenzoate

“…Amphiphilic cyclodextrins (CDs) with grafted hydrophobic moieties are a new generation of cyclodextrin derivatives compatible with biomembranes. Noteworthy, primary alcohol 2d , derived from β-cyclodextrin, a cyclic heptamer comprised of α-(1 → 4)- d -glucopyranosyl units, was treated with 1 to smoothly furnish ether 3d in 60% yield, thus opening up the prospect for modification of CDs. Galactosyl diacetonide 2e reacted with 1 to afford 3e and 3e′ in 85% and 9% yields, respectively, thus exhibiting significant improvement in yield compared to the initial synthesis .…”