- Improved Synthesis of C2 and C6 Monoderivatives of α- And β-Cyclodextrin via the Click Chemistry Approach
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An efficient multigram-scale azide-alkyne coupling of cyclodextrin derivatives mono-6-azido-6-deoxy-β-cyclodextrin, mono-2-O-propargyl-β-cyclodextrin, and mono-2-O-propargyl-α-cyclodextrin with terminal alkynyl aryl ethers or azides, mediated by copper(I) is reported. This process uses a stoichiometric ratio of substrates and 5 mol% of the copper catalyst to give the products with full conversion; thus, no chromatographic purification is necessary. The yields of both α- and β-cyclodextrin derivatives are in the range of 80 to 99%.
- Chmurski, Kazimierz,Stepniak, Pawel,Jurczak, Janusz
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p. 1838 - 1843
(2015/06/30)
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- Intermolecular interactions between doxorubicin and β-cyclodextrin 4-methoxyphenol conjugates
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Newly synthesized derivatives of β-cyclodextrin, mono(6-deoxy-6-(1-1, 2,3-triazo-4-yl)-1-propane-3-O-(4-methoxyphenyl))β-cyclodextrin (1) and mono(6-deoxy-6thio(1-propane-3-O-(4-methoxyphenyl))) β-cyclodextrin (2) were designed to be receptors of the anticancer drug doxorubicin, which could potentially decrease the adverse effects of the drug during treatment. In both aqueous and aqueous dimethyl sulfoxide (DMSO) solutions, doxorubicin forms an inclusion complex with the new cyclodextrin derivatives with formation constants of Ks = 2.3 × 104 and Ks = 3.2 × 105 M-1 for cyclodextrins 1 and 2, respectively. The stabilities of the complexes are 2-3 orders of magnitude greater than those with native β-cyclodextrin, and the flexibility of the linker of the side group of the cyclodextrins contributes to this stability. In a hydrogen-bond- accepting solvent, such as pure DMSO, an association that includes hydrogen bonding and chloride ions is favored over the binding of doxorubicin in the cavity of the cyclodextrin derivative. This contrasts with an aqueous medium in which a strong inclusion complex is formed. Cyclic voltammetry, UV-vis, 1H NMR, and molecular modeling studies of solutions in DMSO and of solutions in water/DMSO demonstrated that the two different modes of intermolecular interaction between doxorubicin and the cyclodextrin derivative depended on the solvent system being utilized.
- Swiech, Olga,Mieczkowska, Anna,Chmurski, Kazimierz,Bilewicz, Renata
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experimental part
p. 1765 - 1771
(2012/05/20)
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