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Issue 21, 2009
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Application of the Ugi four-component reaction to the synthesis of ditopic bifunctional chelating agents

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Abstract

The Ugi four-component reaction (Ugi 4CR) was exploited for the first time to obtain in a single synthetic step bifunctional ditopic chelators by using DOTA monoamide (DOTAMA) derivatives as amino and acid components. A number of ditopic systems in which the two DOTAMA units are connected by a central α-acylaminoamide group were synthesized by reacting different aldehydes, isocyanides and two DOTAMA chelates containing amino and acid functionalities. Variation of the components allows the insertion of another functional group into the α-acylaminoamide skeleton for further conjugation to biomolecules. The optimal reaction conditions were found by using methanol as solvent and ultrasound irradiation at a power of 60 W (20 kHz) for 3 h. The Gd(III) complexes of the dimeric ligands L1 and L2 (bearing a cyclohexyl ring and an octadecyl chain on the central α-acylaminoamide moiety, respectively) were fully characterized in aqueous media by relaxometric techniques with varying temperature and magnetic field strength. The relaxivity of Gd2L1 and Gd2L2 (in the aggregated form), at 20 MHz and 310 K, are 5.6 and 20.0 mM−1 s−1, respectively. The enhanced value found for Gd2L2 indicates that this lipophilic complex forms micelles at concentrations <0.1 mM. Finally, the binding of Gd2L2 to human serum albumin (HSA) was investigated by proton relaxometry, and the affinity constant of the complex and the relaxivity of the macromolecular adduct (rb1p = 38.1 mM−1 s−1; 20 MHz and 310 K) derived.

Graphical abstract: Application of the Ugi four-component reaction to the synthesis of ditopic bifunctional chelating agents

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Publication details

The article was received on 21 Apr 2009, accepted on 24 Jul 2009 and first published on 19 Aug 2009


Article type: Paper
DOI: 10.1039/B907932G
Citation: Org. Biomol. Chem., 2009,7, 4406-4414
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    Application of the Ugi four-component reaction to the synthesis of ditopic bifunctional chelating agents

    L. Tei, G. Gugliotta, S. Avedano, G. B. Giovenzana and M. Botta, Org. Biomol. Chem., 2009, 7, 4406
    DOI: 10.1039/B907932G

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