Can. J. Chem. 62, 2845 (1984).The redox behavior of daunombicin and its analogues has been studied by differential pulse polarography (DPP) in phosphate-buffered (pH 7. I) solutions at 37.S"'. 'The reductive deglycosidation reaction has been found to be under stereoelectronic control as the conformation of the alicyclic ring strongly affects the kinetics of the sugar moiety detachment. The substitution pattern of the anthraquinone system and/or the cyclohexene ring may determine the shape of the latter and in turn the stability of the glycosidic bond. We observe that while daunorubicin, 4-demethoxy-l I-deoxydaunorubicin, and 10(R)-methoxydaunorubicin easily eliminate L-daunosamine upon polarographic reduction yielding the corresponding 7-deoxyaglycones, 4-demethoxy-6-deoxydaunombicin and 10(S)-methoxydaunorubicin are stable towards deglycosidation. There is a pronounced stereoelectronic effect which results in a faster cleavage of those glycosidic bonds which have a relatively small dihedral angle with respect to the T-type orbital(s) of the anthraquinone system. Among the aglycones, the 10(S)-acetoxy and 10(R)-azidodaunomycinones are reductively converted to daunomycinone whereas the 10(R)-and 10(S)-methoxydaunomycinones do not undergo splitting of either the benzylic CIO-OCH, or the C 7 4 H bond.VINCENZO MALATESTA, SERGIO PENCO, NEREO SACCHI, LUIGI VALENTINI, ARISTIDE VIGEVANI, et FEDERICO ARCAMONE.Can. J. Chem. 62, 2845 (1984).Faisant appel a la polarographie pulsCe diffkrentielle (PPD) et opkrant a 37,S°C, dans des solutions tampons de phosphate (pH 7,1), on a CtudiC le comportement redox de la daunorubicine et de ses analogues. On a trouvC que la reaction de dCglycosidation riductrice se produit sous contrble stt5rCoClectronique puisque la conformation du cycle alicyclique influence fortement la cinCtique de la dissociation du sucre. Les divers types de substitution sur le systkme anthraquinone et/ou sur le cyclohexkne peuvent Cventuellement dkterminer la forme de ce dernier et, par voie de consCquence, la stabilitC du lien glycosidique. Alors que la reduction polarographique de la daunorubicine, de la dCmCthoxy-4 dCoxy-l 1 daunorubicine et de la mtthoxy-10(R) daunombicine provoque une elimination facile de la L-daunosamine conduisant aux dCoxy-7 aglycones correspondantes', la dCmtthoxy-4 dCoxy-6 daunorubicine et la mCthoxy-IO(S) daunorubicine sont stables vis a vis de la pairs of the DNA (3-8) has been proposed as a prerequisite in the mechanism of biological action of this class of antibiotics, Furthermore, the involvement of a free radical intermediate the real possibility exists for covalent binding to other parts of in the metabolism by mammalian microsomes of the anthrathe cell besides the intercalative region of stacked base-pairs. The same electronic features that render the anthracyclines molecules particularly suited for intercalation with DNA bases allow them to act as very efficient electron acceptors. Thus the anthracyclines can be activated in biochemical systems via enzyme mediated redox proc...
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