Tautomeric instability of 10-deoxydaunomycinone hydroquinone

Brand, David J.; Fisher, Jed F.

doi:10.1021/ja00271a045

Cited by 21 publications

(7 citation statements)

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“…System (3) was obtained by either electrochemical reduction of 5-iminodaunorubicin 6 or treatment of 7-deoxydaunorubicinone (5) with sodium dithionite. 7 In other work, hydrogenolysis of daunorubicinone (6) (palladium on barium sulfate) gave a product whose reported spectra also appear to correlate with the 5,7-bisdeoxy system (3); this is in preference to the isomeric 7,11-bisdeoxy structure originally suggested. 8 While the present investigation was in progress, the same 5,7-deoxy chromophore was obtained as its 13-ol (7), by reduction of (5) with sodium borohydride, together with its 7,12-bisdeoxy analogue (8).…”

Section: Introductionmentioning

confidence: 82%

“…Thus reduction of the aglycone (6) under those same conditions gave only the 7-deoxygenated products (3), (4) and (7). In contrast, the products from parallel reductions of (1) were largely glycosides (12) and (13), and no 12-deoxygenated product analogous to (4) was observed, within the limits of 1 H n.m.r.…”

Section: -Deoxy Anthracyclinesmentioning

confidence: 90%

“…mass spectra. The change of catalyst from palladium to platinum thus afforded preferential deoxygenation at position 5 over 7 for the first time, albeit accompanied by competitive reduction at position 13. By contrast, parallel platinum-catalysed hydrogenation of the unprotected aglycone (6) gave 5,7-bisdeoxydaunorubicinone (3), together with trace amounts of (4) and (7). While retention of the 7-oxy substituent during reduction of (9) may reflect its cyclic nature, it also seemed possible that the difference may have derived from the steric bulk of the phenylboronate residue.…”

Section: -Deoxy Anthracyclinesmentioning

confidence: 99%

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5-Deoxy, 12-Deoxy, 5,12-Bisdeoxy, and 4,5,12-Trisdeoxy Anthracyclines: Synthesis of New Analogues of Daunorubicin and Doxorubicin by Controlled Deoxygenation of the C-Ring.

Cameron¹,

Feutrill²,

Griffiths³

2000

Aust. J. Chem.

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Hydrogenation of the anthracyclines daunorubicin (1) and doxorubicin (2) gave selective deoxygenation at position 5. Hydride reduction of (1) and (2) gave complementary regiocontrol, leading to 12-deoxygenation or 5,12- bisdeoxygenation. This chemistry allows retention of the 7-glycoside and the side-chain carbonyl groups. It has led to new anthracycline families possessing all of the stereochemical and most of the spatial characteristics of the parent compounds (1) and (2). These are typified by 5-deoxy (12), (15); 12-deoxy (22), (23); 5,12-bisdeoxy (34), (35); and 4,5,12-trisdeoxy systems (36). All possess high anticancer activity.

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Section: Introductionmentioning

confidence: 82%

Section: -Deoxy Anthracyclinesmentioning

confidence: 90%

Section: -Deoxy Anthracyclinesmentioning

confidence: 99%

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5-Deoxy, 12-Deoxy, 5,12-Bisdeoxy, and 4,5,12-Trisdeoxy Anthracyclines: Synthesis of New Analogues of Daunorubicin and Doxorubicin by Controlled Deoxygenation of the C-Ring.

Cameron¹,

Feutrill²,

Griffiths³

2000

Aust. J. Chem.

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“…These stereoisomers now bear the common name leucodaunomycin (37) because they are less colored than daunomycin. The process of tautomerization of the hydroquinone state was first observed in the reduction of 7-deoxydaunomycin to its hydroquinone (77). Leucodaunomycin is characterized by twin visible absorption bands at 420 and 440 nm.…”

Section: Formation Of Leucodaunomycin a Semistable Form Of Daunomycin...mentioning

confidence: 99%

Redox chemistry of anthracycline antitumor drugs and use of captodative radicals as tools for its elucidation and control

Gaudiano¹,

Koch²

1991

Chem. Res. Toxicol.

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The oxomorpholinyl radicals are unique materials in organic and medicinal chemistry. Their closest parallel lies in inorganic chemistry with dithionite, which exists in equilibrium with sulfur dioxide radical anion, also a one-electron reducing agent. However, dithionite is a more powerful reducing agent and is probably more toxic. The rate of release of the oxomorpholinyl radical from its dimer is medium and is structure dependent, which provides for some level of control. The oxomorpholinyl radicals TM-3 and DHM-3 are selective one-electron reducing agents for the anthracyclines, generating sequentially semiquinone and hydroquinone redox states. Formation of the reduced states of the anthracyclines is probably relevant to their cytotoxic activity. Semiquinones and hydroquinones react rapidly with molecular oxygen to yield superoxide. Hydroquinone redox states with anaerobic conditions in protic media at pH 7-8 undergo glycosidic cleavage to form quinone methides; in aprotic media or at pH less than 4, they tautomerize to leuco forms. Quinone methides react with protons from solvent to form 7-deoxyaglycons, with some nucleophiles to form adducts, and with molecular oxygen to form semiquinone methide. The reactivity of the quinone methide is a function of substitution; nucleophilic addition is facilitated by the absence of a hydroxyl group at the 11-position and by proper location of the nucleophile. Quinone methides and semiquinone methides are both viable transients for covalently linking anthracycline aglycons to biological macromolecules. DHM-3 dimer is of possible pharmaceutical value for the detoxification of quinone antitumor drugs and for the improvement of chemotherapy through modulating the redox chemistry of the quinone antitumor drugs.

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“…Several drugs need complexation to metal ions such as Fe 2þ , Fe 3þ , or Mg 2þ , present in enzymes. In several other cases, they mediate the cellular exchanges and modulate the transport, through the membrane, of Ca 2þ , Na þ and K þ ions [1][2][3][4][5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Organometallic complexes with biological molecules. XVIII. Alkyltin(IV) cephalexinate complexes: synthesis, solid state and solution phase investigations

Stefano

Scopelliti

Pellerito

et al. 2004

Journal of Inorganic Biochemistry

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Tautomeric instability of 10-deoxydaunomycinone hydroquinone

Cited by 21 publications

References 0 publications

5-Deoxy, 12-Deoxy, 5,12-Bisdeoxy, and 4,5,12-Trisdeoxy Anthracyclines: Synthesis of New Analogues of Daunorubicin and Doxorubicin by Controlled Deoxygenation of the C-Ring.

5-Deoxy, 12-Deoxy, 5,12-Bisdeoxy, and 4,5,12-Trisdeoxy Anthracyclines: Synthesis of New Analogues of Daunorubicin and Doxorubicin by Controlled Deoxygenation of the C-Ring.

Redox chemistry of anthracycline antitumor drugs and use of captodative radicals as tools for its elucidation and control

Organometallic complexes with biological molecules. XVIII. Alkyltin(IV) cephalexinate complexes: synthesis, solid state and solution phase investigations

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