32384-98-8Relevant academic research and scientific papers
An entry to the ring B:Ring C bishydroquinone leucodaunomycin series containing an intact carbohydrate
Sulikowski, Gary A.,Turos, Edward,Danishefsky, Samuel J.,Shulte, Gayle M.
, p. 1373 - 1377 (1991)
It has been found that diacetylation of the phenolic hydroxyl groups at C-6 and C-11 of daunomycin provides a product (see compound 12) that undergoes reduction of the ring C quinone to a hydroquinone without loss of the glycosyloxy function at C-7. Access to a stable heptaacetate (see compound 14) incorporating the nuclear bishydroquinone ensemble is thus provided. Basic hydrolysis of 14 accompanied by oxidation restores N-acetyldaunomycin. The success of this reaction reveals a surprising resistance to quinone methide formation via such leuco intermediates.
Design, synthesis and antitumor activities of novel 7-arylseleno-7-deoxydaunomycinone derivatives
Zhang, Shu-Jia,Jia, Zheng-Ping,Wang, Yan-Guang
, p. 3899 - 3904 (2002)
7-Arylseleno-7-deoxydaunomycinone derivatives 3a-e and 7-thiophenyl-7-deoxydaunomycinones (7 and 8) were synthesized and the antitumor activities of them were evaluated against human stomach cancer SGC-7901 and human leukaemia HL60. The cytotoxic assay sh
Tautomeric Instability of 10-Deoxydaunomycinone Hydroquionone
Brand, David J.,Fisher, Jed
, p. 3088 - 3096 (1986)
10-Deoxydaunomycinone and daunomycin are reduced by excess sodium dithionite, under anaerobic conditions, to 10-deoxydaunomycinone hydroquinone.This hydroquinone is not stable, having an approximate rate constant (in 48percent MeOH, 52percent H2O, 10 mM Tris-HCl, 10 mM Tris base) for its disappearance of 2E-4 s-1.This disappearance results from a number of tautomeric equilibria, which transform this hydroquinone into more stable species.Typically, eight products in addition to 10-deoxydaunomycinone are detected by reverse-phase liquid chromatographic analysis of the product mixture.Thus far seven of these products have been identified and characterized.Three of the products are diastereomers of (2R)-2-acetyl-1,2,3,4,4a,12a-hexahydro-2,6,11-trihydroxy-7-methoxy-5,12-naphthacenedione that have differing stereochemistry at the C-4a,C-12a ring juncture.The major diastereomer (50percent of the product) has a trans ring juncture, while the other two diastereomers (13percent and 5percent of the product) both have a cis ring juncture.Two of the product formed, (2R)-2-acetyl-1,2,3,4-tetrahydro-2,11-dihydroxy-7-methoxy-5,12-naphthacenedione (4percent of the product) and (2R)-2-acetyl-1,2,3,4-tetrahydro-2,6-dihydroxy-7-methoxy-5,12-naphthacenedione (2percent of the product), involve the loss of an oxygen from the anthracycline's C ring.The last two products, (8R)-8-acetyl-7,9,10,12-tetrahydro-6,8,11-trihydroxy-1-methoxy-5(8H)-naphthacenone (11percent of the product) and (9R)-9-acetyl-7,9,10,12-tetrahydro-6,9,11-trihydroxy-4-methoxy-5(8H)-naphthacenone (5percent of the product), are derived from the reduction of the dihydroxynaphthacenediones by the excess dithionite present in the mixture.The effect of Fe(III) ion chelation of the anthracycline on the anaerobic dithionite reduction of both daunomycin and 10-deoxydaunomycinone is examined.A modest rate increase for the tautomerization of the hydroquionone is observed for the anaerobic dithionite reduction of the 10-deoxydaunomycinone-Fe(III) chelate, whereas little effect is observed for the daunomycin-Fe(III) chelate.This surprising diversity of materials may account for the abundance of aglycon metabolites found in vivo (many as yet uncharacterized), may prove of value in the synthetic elaboration of anthracyclinones, and is likely to be representative of the hydroquinone behavior of the p-hydroxyanthracyclinones of the rhodomycinone, isorhodomycinone, and pyrromycinone families.
A facial synthesis of 7-selenodaunomycinone derivatives
Zhang, Shu Jia,Wang, Yan Guang
, p. 520 - 521 (2007/10/03)
7-selenodaunomycinone derivatives 3a-e were synthesised by condensation of daunomycinone 2 with aryl selenols catalysed by trifluoroacetic acid in dichloromethane at room temperature. When the concentration of aryl selenol exceeds 2 to 2-3 times, 7-deoxyd
Mechanistic studies of the reduction of daunomycin with sodium borohydride. Formation and reaction of borate esters
Schweitzer, Barbara Ann,Egholm, Michael,Koch, Tad H.
, p. 242 - 248 (2007/10/02)
Reduction of daunomycin with excess sodium borohydride in methanol degassed with prepurified nitrogen yielded 89% daunomycinol and 11% recovered daunomycin. Monitoring of the reaction by UV-vis spectroscopy revealed the formation of an intermediate with absorptions at 336 and 430 nm, which was assigned the borate ester structure 5 on the basis of the UV-vis absorption bands together with high-field 1H NMR, FTIR, and mass spectral data. Similar results were obtained upon reduction without nitrogen degassing. In contrast, sodium borohydride reduction under strictly anaerobic conditions, achieved with freeze-thaw degassing, predominantly yielded the products of glycosidic cleavage, 7-deoxydaunomycinol (6, 58%) along with daunomycinol (4, 17%). The sequential formation of two intermediates was observed: first, borate ester 5 and second, a longer lived intermediate with absorptions at 360 and 580 nm. The second intermediate is proposed to be 7-deoxydaunomycinol quinone methide borate ester (9) on the basis of the absorption bands, lifetime, and product structures compared with those observed upon reduction with the one-electron reducing agent, bi(3,5,5-trimethyl-2-oxomorpholin-3-yl) (TM-3 dimer). Reduction of 7-deoxydaunomycinone with excess sodium borohydride in nitrogen-degassed methanol yielded 42% 7-deoxydaunomycinol (6), 31% 5,7-dideoxydaunomycinol tautomer (1,2,3,4-tetrahydro-2,11-dihydroxy-2-(1-hydroxyethyl)-7-methoxy-5,12- naphthacenedione, 11), and 27% 7,12-dideoxydaunomycinol tautomer (1,2,3,4-tetrahydro-2,6-dihydroxy-2-(1-hydroxyethyl)-7-methoxy-5,12- naphthacenedione, 12). Again an intermediate with absorptions at 336 and 430 nm was observed, in this case, assigned to regioisomeric borate esters 13 and 14 on the basis of formation of regioisomeric dideoxydaunomycinol tautomers 11 and 12. The intermediacy of long-lived borate esters is relevant to the interpretation of studies employing sodium borohydride for the reductive activation of anthracyclines.
Reduction of daunomycin in dimethyl sulfoxide. Long-lived semiquinones and quinone methide and formation of an enolate at the 14-position via the quinone methide
Gaudiano, Giorgio,Frigerio, Massimo,Bravo, Pierfrancesco,Koch, Tad H.
, p. 3107 - 3113 (2007/10/02)
Anaerobic reduction of daunomycin (1, daunorubicin) in 5%/95% H2O/DMSO (DMSO = dimethyl sulfoxide) or in DMSO with sodium dithionite or bi(3,5,5-trimethyl-2-oxomorpholin-3-yl) (TM-3 dimer), respectively, yields 7-deoxydaunomycinone (7) and a mixture of the diastereomers of bi(7-deoxydaunomycinon-7-yl) (8). A precursor to both 7 and 8 is 7-deoxydaunomycinone quinone methide (4) formed from glycosidic cleavage of daunomycin hydroquinone (3). The hydroquinone 3 is estabished as a precursor to the quinone methide 4 from relative rates. In 5%/95% H2O/DMSO or DMSO, daunomycin semiquinone (2) and quinone methide (4) have much longer lifetimes than in 100% protic solvents such as H2O or methanol. The quinone methide reacts to form the side chain enolate most likely by intramolecular proton transfer from the methyl group at the 14-position to the 7-position.
Reactions radicalaires de la daunorubicine
Houee-Levin, C.
, p. 897 - 905 (2007/10/02)
Daunorubicine is an antitumor antibiotic activated in vivo by reduction.Its mechanism of action involves DNA and topoisomerase attack, but side effects are cytotoxicity related to free radical formation.Therefore the mechanism of the one-electron reduction of the drug and the reactions of the daunorubicin transients towards compounds of biological interest have been studied by the methods of radiolysis, in order to provide possible explanations of the drug mechanism of action.Their relative importance in cellular conditions is discussed.
