9,10-Anthracenedione

Diels-Alder Reaction. In 1928, Diels and Alder discovered that 1,3-unsaturated organic compounds reacted with quinoid systems to give partially hydrogenated, cycHc compounds. In the course of their work, they found that 1 mol of 1,4-naphthoquinone [130-15-4] reacted readily with 1 mol of 1,3-butadiene [106-99-0] to give a partially hydrogenated anthraquinone (11) l,4,4a,9a-tetrahydro-9,10-anthracenedione [56136-14-2] which, on oxidation with chromic oxide, produced anthraquinone (43) ... 

Emodine (l,3,8-trihydroxy-6-methyl-9,10-anthracenedione, archin) [518-82-1] M 270.2, m 253-257 , 255-256 , 256-257 , 262 , 264 (phenolic pKs 7—10). Forms orange needles from EtOH, Et20, C6H6, toluene or pyridine. It sublimes above 2(K)°at 12mm. [Tutin and Clewer J Chem... 

CN l,4-dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-9,10-anthracenedione dihydrochloride... 

Pharmacology and Mechanism of Action Mitoxantrone is an anthracenedione antineoplastic that is indicated for multiple sclerosis. The mechanisms of action thought to be important for MS are as follows ... 

This royal-blue-colored drug is an anthracenedione that inhibits DNA topoisomerase II. The pharmacokinetics of mitoxantrone may best be described by a three-compartment model, with an a half-life of 3 to 10 minutes, a 3 half life of 0.3 to 3 hours, and a median terminal half-life of 12 days. Biliary elimination appears to be the primary route of elimination, with less than 10% of the drug eliminated by the kidney.23 Mitoxantrone has shown clinical activity in the treatment of acute leukemias, breast and prostate cancer, and non-Hodgkin s lymphomas. Myelosuppression, mucositis, nausea and vomiting, and cardiac toxicity are side effects of this drug. The total cumulative dose limit is 160 mg/m2 for patients who have not received prior anthracycline or mediastinal radiation. Patients who have received prior doxorubicin or daunorubicin therapy should not receive a cumulative dose greater than 120 mg/m2 of mitoxantrone. Patients should be counseled that their urine will turn a blue-green color. 

The retro-Diels-Alder (RDA) reaction of anthracenedione (Eq 12.5) proceeds considerably faster in aqueous solution than in organic solvents.32 The addition of organic solvents to water retards the reaction, whereas glucose induces a modest acceleration. The results suggest that the origin of rate acceleration involves mainly enhanced hydrogen bonding of water to the activation complex for the RDA reaction. 

Of the various anthracenedione isomers, only the 9,10-compound is used for the synthesis of dyes it is usually referred to simply as anthraquinone (6.1). The parent compound is pale yellow in colour, having a weak absorption band in the visible region (n—>tt transition). The presence of one or more electron-donating substituents leads to significant bathochromic effects so that relatively simple derivatives are of commercial importance as dyes. The colour of such compounds, which usually contain amino or hydroxy groups, can be attributed to the existence of a charge-transfer absorption band [1]. 

The major class of topoisomerase I inhibitors comprise of the camptothecins, while topoisomerase II inhibitors fall into several classes - anthracyclines (e.g. doxorubicin), anthracenediones (mitoxantrone), anthrapyrazoles (bianthrazole), actinomycins (actinomycin D), acridines (m-AMSA), ellipticines (9-hydroxy-ellipticine) and epidophyllotoxins (Etoposide (VP-16) and VM-26). The chemical... 

Myocardial toxicity, manifested in its most severe form by potentially fatal CHF, may occur either during therapy with mitoxantrone or months to years after termination of therapy. Mitoxantrone use has been associated with cardiotoxicity this risk increases with cumulative dose. In cancer patients, the risk of symptomatic CHF was estimated to be 2.6% for patients receiving up to a cumulative dose of 140 mg/m. For this reason, monitor patients for evidence of cardiac toxicity and question them about symptoms of heart failure prior to initiation of treatment. Monitor patients with multiple sclerosis (MS) who reach a cumulative dose of 100 mg/m for evidence of cardiac toxicity prior to each subsequent dose. Ordinarily, patients with MS should not receive a cumulative dose greater than 140 mg/m. Active or dormant cardiovascular disease, prior or concomitant radiotherapy to the mediastinal/pericardial area, previous therapy with other anthracyclines or anthracenediones, or concomitant use of other cardiotoxic drugs may increase the risk of cardiac toxicity. Cardiac toxicity with mitoxantrone may occur at lower cumulative doses whether or not cardiac risk factors are present (see Warnings and Administration.and.Dosage). 

Copper-catalyzed reaction of guanidine with l,4-dichloro-9,10-anthracenedione 928 in DMF not only resulted in formation of the targeted 777-benzo[i ]perimidin-7-one ring system, but also resulted in substitution of the second chlorine atom by a dimethylamino group from the DMF solvent to give 929 <2002BMC1025>. 

Exercise 26-16 Reduction of 9,10-anthracenedione with tin and hydrochloric acid in ethanoic acid produces a solid, pale-yellow ketone (mp 156°), which has the formula C14H10O. This ketone is not soluble in cold alkali but does dissolve when heated with alkali. Acidification of cooled alkaline solutions of the ketone precipitates a brown-yellow isomer of the ketone (mp 120°), which gives a color with ferric chloride, couples with diazonium salts (Section 23-1OC), reacts with bromine, and slowly reverts to the isomeric ketone. 

Retro-Diels-Alder reactions of anthracenedione (51a) have been shown to proceed faster in aqueous solution than in organic solvents, apparently as a consequence of enhanced hydrogen bonding of water to the activated complex,30 since hydrophobic interactions with (51a) are of negligible importance. The results have been compared with previous kinetic data for bimolecular and intramolecular Diels-Alder reactions and the corresponding hydrogen bond and hydrophobic interactions have been discussed. 

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