65529-77-3Relevant academic research and scientific papers
Synthetic Anthracyclinones, 36. - Convergent Synthesis of Enantiomerically Pure Daunomycinone Derivatives
Krohn, Karsten,Rieger, Hagen,Broser, Erwin,Schiess, Peter,Chen, Shizhi,Strubin, Thomas
, p. 943 - 948 (2007/10/02)
The ortho-quinoid vinylketenes 12 and 13 can be generated thermally or photochemically from the benzocyclobutenones 3 and 4.They undergo cycloaddition with the substituted benzoquinone 14 to yield the isomeric tetracyclic compounds 15, 16, 19, and 20 which can be oxidized to give the 10-deoxydaunomycinone derivatives 23 and 24.A similar cycloaddition of bisketenes obtained photolytically from the corresponding benzocyclobutenediones 9-11 with the enantiomerically pure AB building block 29 affords the symmetrically substituted daunomycinones 33-35 in only two steps.
Model Studies for an Asymmetric Synthesis of (+)-4-Demethoxydaunomycinone
Mehendale, A. R.,Kulkarni, Alpana,Nagarajan, Geeta
, p. 305 - 307 (2007/10/02)
2-Hydroxymethyl-5,8-dimethoxy-3,4-dihydronaphthalene (II) on t-butyl hydroperoxide oxidation followed by LAH reduction gives 2-hydroxy-2-hydroxymethyl-5,8-dimethoxy-1,2,3,4-tetrahydronaphthalene (IVa) in 85percent yield.The corresponding O-benzyl derivate (VI) on PDC oxidation affords 2-benzyloxy-5,8-dimethoxy-1,2,3,4-tetrahydronaphthyl-2-aldehyde (VII), which on Grignard reaction with methylmagnesium iodide followed by PDC oxidation affords the desired (+/-)-2-acetyl-2-O-benzyl-5,8-dimethoxy-1,2,3,4-tetrahydronaphthalene (IXa) in 70percent yield.Friedel-Crafts condensation of IXa with phthalic anhydride in the presence of AlCl3-NaCl melt furnishes (+/-)-4-demethoxy-7-deoxydaunomycinone (Ia) in 74percent yield, which on 7-hydroxylation affords the desired (+/-)-4-demethoxydaunomycinone (Ib) in 40percent yield.
Studies related to Anthracyclines. Part 2. Synthesis of (+/-)-4-Demethoxydaunomycinone
Gupta, Ramesh C.,Jackson, David A.,Stoodley, Richard J.,Williams, David J.
, p. 525 - 534 (2007/10/02)
A chromatography-free, six-step, diastereocontrolled synthesis of (+/-)-4-demethoxy-7-O-methyldaunomycine (3b) is described.The tetracyclic carbon skeleton is elaborated by a Diels-Alder strategy in which the 6a,7 and 10,10a bonds are constructed, the epoxytetraone (5) and the diene (10a) serving as precursors.Hydrolysis of the cycloadduct (11a) leads to the epoxypentaone (12a), the structure of which is confirmed by X-ray crystallography.The diastereocontrol is achieved in the reaction of the dihydroxytrione (13a) with ethynylmagnesium bromide or lithium acetylide, the reagents attacking the 9-carbonyl group from the face away from that bearing the 7-methoxy group to give the ethynyldione (14a).Although epimerisation of the dihydroxytrione (13a) at the 10a-position is a competing reaction when high concentrations of the metal acetylides are employed, the ethynyldione produced, i.e. (20), still possess the trans arrangement of the 7-methoxy and 9-ethynyl groups.The ethynyldiones (14a) and (20) are converted into compound (3b) by an oxidative isomerisation-hydration sequence.An attempt to effect the de-O-methylation of compound (3b), by the action of trimethylsilyl iodide, failed; a mixture of 4-demethoxy-7-deoxydaunomycinone (22b) and its 9-deoxy derivative (22a) resulted.The conversion of compound (3b) into the title compound (3a) is brought about by a trifluoroacetolysis-ammonolysis sequence.The conformation of the A ring of the anthracyclinones (3a) and (3b) and their precursors, as determined by high-field 1H n.m.r. spectroscopy, is discussed.
Total Synthesis of (+/-)-4-Demethoxydaunomycinone
Rao, A. V. Rama,Deshpande, V. H.,Sathaye, K. M.,Jaweed, S. M.
, p. 697 - 702 (2007/10/02)
2-Acetyl-5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthol (4), the key synthon for the total synthesis of various antitumor anthracyclinones, has been prepared either from 1,4-dimethoxynaphthalene and making use of metal-ammonia reduction or from benzoquinone and going through Diels-Alder reaction with 1,3-butadiene. 4 is then converted into (+/-)-4-demethoxydaunomycinone (3b).
Simple o-Quinodimethane Route to (+/-)-4-Demethoxydaunomycinone
Kerdesky, Francis A.,Ardecky, Robert J.,Lakshmikantham, M. V.,Cava, Michael P.
, p. 1992 - 1996 (2007/10/02)
The anthracycline antibiotics daunorubicin and adriamycin are important clinically useful drugs in the treatment of a number of human cancers.The structurally simplified synthetic analogues 4-demethoxydaunorubicin and 4-demethoxyadriamycin show much clinical promise.The synthesis of the corresponding aglycon (+/-)-4-demethoxydaunomycinone from the inexpensive dye intermediate quinizarin, utilizing o-quinodimethane intermediates, is discussed.
A SIMPLE SYNTHESIS OF (+/-) 4-DEMETHOXYDAUNOMYCINONE
Rao, Rama A. V.,Deshpande, V. H.,Reddy, Laxma N.
, p. 2661 - 2664 (2007/10/02)
A new and simple synthesis of 4-demethoxy-7-deoxydaunomycinone has been carried out essentially in three steps starting from 1,4-dimethoxy-6-tetralone.
