- A highly enantioselective synthesis of (R)-(-)-2-acetyl-5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthol. A key intermediate in the synthesis of anthracyclinones
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AB-Synthon (R)-(-)-5, a key intermediate in the asymmetric synthesis of anthracyclinones 3 and 4 is prepared in 35% overall yield and >95% ee. The key step involves hydroxylation of the potassium enolate of 7 using N-sulfonyloxaziridine (-)-6c.
- Davis,Kumar,Chen
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- Efficient enantioselective synthesis of (R)-2-acetyl-2-hydroxy-5,8-dimethoxy-1,2,3,4-tetrahydronaphthalene, the key intermediate in the synthesis of anthracycline antibiotics
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A simple, efficient, enantioselective synthesis of (R)-2-acetyl-2-hydroxy-5,8-dimethoxy-1,2,3,4-tetrahydronaphthalene, the key intermediate in the synthesis of anthracycline antibiotics, is described. The synthetic procedure starts with the Sharpless asymmetric dihydroxylation of 2-acetyl-5,8-dimethoxy-3,4-dihydronaphthalene: the diol obtained is regioselectively transformed into the corresponding chloroacetate which is dehalogenated and saponified to give the desired title compound in four steps with satisfactory yield (52%). No separation step is necessary at any point of the synthetic process. An efficient procedure for the synthesis of the starting enone and the stereoselectivity of the methanolysis of the intermediate chloroacetate are also reported.
- Badalassi, Fabrizio,Crotti, Paolo,Di Bugno, Cristina,D'Arata, Fabio,Favero, Lucilla,Ramacciotti, Alessio
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- A new stereocontrolled entry into the anthracyclinone families. Part 1: Synthesis of bicyclic precursors of 4-demethoxy-7-deoxy-derivatives
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A new and versatile strategy to obtain enantiomerically pure bicyclic precursors of compounds belonging to different anthracyclinone families is reported. Completely stereoselective hydrocyanation of (R)-4-(2,5-dimethoxyphenyl)-1-p-tolysulfinyl-2-butanone
- Garcia Ruano, Jose L.,Paredes, Cristina Garcia,Hamdouchi, Chafiq
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p. 2935 - 2944
(2007/10/03)
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- Remote control of dieis-alder additions. Enantioselective synthesis of (2r). 1,2,3,4-tetrahydro-2-hydroxy-5,8-dimethoxynaphthalen-2-yl methyl ketone (Wong's anthracycline intermediate) from furfural
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The enantiomerically pure (1S,4R,4'S,5'S)-1-(4',5'-dimethyl-dioxolan- 2'yl)-5,6-dimethylidene-7-oxabicyclo[2.2.1]hept-2-ene derived from the acetal of furfural and (2S,3S)-butane-2,3-diol underwent addition to 1-acetylvinyl para-nitrobenzoate in the prese
- Theurillat-Moritz, Viviane,Guidi, Antonio,Vogel, Pierre
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p. 3497 - 3501
(2007/10/03)
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- Short-step asymmetric syntheses of anthracycline antibiotics via enantioselective dihydroxylation by osmium tetroxide with a chiral diamine
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Short-step asymmetric syntheses of (+)-7-dehydroxy-4-demethoxydaunomycinone 4 and (-)-9-deacetyl-7-dehydroxy-4-demethoxy-9-hydroxymethyldaunomycinone 5 were accomplished via enantioselective dihydroxylation by osmium tetroxide with chiral diamine 13.
- Nakajima, Makoto,Tomioka, Kiyoshi,Koga, Kenji
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p. 10807 - 10816
(2007/10/02)
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- Novel Synthesis of Optically Pure Anthracyclinone Intermediates by the Use of Microbial Asymmetric Reduction with Fermenting Baker's Yeast
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Microbial reduction of the racemic α-hydroxy ketones ((+/-)-3a,b) with fermenting baker's yeast was found to afford diastereomeric mixtures of the vicinal-diols ((-)-4a,b) and ((+)-5a,b) in 90 and 91percent yields, respectively.Separation of these diastereomers was readily accomplished by fractional recrystallization, giving pure (-)-4a,b and mixtures of (-)-4a,b and (+)-5a,b.Oxidation of these samples furnished optically pure anthracyclinone intermediates ((R)-(-)-3a,b) and their partially optically active antipodes ((S)-(+)-3a,b).The undesired enantiomers ((S)-(+)-3a,b) and vicinal-diols((+)-5a,b) could be recycled to (+/-)-3a,b and the prochiral ketones (6a,c) by racemization with p-toluenesulfonic acid and oxidative cleavage with sodium metaperiodate, respectively.Another important optically pure anthracyclinone intermediate ((R)-(-)-3c) was prepared from (R)-(-)-3a,b according to the reported method.Keywords - α-hydroxy ketone; microbial reduction; anthracycline; optically pure anthracyclinone; 4-demethoxyanthracycline; optically pure 4-demethoxyanthracyclinone; baker's yeast; oxidation; racemization; vicinal-diol
- Tamoto, Katsumi,Terashima, Shiro
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p. 4328 - 4339
(2007/10/02)
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- A Stereoconvergent Synthesis of (+)-4-Demethoxydaunomycin
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Sharpless kinetic asymmetric epoxidation on (+/-)-2-(1-hydroxyethyl)-5,8-dimethoxy-3,4-dihydronaphthalene followed by LiAlH4 reduction gave R-(-)-2-(S-1-hydroxyethyl)-2-hydroxy-5,8-dimethoxy-1,2,3,4-tetrahydronaphthalene and the undesired antipode: the former was converted into R-(-)-2-acetyl-2-hydroxy-5,8-dimethoxy-1,2,3,4-tetrahydronaphthalene while the latter was epimerized and recycled.
- Rao, A. V. Rama,Yadav, J. S.,Reddy, K. Bal,Mehendale, A. R.
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p. 453 - 455
(2007/10/02)
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- Modified lithium aluminum hydrides
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Novel modified lithium aluminum hydride type reducing agents obtained by reacting one equivalent of lithium aluminum hydride with one equivalent of an optically active N-substituted ephedrine of the formula, STR1 (wherein R 1 is a C 1 -C 4 alkyl group or benzyl group, and Ph is phenyl group)and two equivalents of an N-substituted aniline of the formula, STR2 (wherein R 2 is C 1 -C 4 alkyl group or phenyl group, and Ph is phenyl group).This reducing agent is usable for reducing the organic compounds having a carbonyl group (ketone group or aldehyde group) in their structure into the corresponding alcohols. It is particularly useful as a reducing agent for asymmetrically reducing the unsymmetrical ketones to selectively produce either an alcohol in which the asymmetric carbon atom bonded to the hydroxy group is in R-configuration or an alcohol in which said asymmetric carbon atom is in S-configuration.
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- AN EFFICIENT SYNTHESIS OF OPTICALLY PURE ANTHRACYCLINONE INTERMEDIATES BY THE NOVEL USE OF MICROBIAL REDUCTION
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Reduction of the racemic α-hydroxy ketones((+/-)-3a,b) with fermenting baker's yeast followed by fractional recrystallization and oxidation was found to readily afford optically pure anthracyclinone intermediates((R)(-)-3a,b) and their partially optically active antipodes((S)(+)-3a,b).The useless enantiomers((S)(+)-3a,b) and diastereomeric vicinal-diols((+)-5a,b) could be recycled to (+/-)-3a,b and the achiral ketones(6a,b) by racemization and oxidative cleavage, respectively.
- Terashima, Shiro,Tamoto, Katsumi
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p. 3715 - 3718
(2007/10/02)
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- A SIMPLE SYNTHESIS OF (+/-) 4-DEMETHOXYDAUNOMYCINONE
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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.
- Rao, Rama A. V.,Deshpande, V. H.,Reddy, Laxma N.
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p. 2661 - 2664
(2007/10/02)
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