Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Patent
1993-03-17
1995-06-13
Robinson, Douglas W.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
536 111, 536119, 536120, 552208, 552261, 552262, 552268, 552290, C08B 3700, C09B 100
Patent
active
054244218
DESCRIPTION:
BRIEF SUMMARY
This invention relates to the synthesis of carminic acid (7-.beta.-D-glucopyranosyl-1-methyl-3,5,6,8-tetrahydroxyanthra-9,10-quinon e-2-carboxylic acid) and principal intermediates; alkyl 6-deoxykermesates (alkyl 3,5,8-trihydroxy-1-methyl-9,10-anthraquinone-2-carboxylates) and 6-deoxycarminic acid.
The hydroxyanthraquinone structure is common to a number of antibiotics such as carminomycin and to the natural colouring material carminic acid ##STR1## which is the 7-.beta.-(D)glucosyl derivative of kermesic acid. ##STR2##
Carminic acid,the colourant principle of cochineal, is extracted from the dried female bodies of the insect species Dactylopius coccus Costa which feed on the wild cactus Nopalla coccinellifera. The natural supply is variable and subject to large price fluctuations, and therefore it is desirable to produce carminic acid by synthetic means Kermesic acid is obtained from Kermes illicis.
The present invention provides intermediates for the synthesis of kermesic acid and carminic acid.
The invention comprises, in one aspect, the synthesis of alkyl 6-deoxykermesates by reaction of a 2-halogenonaphthazarin (2-halogeno-5,8-dihydroxy-1,4-naphthoquinone) with a bis-trimethylsilyl-diene (bis-TMS-diene). 2-Halogenonaphthazarin dimethyl ether or diacetate may be used. Throughout the specification the term "alkyl" is to be understood to include a "benzyl" group.
The 2-halogenonanphthazarin may be 2-chloronaphthazarin.
A Friedel-Crafts reaction may be used to synthesize 2-chloronaphthazarin or chlorine may be added to naphthazarin to give the adduct, 2,3-dichloronaphthazarin followed by dehydrochlorination.
The Friedel-Crafts reaction may be effected either through the reaction of 2-chloromaleic anhydride with hydroquinone or from 2-chlorohydroquinone and maleic anhydride, and an aluminium chloride/sodium chloride melt.
A 2,3-dichloro adduct of naphthazarin may be used in place of the 2-chloronaphthazarin since it loses hydrogen chloride in the heating of the toluene reaction medium. Also, the dimethyl ether or the diacetate of 2-chloronaphthazarin, or 2-bromonaphthazarin can be used with advantage in the reaction. These derivatives may be prepared by methylation or by acetylation by a number of different procedures.
Alternatively, 2-chloronaphthazarin dimethylether may be synthesised by the Diels-Alder reaction of 1,1,4-trimethoxybuta-1,3-diene with 2,6-dichlorobenzo-1,4-quinone.
Naphthazarin itself could be used in the reaction, but it is considerably slower to react, and the working-up is complicated by a number of inseparable impurities.
The invention comprises in another aspect the synthesis of 6-deoxykermesic acid (3,5,8-trihydroxy-1-methyl-9,10-anthraquinone-2-carboxylic acid) by demethylation of the reaction products of methylated cochinellic anhydride with 1,4-dimethoxybenzene by a Friedel-Crafts reaction.
The Friedel-Crafts reaction may be catalysed by BF.sub.3 etherate or aluminium chloride/sodium chloride.
The methylated cochinellic anyhydride may be prepared by first reacting a `bis-TMS-diene` by Diels-Alder addition with a halogenomaleic anhydride (chloro- or bromo-), followed by methylation of the 5-hydroxyl group. Methyl, ethyl and benzyl members of the bis-TMS-diene series may be used. The reaction may be carried out in refluxing toluene solution.
The bis-TMS-diene (alkyl 1-methyl-1,3-bis (trimethylsilyl)-1,3-butadiene-2-carboxylate) may be prepared from an alkyl diacetylacetate by reacting it with trimethylsilyl chloride in the presence of triethylamine in dry solvent. However, other silylating agents include O,N bis-trimethylsilylacetamide and hexamethyldisilazane, the former yielding a mixture of the cis/trans forms, the latter yielding the trans form only.
The invention comprises in another aspect, the synthesis of alkyl 6-deoxykermesate trimethyl ether by methylation of alkyl 6-deoxykermesate in acetone containing K.sub.2 CO.sub.3 and methylating agent.
From this product, an alkyl 3,5,8,9,10-pentamethyoxy-1-methylanthracen-2-carboxylate is synthesised by reductive permethylation (Na
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Fiecchi, deceased Alberto
Tyman John H. P.
European Colour PLC
Fonda Kathleen Kahler
Robinson Douglas W.
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