Hydrophilic Derivatives of Dithranol

Abstract

The syntheses of dithranol derivatives with co-carboxyalkyl side chains at C-2 (and C-7) or co-methoxycarbonylacyl-substituents at C-10, respectively, are described. Hydrophile DithranolderivateDie Herstellung von Dithranolderivaten mit co-Carboxyalkyl-Seitenketten an C-2 (und C-7) bzw. mit co-Methoxycarbonylacyl-Substituenten an C-10 wird beschrieben.We have reported a) upon the inhibition of glucose-6-phosphate-dehydrogenase by dithranol (l) 1 ), b) upon the UV-spectra of 1 and its anion 2 ) and c) upon the active oxygen species generated by l-C-10-anion 3 ). These experiments were hampered by the low degree of solubility of 1 in aqueous buffer systems.Here we describe the syntheses of hydrophilic derivatives of 1 which will be used as model compounds for further experiments in the context of the problems a)-c) mentioned above. B) C-2 (and C-7) Substituted Dithranol Derivatives2-(2-carboxyethyl)-dithranol 7 was obtained by ether cleavage, saponification, decarboxylation, and reduction of the anthraquinone 8 6) with SnCl 2 in a one-pot-reaction according to AuterhoffX Chrysazin (9) when being treated with an excess of (HO) 2 CH-COOH/NaOH/Na-dithionite according to Marschalk® yielded thebis-(carboxymethyl)-dihydroxyanthraquinone 10 as a very polar, crude material which was methylated to 11 for characterization. Under Auterhoffs reductive conditions^ 11 was converted to 2,7-bis-(carboxymethyl)-dithranol 12.Analogously to the reaction of chrysazin (9) its mono-methyl ether 13 6) was converted with (HO) 2 CH-COOH to the mono-carboxymethyl-derivative 14, which was reduced to the carboxymethyldithranol 15 with concomittant ether cleavage. A) C-10-Acylated Dithranol DerivativesC-10-acylated derivatives of 1 have been investigated thoroughly by Mustakallio et al. 4) mainly under clinical aspects, butantrone (2) being the most potent compound of this series. Unfortunately 2 is not suitable for our purposes. So we converted 1 into the esters 3 and 4, respectively, by acylation with co-methoxycarbonyl-propionyl chloride 5) or the homologous co-methoxycarbonyl-butyryl chloride.Besides the main components 3 and 4 the phenyl ester 5 arose as a side product. -1 reacted with succinyl chloride yielding the lactone 6.

The structure of ActVA-Orf6, a novel type of monooxygenase involved in actinorhodin biosynthesis

“…Soaking times are reported in Table I. Acetyl dithranol has been synthesized according to Tanzer et al . (1988).…”

Anthralin derivatives—inhibition of 5‐lipoxygenase—antipsoriatic efficacy

“…Anthralin 8) (1); l-acetoxy-9-anthrone 9) (2); l,8-diacetoxy-9-anthrone 10) (3); l-hydroxy-8-methoxy-9-anthrone n) (4); l,8-dimethoxy-9-anthrone n) (5); l-amino-9-anthrone 12) (6) from 1-amino-anthraquinone (Aldrich); 1-hydroxy-9-anthrone 13) (7); 9-anthrone (8) (Janssen); l,8-dichloro-9-anthrone 14) (9); benzophenone (10) (Merck); 2,2'-dihydroxybenzophenone (11) (EGA-Chemie); (9,10-dihydro-1,8-dihydroxy-9-oxo-anthracen-2-yl)-acetic acid 15 Partition coefficients were determined by a HPLC method 25,26,27 *. Stationary phase: Nucleosil 100 C18 7-u.M; mobile phase: methanol/ water/acetic acid (77:23:0.1 by vol., pH 5.5); flow rate: 1 ml/min; standards: benzoic acid, benzophenone, naphthalene, anthracene, 1,8-diacetoxy-9-anthrone.…”

Antipsoriatic Anthrones with Modulated Redox Properties. 4. Synthesis and Biological Activity of Novel 9,10-Dihydro-1,8-dihydroxy-9-oxo-2- anthracenecarboxylic and -hydroxamic Acids

“…Anthracenone acetic and propionic acids 4a and 5a were prepared as previously described which was esterified ( 25 ) and protected as the methyl ether 26 , alkylated with the appropriate bromides ( 27 − 30 ), and then reduced (Scheme ) 5 …”

“…Anthracenone acetic and propionic acids 4a and 5a were prepared as previously described. 30 2-Propionic acids 9a-11a were prepared from 24, 30 which was esterified (25) and protected as the methyl ether 26, alkylated with the appropriate bromides (27)(28)(29)(30), and then reduced (Scheme 5). 28 The benzyl-linked acid 13a was recently described, 31 and the benzoyl-linked acid 14a was prepared as illustrated in Scheme 6.…”