Naphthazarin Derivatives Research Articles

ChemInform Abstract: The Chemistry of Naphthazarin Derivatives. Part 3. Synthesis of the Dideoxy Analogue of Islandoquinone.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Chemistry of Naphthazarin Derivatives. Part 4. A Simple Preparative Synthesis of Mompain (II)

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Naphthazarin derivatives (II) 1: Formation of glutathione conjugate, inhibition of DNA topoisomerase-I and cytotoxicity

6-(1-Hydroxyalkyl)-5,8-dimethoxy-1,4-naphthoquinones, expressing a higher reactivity in conjugation with glutathione, showed a greater potency in the inhibition of DNA topoisomerase-I and the cytotoxicity against L1210 cells than 2-(1-hydroxyalkyl)-DMNQ derivatives, implying the participation of electrophilic arylation in the bioactivities. In further study 6-(1-Hydroxyalkyl)-5,8-dimethoxy-1,4-naphthoquinones with an alkyl group of shorter chain length (C 2 ∼ C 6) exerted a greater bioactivities than those with longer chain length(>C 6).

Hybocarpone, a novel cytotoxic naphthazarin derivative from mycobiont cultures of the lichen Lecanora hybocarpa

Hybocarpone ( 1), a novel pentacyclic naphthazarin-derived dimer has been isolated from mycobiont cultures derived from the lichen Lecanora hybocarpa. The structure of hybocarpone ( 1) was established on the basis of 1D and 2D NMR spectroscopy. Its relative stereochemistry was predicted with the use of molecular modelling and confirmed by X-ray crystallographic analysis. Hybocarpone ( 1) was found to be a potent cytotoxin (IC 50 c 0.27 μM), active against the murine P815 mastocytoma cell line.

The chemistry of naphthazarin derivatives

Direct oxidation of naphthazarin with manganese dioxide in conc. H2SO4 was found to be a simple and effective method for the synthesis of mompain.

The chemistry of naphthazarin derivatives

The chemistry of naphthazarin derivatives

Naphthazarin derivatives: synthesis, cytotoxic mechanism and evaluation of antitumor activity.

The rate of the GSH conjugate formation, the inhibition of DNA topoisomerase-I and the cytotoxic activity against L1210 cells of the naphthoquinones showed the same order; 5,8-dimethoxy-1,4-naphthoquinone (DMNQ) > 6-(1-hydroxyethyl)-DMNQ > 2-(1-hydroxyethyl)-DMNQ; the steric hindrance of the substituents, particularly 2-substutuent, in reacting with cellular nucleophiles must be the main cause for lowering the bioactivities. Acetylation of 2-(1-hydroxyethyl)-DMNQ producing 2-(acetyloxyethyl)-DMNQ potentiated the bioactivities; 2-(1-hydroxyethyl)-DMNQ did not react with GSH and the enzyme, and showed ED50 of 0.680 microgram/ml, whereas the values of 2-(1-acetyloxyethyl)-DMNQ were the conjugate formation of 0.14 microM, IC50 value of 81 microM for the enzyme inhibition and ED50 of 0.146 microgram/ml for the cytotoxcity. Furthermore, the acetylation 2-(1-hydroxyethyl)-DMNQ (T/C, 119%) enhanced the T/C values for the mice bearing S-180 tumor [T/C of 2-(1-acetyloxyethyl)-DMNQ, 276%]. It was assumed that the difference in bioactivities ensued by acetylation was based on the mechanism of the so-called bioreductive alkylation.

Chemistry and hair dyes application of dihydroxy derivatives of anthraquinone and naphthoquinone

Leucoquinizarin reacted with butylamine to give 1-butylamino-4-hydroxyanthraquinone and 1,4-bis(butylamino)anthraquinone. Their structures were elucidated and the reaction mechanism was discussed from the kinetic studies. Quinizarin reacted with butylamine to give 2-butylaminoquinizarin selectively, even in the presence of sodium dithionite. Under a nitrogen atmosphere, quinizarin was butylaminated to give 1-butylamino-4-hydroxyanthraquinone and/or 1,4-bis(butylamino)anthraquinone, even in the absence of sodium dithionite. Effects of sodium dithionite, solvent, and reaction atmosphere were examined and the animation mechanism was also discussed. The structures of leuco compounds of naphthazarin, its butylamino derivatives were clarified and the amination mechanism was also discussed. Leuconaphthazarin dyed wool and human hair in water without any oxidants at 30 °C to give reddish purple and an addition of benzyl alcohol accelerated the dyeing, which did not remove at all, even in 25% pyridine solution under refluxing conditions. The chemical interaction between naphthazarin and keratin was proposed from Raman and microphotomeric spectra. Leuco-2-butylaminonaphthazarin dyed wool and human hair in the presence of ammonia. On the other hand, the dyeabilities of leuco compounds of quinizarin, 1-butylamino-4-hydroxyanthraquinone and 1,4-bis(butylamino)anthraquinone was quite low compared to naphthazarin derivatives. This method which utilize isolable leuco compounds is the first attempt for dyeing wool and human hair.

2-Substituted naphthazarins; synthesis and antitumor activity.

A series of 2-substituted naphthazarin derivatives, 5,8-dihydroxy-1,4-naphthoquinone (DHNQ) derivatives and 5,8-dimethoxy-1,4-naphthoquinone (DMNQ) derivatives, were synthesized, and their cytotoxic activity against some cancer cell lines and antitumor action against S-180 tumor were evaluated. In general, 2-(1-hydroxyalkyl)-DHNQ derivatives showed a higher cytotoxicity than 2-(1-hydroxyalkyl)-DMNQ derivatives, implying a predominant role of redox cycling rather than electrophilicity in cytotoxicity. 2-(1-Alkoxy-4-methylpentyl) or 2-(1-acyloxy-4-methylpentyl) derivatives were produced by alkylation or acylation at the C-1' position of 2-(1-hydroxy-4-methylpentyl)-DHNQ or DMNQ derivatives. Although the cytotoxicity differed according to the size of the alkyl or acyl chain, alkylation or acylation at the C-1' position did not improve the cytotoxicity remarkably, and DHNQ derivatives were still more cytotoxic than DMNQ derivatives. Separately, in vivo testing showed that 2-(1-acyloxyalkyl)-DHNQ derivatives or 2-(1-alkoxyalkyl)-DHNQ derivatives expressed a higher antitumor action than 2-(1-hydroxyalkyl)-DMNQ or -DHNQ derivatives in contrast to the cytotoxicity observations. The total size of two side chains at C-1' seemed to govern the antitumor activity, with 9 to 11 carbon atoms being optimal. Thus, it is suggested that the physical properties as well as the chemical reactivity are to be considered in relation to the antitumor action of 2-substituted naphthazarin compounds.

Naphthazarin derivatives from cultures of the lichen Cladonia cristatella

High pigment-producing cell aggregates of the cultured spore-derived mycobiont of a lichen, Cladonia cristatella, were isolated by clonal selection. The new naphthazarin derivatives, cristazarin (3-ethyl-2-hydroxy-7-methoxynaphthazarin) and 6-methylcristazarin, were identified as red pigments from the liquid culture. A depside, barbatic acid, was also detected in C. cristatella and Acarospora fuscata mycobiont liquid cultures.

Acylated saponins from Crocosmia plants.

Most saponins obtained from monocotyledonous plants are steroidal saponins and triterpenoid saponins are rarely found. The class of Iridaceae belongs to the monocotyledon. Family Gladioleae plants (Iridaceae) are widely cultivated as garden plants. In the course of studies on saponins in the Gladioleae, nineteen novel triterpenoid saponins were isolated from the corms of Crocosmia crocosmiiflora and C. masoniorum. Montbretia (C. crocosmiiflora N.E.Br.) belonging to the Gladioleae is cultivated on the garden. Several phytochemical investigations of C. crocosmiiflora have been undertaken. An antimicrobial naphthazarin derivative has been isolated by Masuda et al.1 Furthermore, it has been reported that the hot water extract of its corms shows antitumor activity and the antitumor active principle is a mixture of saponins.2

Positional Assignments of a Substituent Group of 3-Substituted Juglones by the Off-Resonance 13C NMR Spectra

Abstract Taking into account the fact that the long-range 13C–1H coupling constant 3JCH is greater than 2JCH, positional assignments of a substituent group of 3-substituted juglones were easily accomplished by off-resonance 13C NMR spectra using a 60-MHz instrument for 1H. This method was applicable to a structural determination of naphthazarin derivatives.

A Novel Synthesis of Naphthazarin and Juglone Derivatives by Reaction of Naphthazarin and Juglone with Cyclic Enol Ethers

Abstract The reaction of naphthazarin with cyclic enol ethers in acetic acid in the presence of BF3·OEt2 gave naphthazarin derivatives such as cycloshikonin, having a cyclic ether substituent, in one step. Cyclic enol ethers did not attack the quinone ring of naphthazarin but the benzene ring, and the corresponding naphthazarin derivatives were produced after tautomerization. This reaction was applicable to juglone to give juglone derivatives bearing a cyclic ether substituent.

Successive Michael Reaction-Sigmatropic Rearrangement of Naphthodiquinone with O-Silylated Ketene Acetals Leading to Synthesis of Cycloshikonin and Structure-Reactivity Relationship for Side Chain of Naphthazarins.

Synthesis of cycloshikonin via successive Michael reaction-sigmatropic rearrangement of naphthodiquinone with O-silylated ketene acetals is described. The structure dependence of the reactivity of the side chain of intermediary naphthazarin derivatives has also been investigated.

Constituents of Tritonia crocosmaeflora, I. Tricrozarin A, a novel antimicrobial naphthazarin derivative.

A novel naphthazarin derivative, tricrozarin A, has been isolated from the fresh bulbs of Tritonia crocosmaeflora and was characterized as 5,8-dihydroxy-2,3-dimethoxy-6,7-methylenedioxy-1,4-naphthoquinone (2,3-dimethoxy-6,7-methylenedioxynaphthazarin). Tricrozarin A exhibits antimicrobial activity against gram-positive bacteria, fungi, and yeast in vitro and is the first tetra-oxygenated naphthazarin derivative isolated from higher plants.

In situ electron spin resonance spectroscopy studies of electrode processes

The usefulness of ESR spectroscopy for studying electrode processes is discussed and then illustrated by two selected examples. The first one deals with the identification of a radical intermediate in the electroreduction of some naphthazarin derivatives. The second example shows the possibility of elucidating the mechanism of electron exchange inside an electrode material, such as M 2 P 2 S 6 , during its electroreduction with simultaneous intercalation of lithium ions.

In situ electron spin resonance spectroscopy studies of electrode processes

The usefulness of ESR spectroscopy for studying electrode processes is discussed and then illustrated by two selected examples. The first one deals with the identification of a radical intermediate in the electroreduction of some naphthazarin derivatives. The second example shows the possibility of elucidating the mechanism of electron exchange inside an electrode material, such as M 2P 2S 6, during its electroreduction with simultaneous intercalation of lithium ions.

Regiospecific synthesis of quinizarin and naphthazarin derivatives by cycloaddition

The diene (E)-1,1,4-trimethoxybuta-1,3-diene underwent regiospecific cycloaddition to derivatives of 2(3)-chloro-1,4-naphthoquinone. The resulting adducts were aromatized to give 1,4-dioxygenated anthraquinones. The latter were obtained as derivatives of quinizarin dimethyl ether or of quinizarin monomethyl ether depending on the conditions of aromatization. Cycloaddition of the diene to non-halogenated naphthoquinones proceeded similarly, orientation being controlled by substituents in the benzenoid ring. Analogous reaction of the diene with benzoquinones gave 5,8-dioxygenated naphthoquinones (naphthazarins), generally in limited yield. The procedure has been applied to synthesis of the mould metabolites helminthosporin and cynodontin.

In situ electrochemical reduction of some naphthazarin derivatives. An electron spin resonance and INDO study

Twelve naphthazarin derivatives were reduced electrochemically giving rise to the corresponding semiquinone anion radicals. Their e.s.r. spectra were recorded in situ and their hyperfine coupling constants and g factor were evaluated. For this purpose, SCF INDO MO calculations were performed in order to obtain an approximate value of the different coupling constants. The structure of these radicals was also deduced from these calculations, showing a strong linear O–H–O hydrogen bond, free rotation of the methyl group, and the absence of hyperfine interactions in the methoxy-group.

Polycyclic hydroxyquinones—VIII: Preparation of acetylhydroxynaphthazarins by photo-fries rearrangement. A convenient synthesis of spinochrome A

Several synthetic routes to mono- and dihydroxynaphthazarins bearing an acetyl side-chain have been explored. Methoxynaphthazarin 1 has always been the starting material. Acylation is brought about via a photo-Fries rearrangement of various adequately substituted acetoxynaphthalenes prepared in several steps from 1. Further steps including oxidative demethylation, hydrolysis and ether cleavage reactions, led to the desired mono- and dihydroxysubstituted acetylnaphthazarins. A new synthesis of Spinochrome A 24, a natural occurring pigment representative of this kind of naphthazarin derivatives, is described.