V. F. Anufriev

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.

Simple preparative synthesis of spinochrome e, a pigment from sea urchins of the genus Echinothrix

A preparative synthesis of spinochrome E (2,3,5,6,7,8-hexahydroxy-1,4-naphthoquinone, 1), a metabolite of sea urchins of the genus Echinothrix, is proposed starting from 2,3-dichloro-6,7-diethoxynaphthazarine (4) with simultaneous substitution of the Cl atoms by hydroxyl- and nitro-groups, reduction of the latter, and subsequent removal of alkoxy groups and hydrolysis of the amine in the resulting 3-amino-2-hydroxy-6,7-diethoxynaphthazarine (6).

Chemistry of naphthazarine derivatives: XIV. Preparative synthesis of 1′-bromoalkylnaphthazarines

A reaction of alkylnaphthazarines with bromine in tetrachloromethane was investigated. A preparative synthesis was developed for substituted 1′-bromoalkylnaphthazarines, and based on the substance 1′-hydroxyalkylnaphthazarines were prepared, analogs of shikalkin, a racemic mixture of plant pigments from Boraginaceae family. 2-Acyl-3-hydroxynaphthazarine was synthesized, a minor metabolite of urchin from genus Echinothrix.

THE CHEMISTRY OF NAPHTHAZARIN DERIVATIVES. 3. SYNTHESIS OF THE DIDEOXY ANALOG OF ISLANDOQUINONE

The 7,7′-dideoxy analog of islandoquinone, binaphthazarin of a new structural type, bearing a 2-oxo-2,3-dihydro-1,4-naphthoquinone moiety was synthesized. The carbonyl group at the C(2) atom of this binaphthazarin easily adds water to give the correspondinggem-diol. Comparison of the spectral characteristics of the prepared diol and islandoquinone made it possible to elucidate more precisely the structure of the latter.

Synthesis of Spinochrome D, A Metabolite of Various Sea-Urchin Species

The sea-urchin metabolite spinochrome D (1) was synthesized in 58% overall yield via oxidation of 2,3-dichloronaphthazarin (13) into 2-hydroxy-6,7-dichloronaphthazarin (14), O-methylation of 14, nucleophilic substitution by MeO groups of the Cl atoms in the resulting 2-methoxy-6,7-dichloronaphthazarin (19), and hydrolysis of the obtained 2,3,6-trimethoxynaphthazarin (10).

Simple Synthesis of Spinochrome C, a Sea-Urchin Pigment

3-Acetyl-2,5,6,7,8-pentahydroxy-1,4-naphthoquinone (3-acetyl-2,6,7-trihydroxynaphthazarine, spinochrome C, 1a) is a sea-urchin (Class Echinoidea) metabolite [1]. Spinochrome C in addition to other classic quinoid pigments from this animal class is a potent antioxidant [2]. Known approaches to the synthesis of spinochrome C typically require several steps and give low yields [3]. We found that bromination of the relatively available dimethyl ether of echinochrome (2) [4] by Br2 in CCl4 containing H2O formed the dimethyl ether of spinochrome C (3) (30% yield) (Scheme 1). Compound 3 was probably a hydrolysis product that formed during the reaction of gem-dibromide 4. Heating diether 3 with conc. HBr (90°C) gave spinochrome C (1a, 40%) and its deacylation product spinochrome D (2,6,7-trihydroxynaphthazarine, 1b, 40%). A similar conversion (1a 1b) was reported before [5].

Synthesis of 6,8,9-Trihydroxy-2-Methyl-2H-Naphtho [2,3-b]Pyran-5,10-Dione, a Pigment of Echinothrix diadema, and Its Analogs

6,8,9-Trihydroxy-2-methyl-2H-naphtho[2,3-b]pyran-5,10-dione, a pigment of Echinothrix diadema, was synthesized. It existed as a mixture of two tautomers in CHCl3 solution according to IR spectroscopy. Its analogs 6,9-dihydroxy-2-methyl-2H-naphtho[2,3-b]pyran-5,10-dione and 6,9-dihydroxy-2-methyl-7,8-dichloro-2H-naphtho[2,3-b]pyran-5,10-dione were synthesized.

Synthesis of tricrozarin b, a pigment of Tritonia crocosmaeflora

Tricrozarin B (1) was isolated from bulbs of Tritonia crocosmaeflora Lemoine (Iridaceae) [1]. It, lomazarin (2) [2, 3], and tricrozarin A [4] are rare examples of polymethoxynaphthazarins isolated from higher plants. Tricrozarin B exhibited cytotoxic activity in vitro against Hela-S3 cells and antitumor activity in vivo against murine sarcoma S-180 [1] and melanoma B-16 [5]. The preparative production of tricrozarin B is interesting for further research of its biological activity and for use as starting material in the synthesis of other natural products and their analogs because of its poor availability. Long before it was observed in nature, trimethoxynaphthazarin 1 was known as a derivative of spinochrome D, a pigment of the sea urchins Pseudocentrotus depressus and Echinotrix calamaris [3, 6], that was prepared by its methylation using diazomethane [6, 7]. Tricrozarin B (1) was obtained earlier in three steps in overall yield ~10% using cycloacylation of dihydroxydimethoxybenzene 3 by chloromaleic anhydride (4) in an AlCl3:NaCl melt, methylation of the resulting dihydroxynaphthazarin 5 by diazomethane to protect the -hydroxy groups, and substitution of the Cl atom by methoxy in the resulting dimethoxynaphthazarin 6 using saturated MeONa in MeOH and refluxing for 48 h (Scheme 1) [8]. The conversion 6 1 required an enormous excess of reagent. Considering the overall low yield, this made this approach unsuitable for preparative production of 1.

Conversion of 2,3-dihydroxynaphthazarins to isoquinoline-1,3,4(2H)-trione derivatives

Abstract6(7)-(Di)alkyl- and 6(7)-(di)alkoxy derivatives of 2,3-dihydroxynaphthazarin were converted to 5,8-dihydroxyisoquinoline-1,3,4(2H)-trione derivatives under amination reaction conditions.

Chlorination of 2,3,6-trialkyl-5,8-dihydroxy-1,4-naphthoquinones with HCl-MnO2 in acetic acid. effective transformation of 2,3,6-trialkyl-2,3,7-trichloro-1,2,3,4-tetrahydronaphthalene-1,4-diones into 7-chloro-2,3,6-trialkyl-5,8-dihydroxy-1,4-naphthoquinones

Chlorination of 2,3,6-trialkyl-5,8-dihydroxy-1,4-naphthoquinones with HCl-MnO2 in acetic acid gave a mixture of 7-chloro-2,3,6-trialkyl-5,8-dihydroxy-1,4-naphthoquinones and 2,3,7-trichloro-2,3,6-trialkyl-1,2,3,4-tetrahydronaphthalene-1,4-diones, the latter being formed via addition of the second chlorine molecule to monochloro derivatives. The reduction of 2,3,7-trichloro-2,3,6-trialkyl-1,2,3,4-tetrahydronaphthalene-1,4-diones with sodium dithionite in alkaline medium resulted in the formation of 7-chloro-2,3,6-trialkyl-5,8-dihydroxy-1,4-naphthoquinones in high yield.