Synthesis and properties of water-soluble 5,8-dihydroxy-1,4-naphthoquinone thioglucosides structurally related to echinochrome

Abstract

Acetylated hydroxynaphthazarin di-and trithioglucosides structurally related to echinochrome were synthesized. Their deacetylation by the action of sodium methoxide in methanol and the effect of hydroxy groups on this process were studied. Water-soluble echinochrome thioglucosides were synthesized for the first time.Naphthoquinones are widespread in nature, and they exhibit diverse physiological activity [1, 2]. Among these compounds, polyhydroxynaphthoquinones of the naphthazarin (5,8-dihydroxy-1,4-naphthoquinone) series occupy a particular place. Due to specificity of their structure, they are capable of effectively trapping free radicals and binding Fe 2+ ions responsible for the formation of active oxygen species [3,4]; excess concentration of the latter in an organism promotes development of various pathological states [5].Echinochrome (I, 6-ethyl-2,3,5,7,8-pentahydroxy-1,4-naphthoquinone) is a pigment isolated from the sea urchin shell (Echinodea); it was used as active substance of the drug Gistokhrom for the treatment of eye injuries and burns, as well as of myocardial infarction [6]. The results of recent experiments in animals showed that Gistokhrom is also effective in the treatment of hemorrhagic stroke [7,8]. Unfortunately, echinochrome is poorly soluble in water. In order to improve the solubility and bioavailability, echinochrome was converted into the corresponding tris-Oglucoside [9]. However, the latter turned out to be unstable: it decomposed shortly after isolation.S-Glycosides are known to be more stable toward acids and bases than their O-glycoside analogs [10]. It was shown previously that chlorine atoms in the naphthazarin core are readily replaced by acetylglucoside residues under conditions of base catalysis [11]. It was also found that nucleophilic addition of chlorine atoms is accompanied by Michael 1,4-addition of thiols to the quinoid ring [12].The present article describes the synthesis of acetylated naphthazarin S-glucosides that are structurally related to echinochrome and deacetylation of the acetylglucosides by the action of sodium methoxide, which afforded stable water-soluble thioglucosides of the echinochrome series; the effect of hydroxy groups in the naphthazarin core on the deacetylation process was also studied.

Synthesis and Screening of Anti-HSV-1 Activity of Thioglucoside Derivatives of Natural Polyhydroxy-1,4-Naphthoquinones

“…Subsequent saponification of acetyl derivatives 11 to 13 under MeONa/MeOH treatment (method A) led to the targeted thioglucosides 15 to 17 in good yields of 75% to 82%. 25 Dichloroquinone 9 with 2 acidic β-hydroxyl groups in the quinone part did not react with thioglucose 10 under these conditions. Apparently, the ionization of 2 quinonoid hydroxyl groups significantly reduced the activity of chlorine atoms to substitution.…”

“…Starting dichloronaphthoquinones 6 to 9 were synthesized as published in papers. 25,32 Preparation of 14 Dichloronaphthoquinone 9 (100 mg, 0.343 mM) and acetylthioglucose 10 (300 mg, 0.82 mM) were dissolved in DMSO (4 mL), added finely powdered K 2 CO 3 95 mg (0.69 mM) and mixed for 1 hour until complete conversion of quinone 9 with R f 0.72(A) into a new red compound with R f 0.33(A). Reaction mixture was acidified by 2N hydrochloric acid, diluted with CHCl 3 (15 mL), organic layer washed with water (2 × 10 mL), dried with Na 2 SO 4 , evaporated, and the residue subjected to preparative TLC on SiO 2 , eluting with system A, yielding 14 as a dark red solid (276 mg, 85%).…”

Antileukemic Properties and Structure-Activity Relationships of O- and SGlycosylated Derivatives of Juglone and Related 1,4-Naphthoquinones

“…These compounds were synthesized and purified as described previously [9][10][11][12][13][14][15][16][17][18][19][20] and were pure in accordance with chromatographic and NMR data. RPMI medium was from Gibco Invitrogen Corporation (Carlsbad, CA, USA).…”

“…In 1983 -2010 years, we reported syntheses, structure elucidations, and biological activities of about 100 new O-or S-glycosides of 1,4-naphthoquinones and products of their intramolecular cyclisation [9][10][11][12][13][14][15][16][17][18][19][20]. Many of these compounds, in distinct from the earlier studied those, have a carbohydrate moiety attached to the quinone part of the molecule via sulfur atom (thioglycosyl group).…”

Synthesis and Evaluation of Antimicrobial and Cytotoxic Activity of Oxathiine-Fused Quinone-Thioglucoside Conjugates of Substituted 1,4-Naphthoquinones

“…Naphthoquinones often possess poor solubility which has hampered their practical use. The conjugation of naphthoquinones with non-toxic carbohydrates is one of the most successful ways for improving their solubility [ 15 , 16 , 17 , 18 , 19 ]. Moreover, the conjugation of naphthoquinones with carbohydrates led to novel structures with new types of biological activity [ 20 , 21 ].…”