Three different dimerizations of 2-bromo-3-methyl-1,4-naphthoquinones

Three types of dimeric naphthoquinones, which possess structurally diverse skeletons, can be prepared in one step from 2-bromo-3-methyl-1,4-naphthoquinones. 2,2'-Dimeric naphthoquinones were prepared by a one-pot Stille-type reaction via vinylstannanes. Oxepines are formed by unexpected domino reactions via 1,4-dihydroxynaphthalene species. Epoxides are formed by a Michael/Darzens reaction via the o-quinone methides.     

Reaction of Some Indoles with 1,4‐Naphthoquinones in the Presence of Pd(OAc)2

The reaction available for the introduction of an indole unit into the 1,4‐naphthoquinone skeleton is described. The reaction of the indoles with 1,4‐naphthoquinones in CH₃CN in the presence of Pd(OAc)₂ gave the corresponding 2‐(3‐indolyl)‐1,4‐naphthoquinones in moderate yield.     

The Synthesis of Some Fused Pyrazolo‐1,4‐Naphthoquinones

New fused pyrazolo‐1,4‐naphthoquinones were prepared from the reaction of hydrazines with 6‐(4‐methyl‐3‐pentenyl)‐1,4‐naphthoquinone. The reaction was extended to hydroxylamine to afford the corresponding isoxazolo‐1,4‐napthoquinone compound.     

An Efficient Synthesis of 5,6‐Dimethoxy 1‐ and 2‐Naphthols via Teuber Reaction

Based on the oxidation of 1,5‐naphthalenediol ( 4 ) and 6‐bromo‐2‐naphthol ( 9 ) via Teuber reaction, an efficient synthesis of 5,6‐dimethoxy‐1‐naphthol ( 1 ) and 5,6‐dimethoxy‐2‐naphthol ( 2 ) was achieved with high overall yield (16% for 1 and 25% for 2 ). The key steps of the synthetic strategy involved the oxidation of naphthols ( 4 and 9 ) to the corresponding naphthoquinones ( 5 and 10 ) and the conversion of 5,6‐dimethoxy‐2‐naphthaldehyde to 5,6‐dimethoxy‐2‐naphthol formate through Baeyer‐Villiger oxidation‐rearrangement.     

Direct synthesis of 5-substituted naphthoquinones

Peri-metalation of 4-(dimethylamino)-1-tert-butyldimethylsilyloxynaphthalene (5) followed by reaction with an electrophile and Jones' oxidation affords 5-substituted naphthoquinones.     

Reaction of dihydrolipoic acid with juglone and related naphthoquinones: unmasking of a spirocyclic 1,3-dithiane intermediate en route to naphtho[1,4]dithiepines

The reaction of dihydrolipoic acid (DHLA) with 5-hydroxy-1,4-naphthoquinone (juglone) gives rise to the novel naphtho[1,4]dithiepine derivatives through ring expansion of an unstable spirocyclic 1,3-dithiane intermediate, which was isolated and completely characterized. Reported herein is also the characterization of novel reaction products of DHLA with other naphthoquinones and the extension of the study to the spirocyclic adduct formed by reaction with a representative 2-substituted naphthoquinone.     

Regiocontrolled [3+2] quinone-nitrile oxide entry to type II polyketide building blocks

Bromine substituents on naphthoquinones effectively activate and orient the [3+2] dipolar cycloaddition reaction with nitrile oxides to generate regiodefined type II polyketide building blocks.     

Total synthesis of crisamicin A

Stereoselective total synthesis of natural product crisamicin A (1) was accomplished for the first time via the Pd/TMTU-catalyzed alkoxycarbonylative annulation to generate a unique cis-pyran-fused lactone, an intermolecular Diels-Alder reaction to construct the pyranonaphthoquinone unit, and a novel Pd-thiourea pincer complex-catalyzed homocoupling of functionalized naphthoquinones.     

An efficient synthesis of substituted anthraquinones and naphthoquinones

An efficient synthesis of 6,7-disubstituted naphthoquinones and 2,3,6,7-tetrasubstituted anthraquinones were developed using the reaction of thiophene dioxides and benzoquinone and naphthoquinone derivatives, respectively.     

Diels-Alder reactions between dienamides and quinones: stereochemistry of the cycloadditions and cytotoxic activity of the adducts

Tetrahydronaphthoquinones and tetrahydroanthraquinones bearing an amido group have been prepared by Diels-Alder reactions between (E)-1-(N-carbobenzyloxyamino)-1,3-butadiene (2) or (E)-1-(N-benzoyl-N-benzylamino)-1,3-butadiene (5) and benzoquinone or 5-substituted naphthoquinones. The stereochemistry of the cycloadditions was investigated. A high regioselectivity was observed in the reaction of the diene carbamate 2 with 5-methoxy and 5-acetoxy naphthoquinones. This latter gave the unexpected 1,8-regioisomer 3d. The cycloadditions of the dienamide 5 with naphthoquinones 1 (R = OH, OMe, OAc) are regiospecific. Assignment of the structure of the tetrahydroanthraquinone 6b is in good agreement with the known directing effect of the 5-hydroxy group of juglone 1b in analogous Diels-Alder reactions. With 5-methoxy and 5-acetoxy naphthoquinones, the opposite regiochemistry observed is consistent with the electron-donating influence of the methoxy or acetoxy group, making the C-3 carbon atom more electron deficient. Aromatization of the adducts 6b and 7c was accompanied by an unusual elimination of the amido moiety. Thus, 1-hydroxy and 1-methoxy anthraquinones were obtained. Reactions of the dienes 2 and 5 with benzoquinone gave the tetrahydronaphthoquinones 9 and 10 with an endo stereospecificity. Oxidation of 9 by activated manganese dioxide gave the naphthoquinone 11. These compounds were submitted to in vitro cytotoxic assays towards murine L 1210 leukemia cells and clonogenic human tumor cell line MDA-MB 231. The naphthoquinone derivatives 9, 10 and 11 had significant activities with IC50 less than or equal to 0.4 microgram/ml towards these two tumor cell systems.     

Glutathione reductase-catalyzed cascade of redox reactions to bioactivate potent antimalarial 1,4-naphthoquinones--a new strategy to combat malarial parasites

Our work on targeting redox equilibria of malarial parasites propagating in red blood cells has led to the selection of six 1,4-naphthoquinones, which are active at nanomolar concentrations against the human pathogen Plasmodium falciparum in culture and against Plasmodium berghei in infected mice. With respect to safety, the compounds do not trigger hemolysis or other signs of toxicity in mice. Concerning the antimalarial mode of action, we propose that the lead benzyl naphthoquinones are initially oxidized at the benzylic chain to benzoyl naphthoquinones in a heme-catalyzed reaction within the digestive acidic vesicles of the parasite. The major putative benzoyl metabolites were then found to function as redox cyclers: (i) in their oxidized form, the benzoyl metabolites are reduced by NADPH in glutathione reductase-catalyzed reactions within the cytosols of infected red blood cells; (ii) in their reduced forms, these benzoyl metabolites can convert methemoglobin, the major nutrient of the parasite, to indigestible hemoglobin. Studies on a fluorinated suicide-substrate indicate as well that the glutathione reductase-catalyzed bioactivation of naphthoquinones is essential for the observed antimalarial activity. In conclusion, the antimalarial naphthoquinones are suggested to perturb the major redox equilibria of the targeted infected red blood cells, which might be removed by macrophages. This results in development arrest and death of the malaria parasite at the trophozoite stage.     

Synthesis of 2‐(3‐indolyl)‐1,4‐naphthoquinones using 3‐iodoindoles

The usefulness of 3‐iodoindoles available for introduction of an indole unit is presented. The reaction of various halo‐3‐iodoindoles with 1,4‐naphthoquinone gave the corresponding 2‐(3‐indolyl)‐1‐4,naphthoquinones in moderate yields. The 3‐iodoindole was used for synthesis of a compound containing both naph‐thazarin and indole skeletons.     

Catalytic intramolecular crossed aldehyde--ketone benzoin reactions: a novel synthesis of functionalized preanthraquinones

Stereochemically and functionally rich polycyclic compounds are obtained by the first crossed aldehyde-ketone benzoin reaction in excellent yield under mild reaction conditions (5-20 mol % thiazolium salt, 10-70 mol % DBU, tBuOH, 40 degrees C, 30 min). This novel catalytic methodology offers a convenient approach to sophisticated molecular architectures useful for the stereocontrolled construction of polycyclic compounds as well as the fully regiocontrolled synthesis of anthra- and naphthoquinones.     

Enantioselective organocatalytic Michael-hemiketalization catalyzed by a trans-bifunctional indane thiourea catalyst

An efficient, convenient and enantioselective Michael-hemiketalization reaction has been developed for the synthesis of naphthoquinones. In this work, a novel trans-bifunctional indane thiourea catalyst has been reported to promote this process to afford high yields (up to 99%) and high to excellent enantiomeric excesses (90-98% ee).     

Reaction of Alkynes with Tetracarbonyl[Methoxy(2,4-Dimethoxyphenyl)Carbene]chromium: A Formal Synthesis of 7-Methoxyeleutherin

The reaction of alkynes with tetracarbonyl[methoxy(2,4-dimethoxyphenyl)carbene]-chromium, followed by oxidation, gives naphthoquinones as well as other cyclized products. This has been utilized in the preparation of (3) an intermediate in the synthesis of 7-methoxyeleutherin.     

Reactions of ketene acetals—IX: The synthesis of naphthoquinones from benzoquinones

Halogenobenzoquinones react with ketene acetals and give benzofurans, but in the presence of acetic acid, naphthoquinones are produced in variable yields. Some aspects of the reaction have been studied and the method has been applied to the synthesis of useful intermediates and of derivatives of some naturally occurring naphthoquinones such as tri-O-methylflaviolin 20 and tetra-O-methylspinochrome B23. Benzoquinones also react with conjugated ketene acetals without acid catalysis, providing convenient syntheses of ramentaceone 43, O-methylstypandrone 45 and 1,3,6,8-tetramethoxyanthraquinone 34.     

Substituted naphthoquinones as novel amino acid sensitive reagents for the detection of latent fingermarks on paper surfaces

In this paper, we present our preliminary studies into naphthoquinones as novel reagents for the detection of latent fingermarks on paper. Latent fingermarks deposited on paper substrates were treated with solutions of selected naphthoquinones in ethyl acetate/HFE-7100, with subsequent heating. The selected compounds were 1,4-dihydroxy-2-naphthoic acid, 1,2-naphthoquinone-4-sulfonate, 2-methoxy-1,4-naphthoquinone and 2-methyl-1,4-naphthoquinone. All of the tested compounds yielded purple-brown visible fingermarks, which also exhibited photoluminescence when illuminated with a high intensity filtered light source at 555 nm and viewed through red goggles. Indirect heat using an oven at 150 °C for 1 h was found to be superior to direct heat with an iron, which while providing faster development lead to increased levels of background colouration. Luminescence spectrophotometry revealed differences in photoluminescence characteristics for fingermarks developed with the different naphthoquinones, with excitation over the range 530-590 nm. Luminescence spectrophotometry of developed lysine, glycine and serine spots on paper was used to confirm that the naphthoquinones were reacting with amino acids in the latent fingermark.     

Effects of Different Carbon and Nitrogen Sources on Naphthoquinone Production of Cordyceps unilateralis BCC 1869

The production of six naphthoquinone derivatives, erythrostominone, deoxyerythrostominone, 4-O-methyl erythrostominone, epierythrostominol, deoxyerythrostominol, and 3,5,8-trihydroxy-6-methoxy-2-(5-oxohexa- 1,3-dienyl)-1,4-naphthoquinone, was examined during the growth of Cordyceps unilateralis BCC 1869 on different carbon and nitrogen sources. Erythrostominone production by the fungus accounted for more than 50% of total naphthoquinones, but production of each of the other five derivatives accounted for less than 20% of total naphthoquinones. The highest volumetric production rate of erythrostominone and overall naphthoquinone production rate were obtained on mannose as a sole carbon source and ammonium sulfate as a sole nitrogen source (4922.4 +/- 118.8 mg/[L.d] and 5.03 g/[L.d], respectively). The highest growth rate was obtained on arabinose (0.043 h-1), whereas the maximum overall naphthoquinone concentration was obtained on lactose (2 g/L) at 237 h. These naphthoquinones were produced with no pH control and were first detected at a pH of about 3.0 to 4.0. These results suggest that carbon and nitrogen influenced directly the production of naphthoquinones.     

Dipolar cycloaddition of rhodium-generated carbonyl ylides with p-quinones

[reaction: see text] The dipolar cycloaddition of carbonyl ylides generated by the rhodium-catalyzed decomposition of delta- and epsilon-carbonyl-alpha-diazoketones with p-quinones leads to both C=O and C=C addition products. The product ratio is solvent- and catalyst-dependent and has been optimized to favor formation of either product. The C=C addition products of naphthoquinones are used in the assembly of structures hybridizing the illudin and anthraquinone anticancer agents.     

Selective oxidation of naphthalene derivatives with ruthenium catalysts using hydrogen peroxide as terminal oxidant

The selective oxidation of naphthalene and its derivatives to give naphthoquinones has been investigated in detail. The reaction can be carried out effectively in the presence of a catalytic amount of Ru complexes (0.2 mol%) and phase transfer catalysts (PTC) using H₂O₂ as the terminal oxidant and water as the solvent. The effect of different ruthenium complexes, phase transfer catalysts, and the concentration of hydrogen peroxide were studied. Compared to previous procedures for this type of reactions, acidic solvents and high concentration of hydrogen peroxide are not necessary, which makes the reaction more environmentally friendly.