A short-step synthesis of naphtho[2,3-b]furan-4,9-dione

Phthalic anhydride in THF was added to 3-lithiofuran 2 in THF to give 3,3-di-(3-furyl)-1,3-dihy-droisobenzofuran-1-one 4 . On the other hand, 2 in THF was added to phthalic anhydride in THF to give 2-(3-furanoyl)benzoic acid 3 by the inverse addition method. Further, the parent naphtho[2,3-b]furan-4,9-dione 1 was obtained from the reaction of 3 with two equimolar amounts of LDA.     

Synthesis of derivatives of naphtho[2,3-b]furan-4,9-dione

The reaction of 2,3-dichloro-1,4-naphthoquinone with ketoenols has been studied. A series of substituted naphtho[2,3-b]furan-4,9-quinones has been synthesized and some of their reactions have been studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, Vol. 6, No. 7, pp. 867–870, July, 1970.     

A facile synthesis of 2-acetylnaphtho[2,3-b]furan-4,9-dione

Reaction of the parent naphtho[2,3-b]furan-4,9-dione 2 with various electrophilic reagents was difficult, and only nitration of 2 gave small amounts of 2-nitronaphtho[2,3-b]furan-4,9-dione 4 . Then 2-acetylnaphtho[2,3-b]furan-4,9-dione 1 was not obtained by the acetylation of 2 . On the other hand, compound 1 that is isolated from Tabebuia Cassinoides and has cytotoxic activity, was obtained from 3-lithiofuran in five steps.     

Nucleophilic substitutions of 2-chloronaphtho[2,3-b]furan-4,9-dione with amines

2-Chloronaphtho[2,3-b]furan-4,9-dione 4 was allowed to react with pyrrolidine to produce 2-(1-pyrrolidinyl)naphtho[2,3-b]furan-4,9-dione 8 in 64% yield. In a similar manner, the reaction of 4 with cyclic amines (piperidine, morpholine, 4-substituted piperazines, etc.) gave the desired compounds. 2-Dimethylaminonaphtho[2,3-b]furan-4,9-dione 20 and 2-propylaminonaphtho[2,3-b]furan-4,9-dione 23 were obtained from the reactions of 4 with amines in 67% and 48% yields, respectively. Furthermore, the reactions of 4 with acyclic amines (diethylamine, dipropylamine, isopropylamine, butylamine, etc.) gave the desired compound. Compound 4 was treated with sodium azide to give 2-azidonaphtho[2,3-b]furan-4,9-dione 28 in 42% yield. All these nucleophilic substitutions were carried out at room temperature. It was found that 4 showed high reactivity for amines. Unexpectedly, 2-morpholinonaphtho[2,3-b]furan-4,9-dione 13 was obtained from the reaction of 4 with 1-morpholino-1-cyclohexene.     

A new synthesis of naphtho[2,3-C]pyrroles. Conversion of naphtho[2,3-C]thiophene-4,9-diones to naphtho[2,3-C]pyrrole-4,9-diones

A series of 2-substituted-4,9-dihydronaphtho[2,3-c]pyrrole-4,9-diones was prepared by the reaction of 4,9-dihydronaphtho[2,3-c]thiophene-4,9-diones with primary amines under mild conditions. The presence of halogen in the naphtho[2,3-c]thiophene-4,9-dione and the presence of hydroxyl, ether, or tertiary amine functions in the amine reagent do not interfere with the course of the reaction.     

Synthesis of Naphtho[2,3-b]furan-4,9-diones Having a Trifluoromethyl Group under Conditions of Phase-Transfer Catalysis

Russian Journal of Organic Chemistry -     

Naphthindoles. 2. Naphtho[2,3-e]indole-4,9-diones and naphtho[2,3-f]indole-5,10-diones

The reactivity of naphtho[2,3-e]indole-4,9-dione and naphtho[2,3-f]indole-5,10-dione towards electrophiles (acylation, azocoupling, and the Mannich and Vilsmeier reactions) has been examined.For communication 1, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 783–786, June, 1989.     

Electronic and cytotoxic properties of 2-amino-naphtho[2,3-b]furan-4,9-diones

The electronic properties of a new set of cytotoxic 2-amino-naphtho[2,3-b]furan-4,9-dione derivatives (1-8) are evaluated. The electron delocalization of these compounds is described by means of their redox potentials and solvatochromic properties. The large solvatochromism of their intramolecular electron transfer band is analyzed using the linear solvation energy relationship method. In addition, this method determined the importance of the molecular environment, quantifying the interactions that compounds (1-8) establish with their surrounding media, with the capacity of acting as hydrogen-bond acceptors (HBA) and hydrogen-bond donors (HBD) and the dipolarity/polarizability being the most significant ones. As a result, a relationship between the electronic and the cytotoxic properties of these compounds is proposed.     

Structure Determination of New Isomeric Naphtho[2,3-b]furan-4,9-diones from Tabebuia avellanedae by the selective-INEPT technique

Beside the known naphthoquinones, dehydro-α-lapachone ( 17 ) and lapachol ( 20 ), four new naphtho[2,3-b]-furan-4,9-diones, i.e. the 2-acetyl-5-hydroxy. 2-acetyl-8-hydroxy. (?)-5-hydroxy-2-(1′-hydroxyethyl), and (±)-8-hydroxy-2-(1′-hydroxyethyl) derivatives 16, 15, 12 , and 13 , respectively, and the new compound benzo[b]furan-6-carboxaldehyde ( 8 ) have been isolated from a CHCl₃ extract of the inner stem bark of Tabebuia avellanedae LORENTZ ex GRISEB ., together with four known naphthofurandiones, a dihydroisocoumarin derivative, (?)–6-hydroxymellein, and five benzoic-acid and three benzaldehyde derivatives which have not been reported previously from this plant. Structure determination of the isomeric 5- and 8-hydroxynaphtho[2,3?b]furan-4,9-diones was carried out unambiguously by a combination of selective-INEPT experiments and X-ray crystallographic analysis.     

The preparation of 5-substituted thieno[2,3-b]furan-2-sulfonamides

An efficient synthetic route is reported for the preparation of thieno[2,3-e]furan-2-sulfonamides bearing oxygenated functionality at C-5. The method employs conversion of furan-3-carboxaldehyde to an intermediate that, in the key step, undergoes facile cyclodehydration to the fused [5,5] heterocycle under mild Knoevenagel conditions.     

Synthesis of bhimamycin B based on oxidative rearrangement of 4-acetylnaphtho[1,2-b]furan-5-ol to naphtho[2,3-c]furan-4,9-dione

The first total synthesis of bhimamycin B, a novel member of naphtho[2,3-c]furan quinone antibiotics, was achieved by oxidative skeletal rearrangement of 4-acetylnaphtho[1,2-b]furan-5-ol.     

Synthesis of 2-substituted naphtho[2,3-f]isoquinoline-7, 12-dione N-oxides

1-Acetylenyl-2-formylanthraquinone oximes cyclize upon heating in an ethanol-water solution of K₂CO₃ to give 2-substituted naphtho[2,3-f]isoquinoline-7,12-dione N-oxides.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 6, pp. 1447–1450, June, 1991.     

Efficient synthesis of cytotoxic quinones: 2-Acetyl-4H,9H-naphtho[2,3-b]furan-4,9-dione (6) and (±)-2-(1-hydroxyethyl)-4H,9H-naphtho[2,3-b]furan-4,9-dione (7)

From the ethanol extract of the stem bark of Tabebuia cassinoides (Lam.) DC (Bignoniaceae), Kingston and Rao [1] isolated two new furonaphthoquinones 6 and 7 that showed activity in KB cell culture assay (ED₅₀ 1.0 and 2.0 μg/ml, respectively). These values may be significant since lapachol, which has an ED₅₀ value of 4.4 μg/ml in the same assay, showed sufficient in vivo activity to reach clinical trial at the National Cancer Institute of the United States. The syntheses of these compounds ( 6 and 7 ) were realized in 36% overall yield starting from furan and phthalic anhydride.     

DABCO-catalyzed three-component reaction for the synthesis of naphtho[2,3-b]thiophene-4,9-diones

An efficient synthesis of naphtho[2,3-b]thiophene-4,9-diones has been developed via DABCO-catalyzed three-component reaction of 1,4-naphthoquinone derivatives, α,β-unsaturated ketones and hydrated sodium sulfide. The reaction is initiated by sequential Michael additions of sodium sulfide to α,β-unsaturated ketone and of generated anion to 1,4-naphthoquinone derivative, followed by intramolecular oxidative cyclization and aromatization. Various functional groups in the α,β-unsaturated ketones survive under the reaction conditions and naphtho[2,3-b]thiophene-4,9-diones are generated in good yields.     

Synthesis and photochemical properties of phenoxy derivatives of anthra[2,3-b]furan-5,10-dione

Nucleophilic replacement of the hydroxy groups in ethyl 4,11-dihydroxy-2-methyl-5,10-dioxo-5,10-dihydroanthra[2,3-b]furan-3-carboxylate by chlorine upon treatment with phosphorus acid chlorides gave the corresponding 4(11)-chloro derivatives which were converted into photochromic ethyl 4(11)-phenoxy-2-methyl-5,10-dioxo-5,10-dihydroanthra[2,3-b]furan-3-carboxylates. Photoinduced decomposition of the latter leads to the formation of phenol and fluorescent hydroxyanthra[2,3-b]furandiones.     

2-substituted 2,3-dihydro-5H-thiazolo[2,3-b]quinazoline derivatives

The synthesis of a series of 2-substituted 2,3-dihydro-5H-thiazolo[2,3-b]quinazoline derivatives is described. Some of the title compounds exerted antiinflammatory and immunomodulating activities in laboratory animal models.