Studies on quinones. Part 23. Synthesis of azepinones fused to quinone systems

The Diels-Alder reactions of 3,4-dihydro-5H-1-benzazepine-2,6,9-trione 1 with butadiene, cyclopentadiene, 1-(E)-trimethylsiloxybutadiene 4 , and methacrolein dimethylhydrazone are described. Cycloaddition with the unsymmetrical dienes 4 and 18 occurs regiospecifically affording 5 and 19 respectively. The structure of 5 was established through naphthazepine 13 by comparison of its ¹H nmr with model compounds. The probable course of cycloaddition with 1-azadiene 18 is analyzed considering the polarization of azadiene 18 and the behavior of quinone 1 in the reaction with 4 . Michael addition of quinone 1 with isobutenylmorpholine 23 which afforded exclusively the cyclic O,N-acetal 24 or 25 and its convertion to benzepinquinone 26 or 27 is also reported.     

Bio-inspired quinone catalysis

Inspired by quinone-redox enzymes, small molecular quinone catalysts have been developed to promote C-H functionalization of amines. Recent efforts in this area have been summarized.     

Design of a cyclopropyl quinone methide reductive alkylating agent. 2

A cyclopropyl quinone methide is formed by elimination of a leaving group from an appropriately functionalized hydroquinone. The presence of a carbon spacer results in the formation of a fused ring rather than the classic methide species. Discussed herein is cyclopropyl quinone methide formation from a pyrido[1,2-a]indole ring system. Both nucleophilic and electrophilic attack on the fused cyclopropane ring results in pyrido[1,2-a]indole and azepino[1,2-a]indole products. The stereoelectronic effect plays less a role in the relatively flexible pyrido[1,2-a]indole system compared to its role in the pyrrolo[1,2-a]-indole system. A 13C label on the fused cyclopropane ring permitted the rapid identification of complex rearrangement products observed in this study.     

Electrochemical and spectroscopic characterization of quinone functionalized exfoliated graphite.

Natural graphite was exfoliated by thermal decomposition of graphite-bisulfate intercalation compound. Oxidative/reductive pre-treatment of exfoliated graphite was subsequently carried out to introduce various functional groups on the graphite surface. The resulting material was covalently modified with redox active quinones. The covalent modification was effected through oxygen containing functional groups formed on the graphite surface. The modified exfoliated graphite was characterized by infra-red (FTIR) and X-ray photoelectron spectroscopy (XPS). Electrochemical characterization of the pressed pellets of the modified graphite showed that the modification occurred at the edge sites. These electrodes were found to be very stable and the surface renewal was simply accomplished by polishing the surface using SiC emery sheets. Application of the benzoquinone modified electrode for the electrocatalysis of ascorbic acid oxidation was demonstrated.     

Unified synthesis of quinone sesquiterpenes based on a radical decarboxylation and quinone addition reaction

A unified synthesis of several quinone sesquiterpenes is described herein. Essential to this strategy is a novel radical addition reaction that permits the attachment of a fully substituted bicyclic core 16 to a variably substituted quinone 10. The addition product 15 can be further functionalized, giving access to natural products with a high degree of oxygenation at the quinone unit. The quinone addition reaction is characterized by excellent chemoselectivity, taking place only at conjugated and unsubstituted double bonds, and regioselectivity, being strongly influenced by the resonance effect of heteroatoms located on the quinone ring. These features were successfully applied to the synthesis of avarol (1), avarone (2), methoxyavarones (4, 5), ilimaquinone (6), and smenospongidine (7), thereby demonstating the synthetic value of this new method.     

A new route to the synthesis of ellipticine quinone from isatin

1-(2-Oxo-2-(pyridin-4-yl)ethyl)indoline-2,3-dione can be prepared and converted by treatment with sodium hydroxide into 2-isonicotinoyl-1H-indole-3-carboxylic acid as a key intermediate which can be transformed into ellipticine quinone in a two step sequence.     

Electrocoagulation of quinone pigments

Some representative quinones, viz. one naphthoquinone (plumbagin) and five anthraquinones (alizarin, purpurin, chrysazin, emodin, and anthrarufin), were subjected to electrocoagulation. It was found that the rate and extent of coagulation of these compounds appears to correlate with the number and relative position of their phenolic substituent groups, and that all of the coagulated quinones could be recovered. Attempts were then made to electrochemically isolate three quinones, namely plumbagin, morindone and erythrolaccin, from natural sources.     

Sterically congested adamantylnaphthalene quinone methides

Five new (2-adamantyl)naphthol derivatives (5-9, quinone methide precursors, QMP) were synthesized and their photochemical reactivity was investigated by preparative photolyses, fluorescence spectroscopy, and laser flash photolysis (LFP). Excitation of QMP 5 to S(1) leads to efficient excited state intramolecular proton transfer (ESIPT) coupled with dehydration, giving quinone methide QM5 which was characterized by LFP (in CH(3)CN-H(2)O, λ(max) = 370 nm, τ = 0.19 ms). On irradiation of QMP 5 in CH(3)OH-H(2)O (4:1), the quantum yield of methanolysis is Φ = 0.70. Excitation of naphthols QMP 6-8 to S(1) in CH(3)CN leads to photoionization and formation of naphthoxyl radicals. In a protic solvent, QMP 6-8 undergo solvent-assisted PT giving QM6 or zwitterion QM8 that react with nucleophiles delivering adducts, but with a significantly lower quantum efficiency. QMP 9 in a protic solvent undergoes two competitive processes, photosolvolysis via QM9 and solvent-assisted PT to carbon atom of the naphthalene giving zwitterion. QM9 has been characterized by LFP (in CH(3)CN-H(2)O, λ(max) > 600 nm, τ = 0.9 ms). In addition to photogenerated QMs, two stable naphthalene QMs, QM10 and QM11 were synthesized thermally and characterized by X-ray crystallography. QM10 and QM11 do not react with H(2)O but undergo acid-catalyzed fragmentation or rearrangement. Antiproliferative activity of 5-9 was investigated on three human cancer cell lines. Exposure of MCF-7 cells treated with 5 to 300 nm irradiation leads to an enhanced antiproliferative effect, in accordance with the activity being due to the formation of QM5.     

氢醌卟啉的合成及其对醌的分子识别

利用氢醌与2-硝基卟啉直接反应，合成了2-(2’，5’—二羟基苯基)—5，10，15，20-四苯基卟啉，并利用紫外光谱、荧光光谱、电化学方法考察了它们对酯的分子识别，结果显示2—(2’，5’—二羟基苯基)-5，10，15，20-四苯基卟啉对醌具有较好的识别能力。     

Oxyfunctionalization of calixarene quinone rings

The epoxidation of quinone rings of calixquinones represents a valid route for the introduction of oxygenated functionalities into the de-tert-butylated calixarene walls originating cis-diepoxy-p-dione moieties. Carbonyl reduction of these systems leads to hybrid calixarenes containing dianhydroinositol moieties (calixinositols) belonging to the calixcyclitols family. The regio- and stereochemistry of these derivatives was determined by 2D NMR studies, in conjunction with MM3 calculations and X-ray crystallography.     

Experiments on the total synthesis of Lysolipin I. Part II. Michael addition of 1,3-cyclohexanedione to quinone acetals

Base-catalyzed reaction of 1,3-cyclohexanedione ( 3 ) with the quinone monoacetals 4 and 7 leads to the polycyclic products 5 and 8 , respectively, and in the case of 4 to variable amounts of dibenzofuranone 6 . The 2-arylcyclohexanedione 9 , on the other hand, is isolated from the reaction of 3 and bisacetal 11 catalyzed by ZnCl₂ (Scheme 2). Treatment of the adduct 8 with (CH₃O)₂SO₂/K₂CO₃ results in cleavage of teh heterocyclic ring by a retro-Michael reaction affording teh liable enone 23 which was further transformed to 24 by selective hydrogenation. The 8-acetoxydibenzofuranone 22 is obtainable from 8 by acid treatment and acetylation (Scheme 4). The reactions of the silylenol ethers 27 and 35 with quinone monoacetals were very complex (Scheme 6). The desired arylcyclohexanone derivatives 28 and 36 were formed in very low yields. Under certain conditions (elevated temperature or strong Lewis acids as catalysts), single-electron transfer or addition to the ene-acetal rather than to the enone function of the quinone monoacetals became predominant. In connection with this study, the sensitive 2-methoxy-p-benzoquinone monoacetals 15 (Scheme 3) and 29 (Scheme 6) have been prepared and characterized.     

Photochemical rearrangements of quinone monoketals. Synthesis of substituted cyclopentenones

The irradiation of quinone ethylene monoketals in acetic acid leads in high yield to substituted 4-(alkoxycarbonyl) cyclopentenones.     

Amine–quinone polyimides

Two dianiline monomers were prepared by the reaction of either 4,4′‐methylenedianiline or 4,4′‐oxydianiline with 1,4‐benzoquinone. These monomers were used to synthesize a series of amine–quinone polyimides by condensation with either 3,3′,4,4′‐benzophenonetetracarboxylic dianhydride or 4,4′‐(hexafluoroisopropylidene) diphthalic anhydride to make the corresponding polyamic acid. The polyamic acids were converted to the polyimides by thermal imidization at 290 °C. The amine–quinone polyimides gave freestanding films with tensile strengths in the range of 90 to 150 MPa and Young's moduli of 0.9 to 1.5 GPa. The thermal decomposition temperature under nitrogen was 440 to 480 °C and the glass‐transition temperature was in the range of 280 to 310 °C. The amine–quinone polyimides had the excellent thermal and mechanical properties that one expects for polyimides. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 4044–4049, 2001     

Purification and properties of cellobiose: quinone oxidoreductase from Sporotrichum pulverulentum.

Cellobiose: quinone oxidoreductase was purified by ammonium sulfate precipitation, SP-Sephadex C-50 chromatography, and hydroxylapatite column chromatography. The purified enzyme is homogeneous by ultracentrifugal and SDS-gel electrophoretic analyses. The enzyme is a flavoprotein with FAD as the prosthetic group and produces cellobiono-delta-lactone as the product of cellobiose oxidation. Cellopentaose is also oxidized but no oxidation of cellulose could be detected. The enzyme oxidizes lactose and 4-beta-glucosylmannose but not 4-beta-mannosylglucose which implicates the C-2-hydroxyl of the non-reducing end of the disaccharide as important for substrate specificity.     

Studies in the quinone field

The condensation of p-benzoquinone with substituted N-benzyl-β-aminocrotonic esters has been studied. A series of derivatives of 1-benzyl-5-hydroxyindole containing various substituents in the benzene nucleus of the benzyl radical has been obtained.     

Synthesis of quinone derivatives of quinocarcin

O-Demethyl-DX-52-1 (3a) was prepared from quinocarcin (1) in two steps (cyanation and O-demethylation). Upon treatment with Fremy's salt, 3a and its esters 3b, 3c afforded the desired quinone 4-6 in good yields. Various substituted quinones 12-37, 47-50 were prepared from 4-6 by Thiele acetylation followed by hydrolysis of acetates and halogenation, by direct addition of amine, alcohol and mercaptan, and by epoxidation and subsequent opening of the epoxide ring with aniline. The quinonemonoketals 39b and 40 were obtained from the corresponding methoxyphenols 7b and 38b. Addition of hydroxylamine gave the quinoneoxime 44 regiospecifically. The antitumor activity of the bis-methylthioquinone (37) among the various derivatives was the most promising.     

Carbon-13 NMR of quinone methides

The ¹³C NMR spectra of four ortho- and seven para-quinone methides were assigned using chemical shift and long-range carbon-proton coupling information. The carbonyl shifts are compared with those in ortho- and para-benzoquinones. The chemical shifts of the carbonyls of the p-quinone methides are observed at δ 186.2–186.4 for the three ortho-di-tert-butyl-substituted compounds and at δ 180.7–181.5 for the four ortho-oxy-substituted compounds. In the three o-quinone methides with meta, para-dioxy substituents, the carbonyl signals are at δ 184.2–185.4. The carbonyl signal of the one o-quinone methide with no oxygen substitution is shifted downfield to δ 200.9, apparently as a result of hydrogen bonding to the nearby hydroxyl.