Facile synthesis of quinone epoxides and 5,6-epoxy-4-hydroxy-2-cyclohexenones via the retro-diels-alder reaction

From commercially available quinoes, quinone epoxides and 5,6-epoxy-4-hydroxy-2-cyclohexenones were easily prepared through the retro-Diels-Alder reactions under rather mild conditions.     

Conformational effects in acid-mediated ring opening of epoxides: a prominent role of the oxirane Walsh orbital

A kinetic study has been made of the BF(3)-mediated ring opening of two rigid conformers (alpha and beta) of m- and p-dimethyl-substituted homobenzoquinone epoxides spiro-linked with a twist-boat dibenzocycloheptene ring as compared with the conformationally mobile epoxides bearing diphenyl groups. The rates of the regioselective ring opening were dependent on the topological alignment of the dibenzocycloheptene ring as well as the substitution pattern of the quinone dimethyl groups, indicating pi-aryl participated orbital interaction with the vacant Walsh orbital of the oxirane ring.     

Acid-catalyzed rearrangement of aryl-substituted homobenzoquinone epoxides

The BF3-catalyzed reactions of diphenyl-substituted and endo-monophenyl-substituted homobenzoquinone epoxides proceeded through a regioselective oxirane ring opening followed by participation of a pi-aryl transannular cyclization to give the tricyclic diketo alcohols. The conformationally semirigid ethano-bridged diphenyl-substituted homologues also provided similar diketo alcohols and the subsequent ring-expanded cycloheptenedione (via a subsequent 1,2-acyl migration associated with cyclopropane ring opening), depending on the methyl-substitution pattern of the quinone frame. However, the exo-monophenyl-substituted and the rigid biphenyl-2,2'-diyl-substituted homobenzoquinone epoxides essentially remained unchanged.     

-Halogenoketones—XIII Chromone epoxides; their synthesis and acid-catalysed rearrangement

The chromone epoxide ring system has been synthesised. Base-catalysed cyclization and dehydrobromination of -bromo-o-acyl (aroyl) oxyacetopheones or 2-bromo-1, 3-diones yielded 3-substituted chromone epoxides. Acid-catalysed rearrangement of a 2-methylchromone epoxide in an aprotic solvent gave a 2-methylenech-romanonol, while a 3-methoxymethylchromone epoxide fragmented to chromonol under these conditions; in alchols, chromone epoxides gave 2-alkoxychromanonols.     

Synthesis and properties of fluorine-containing heterocyclic compounds. V. Trifluoromethyl-1,8- and 1,10-phenanthrolines

The condensation of ethyl trifluoroacetoacetate with various heterocyclic amines yielded 2-(trifluoromethyl)phenanthrolin-4-ones. The structures of these compounds were established from a study of their infrared and ultraviolet spectra. Substituted phenanthrolines were prepared by nucleophilic attack on a chlorophenanthroline. The oxidation of 5-methoxy-2-trifluoromethyl-1,10-phenanthroline yielded an o-quinone which was treated with typical quinone reagents. A molecular orbital calculation was carried out in an attempt to explain the ease of reduction of the 1,10-phenanthroline system and the colors of the reduced compounds.     

α-Halogenoketones—XIV: Studies in the chemistry of 2''-hydroxyacrylophenones

The chromone epoxide ring system has been synthesised. Base-catalysed cyclization and dehydrobromination of α-bromo-o-acyl (aroyl) oxyacetopheones or 2-bromo-1, 3-diones yielded 3-substituted chromone epoxides. Acid-catalysed rearrangement of a 2-methylchromone epoxide in an aprotic solvent gave a 2-methylenech-romanonol, while a 3-methoxymethylchromone epoxide fragmented to chromonol under these conditions; in alchols, chromone epoxides gave 2-alkoxychromanonols.     

The Structures of Some Products from the Photodegradation of the Pluramycin Antibiotics Hedamycin and Kidamycin

The photolability of the antitumor antibiotic hedamycin ( 1 ) was investigated by irradiation in different solvents in the presence or in the absence of oxygen. The products formed were separated chromatographically and their structures determined by NMR spectroscopy. Photolysis of 1 in the presence of oxygen gave only one isolable product, photohedamycin A ( 3 ), where ring E of hedamycin had been transformed into an enol ether. The reaction in the absence of oxygen yielded the photohedamycins B, C, and D ( 5, 6 , and 7 , respectively). In these compounds, one of the epoxides of hedamycin had been opened reductively, and in photohedamycin D ( 7 ) the substituent at C(8) - originally ring E of hedamycin - was now acyclic. In addition to these compounds, the photolyses yielded a large number of unstable minor products, which could not be isolated.     

PRODUCTS AND RELATIVE REACTION RATES OF THE OXIDATION OF TOCOPHEROLS WITH SINGLET MOLECULAR OXYGEN

Abstract— The relative reactivity of singlet molecular oxygen, 0₂(¹Δ_g), α-,β-,Γ-and δ with -tocopherol (vitamin E) was investigated using microwave discharge generation as a uniquely clean source of singlet oxygen and using a hydrocarbon solvent to approximate the membrane environment. The relative efficiencies of the tocopherols for O₂(¹Δg) were found to decrease in the order: D-α-tocopherol > D-β-tocopheroI > D–Γ-tocopherol > D-δ-tocopherol. The reaction products in all cases were found to be mixtures of quinone and quinone epoxides apparently resulting from decomposition of the primary product, the hydroperoxydienone.     

Synthesis, structure, and properties of benzoquinone dimer and trimers bearing t-Bu substituents

Highly soluble and stable quinone dimer and trimers were successfully yielded by introduction of t-Bu substituents. In X-ray structure analysis, the dimer quinone moiety was distorted into the boat shape, which was clarified by MO calculations. X-ray and UV/vis studies indicated that the covalently linked quinone moieties bear a large torsional angle. Nevertheless, the reduction potentials rose significantly with the order of monomer < dimer < trimer, indicating that the negative charge was efficiently delocalized within the radical anions.     

Chemo- and stereoselectivity in titanium-mediated regioselective ring-opening reaction of epoxides at the more substituted carbon

Chemo- and stereoselectivity in the ring-opening reaction of epoxides with a reagent prepared from allylmagnesium halide and chlorotitanium triphenoxide is described. It has been proven that the allylating reagent can also be used for the reaction of epoxides bearing a tert-butyl ester, amide, or acetal moiety, and that the epoxide cleavage regioselectively takes place at the more substituted carbon in all cases. Interestingly, while the reaction of acyclic 2,2,3-trialkyl epoxides or 3,3-disubstituted 2,3-epoxy alcohol derivatives with the allyltitanium reagent yielded the allylated products as an almost 1:1 diastereomixture, the ring-opening reaction of 2-substituted 2,3-epoxy alcohol derivatives stereospecifically proceeded through the anti pathway. The latter reaction is extremely useful for asymmetric construction of quaternary carbon centers.     

Epoxide polymers: Synthesis,stereochemistry, structure,and mechanism

Epoxide polymerization studies have yielded technically important catalysts and polymers. The polymers were studied by cleaving them with Group IA organometallics to monomer, dimer, and trimer glycol fragments. The identification of these glycol fragments has established that the crystalline polymers from the cis- and trans-2,3-epoxybutanes are respectively racemic and meso-diisotactic and that the amorphous polymer from the cis-oxide is disyndiotactic. These studies also showed that the amorphous fraction from propylene oxide polymerization with coordination catalysts contains substantial head-to-head and tail-to-tail segments. This work has led to a much better understanding of the mechanism of epoxide polymerization. These facts were established: (1) epoxides polymerize with inversion of configuration of the ring-opening carbon atom; (2) monosubstituted epoxides polymerize largely by attack on the primary carbon with a coordination catalyst; and (3) two or more metal atoms must be involved in the coordination polymerization of epoxides.     

Epoxyannulation II: Cyclization of ω-ketosulfonium salts

Treatment of 1,5 or 1,6 ketosulfonium salts with potassium t-butoxide has yielded cyclic epoxides of high stereochemical purity in good yield.     

Synthesis, complete 1H and 13C NMR assignment and crystal structure of novel epoxide derivatives of cytochalasin B

Five novel epoxide derivatives of cytochalasin B were synthesized. Reaction of cytochalasin B with t-BHP and BuLi led to selective epoxidation of the C-21/22 double bond to give a single monoepoxide, while reaction with m-CPBA yielded two diepoxides. Reaction of the monoepoxide with m-CPBA yielded two triepoxides. The relative configurations of the epoxides were elucidated by analogy with the natural product by means of spectroscopic methods; full assignment of NMR signals was achieved, and the absolute configuration was confirmed by X-ray crystallography.     

Glycosylidene Carbenes Part 12. A new synthesis and some reactions of spirooxiranes

The diazirine 1 , upon thermolysis or photolysis in either acetone or cyclohexanone, at different concentrations, yield the spiro epoxides 2 and 3 , and 4 and 5 , respectively (Scheme 1). Yield of 2 and 3 depended both on the temperature and the concentration, and correlated inversely with the yield of the major by-product, the enol-derived glycoside 6 . Other by-product were the benzyloxglycal 7 and the lactone azines 8 . ZnCl₂-Promoted methanolysis of 2 under mild condition yielded mixture of the uloside 9 and 10 (1.2:1); similarly, 4 yielded 11 and 12 (1.8:1; Scheme 2). More strongly acidic conditions converted 11 into 12 , evidencing that ZnCl₂-promoted methanolysis proceeds under kinetic control, which is rationalized. The diazirine 13 , upon thermolysis of Photolysis in either acetone of cyclohexanone, yielded the α-D -configurated spiro epoxides 14 and 16 , and the α-D -configurated dihydrooxazoles 15 and 17 , respectively (Scheme 3), which are either formed by ring-opening of ß-D -epoxides, by competitive interception of the initially formed, hypothetical addition products of the intermediate carbene to the ketones. The glycosylidene carbenes, derived from 1 or 13 are not very reactive towards ketones, yields are good only when sterically unhindered ketones are used in large excess.     

The reaction of aldrin,photoaldrin and isodrin with phthaloyl peroxide

The reactions of aldrin and photoaldrin with phthaloyl peroxide in carbon tetrachloride provided the respective carbon tetrachloride adducts, epoxides and cyclic phthalates of the corresponding cis-diols.Under the same conditions isodrin yielded the half-cage ketone (14), the cyclic phthalate (17) and the novel half-cage adduct (15).     

Optimized thiol derivatizing reagent for the mass spectral analysis of disubstituted epoxy fatty acids

A novel procedure is described for the derivatization of fatty acid epoxides in the presence of their corresponding diols. The acidic character of 2,3,5,6-tetrafluorobenzenethiol promotes favorable mass fragmentation of linoleate and arachidonate derived epoxide derivatives and reduces alkene isomerization to a manageable side reaction, eliminated through the addition of a thiol scavenger. After silylation, regioisomeric mixtures of epoxy- and dihydroxylipids are simultaneously detected and discriminated using gas chromatography with electron impact mass spectral detection. Silylated hydroxysulfanyloctadecanoids yielded instrumental detection limits of 5 pg/microl, sufficient sensitivity for the quantification of endogenous epoxylipids.     

The Synthesis of Aminoalcohols from Epoxides and Ammonia

In connection with another problem we had need for some simple aminoalcohols which were not commercially available. While textbooks make the reaction of ammonia and amines with epoxides appear inviting for the preparation of aminoalcohols, an examination of the literature yielded surprisingly few clearly written examples of the reactions of ammonia with epoxides and many of the good examples had undesirable features. For instance, one of the aminoalcohols desired was threo-3-amino-2-butanol. Lucas et al^2. reported an improved synthesis of this compound in 76% yield by reacting the meso-epoxide with an excess of concentrated aqueous ammonia. The drawbacks to their synthesis were the long recommended reaction time (10 days) and the large volume of water to be removed by distillation (about 2 liters per mole of product obtained). While the yield is reasonably good, all other examples of the reaction that we have found report lower yields (18–70%). Malinovski³ has reviewed the general reaction and treats the side reaction products obtained. Our procedure does not totally avoid side reactions, but the time involved and the good yields make this method more attractive than former procedures for the derivatives that we have prepared.     

Natural and synthetic quinones and their reduction by the quinone reductase enzyme NQO1: from synthetic organic chemistry to compounds with anticancer potential

The quinone reductase enzyme NAD(P)H: quinone oxidoreductase 1 (NQO1) is a ubiquitous flavoenzyme that catalyzes the two-electron reduction of quinones. This Perspective briefly reviews the structure and mechanism, physiological role, and upregulation and induction of the enzyme, but focuses on the synthesis of new heterocyclic quinones and their metabolism by recombinant human NQO1. Thus a range of indolequinones, some of which are novel analogues of mitomycin C, benzimidazolequinones, benzothiazolequinones and quinolinequinones have been prepared and evaluated, leading to detailed knowledge of the structural requirements for efficient metabolism by the enzyme. Potent mechanism-based inhibitors (suicide substrates) of NQO1 have also been developed. These indolequinones irreversibly alkylate the protein, preventing its function both in standard enzyme assays and also in cells. Some of these quinones are also potent inhibitors of growth of human pancreatic cancer cells, suggesting a potential role for such compounds as therapeutic agents.     

Azacycloalkanes from epoxides and aziridines

Methods of preparation of azetidines, pyrrolidines, and piperidines from epoxides and aziridines were analyzed. The possibility of epoxides conversion into aziridines was considered. The examples of application of azacycloalkanes in the medical and organic chemistry as biologically active substances and synthons for their preparation were calculated.     

Chemistry of fullerene epoxides: synthesis, structure, and nucleophilic substitution-addition reactivity

Fullerene epoxides, C??O(n), having epoxide groups directly attached to the fullerene cage, constitute an interesting class of fullerene derivatives. In particular, the chemical transformations of fullerene epoxides are expected to play an important role in the development of functionalized fullerenes. This is because such transformations can readily afford a variety of mono- or polyfunctionalized fullerene derivatives while conserving the epoxy ring arrangement on the fullerene surface, as seen in representative regioisomeric fullerene polyepoxides. The first part of this review addresses the synthesis and structural characterization of fullerene epoxides. The formation of fullerene epoxides through different oxidation reactions is then explored. Adequate characterization of the isolated fullerene epoxides was achieved by concerted use of NMR and LC-MS techniques. The second part of this review addresses the substitution of fullerene epoxides in the presence of a Lewis acid catalyst. Most major substitution products have been isolated as pure compounds and their structures established through spectroscopic methods. The correlation between the structure of the substitution product and the oxygenation pattern of the starting materials allows elucidation of the mechanistic features of this transformation. This approach promises to lead to rigorous regioselective production of various fullerene derivatives for a wide range of applications.