Stereoisomeric Epoxides Research Articles

Reactions of N- and C-alkenylanilines: IX. Synthesis, oxidation, and nitration of some 7-methyl-1,3a,4,8b-tetrahydrocyclopenta[b]indoles

Heating of 4-acyl-3-iodo-7-methyl-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indoles in piperidine gave 4-acyl-7-methyl-1,3a,4,8b-tetrahydrocyclopenta[b]indoles which were oxidized with KMnO4 to obtain the corresponding 4-acyl-7-methyl-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole-1,2-diols. Oxidation of 4-acyl-7-methyl-1,3a,4,8b-tetrahydrocyclopenta[b]indoles at the olefinic double bond with hydrogen peroxide in acetonitrile in the presence of formic acid afforded stereoisomeric epoxides with cis and trans orientation of the nitrogen-containing and oxirane rings. Nitration with a mixture of ammonium nitrate and trifluoroacetic anhydride produced 5-nitro derivatives. The structure of 1-{(1aR*,1bR*,6bS*,7aS*)-5-methyl-1a,1b,2,6b,7,7ahexahydrooxireno[4,5]cyclopenta[1,2-b]indol-2-yl}ethanone was determined by X-ray analysis.

Stereoselective epoxidation of the last double bond of polyunsaturated fatty acids by human cytochromes P450

Cytochromes P450 (CYPs) metabolize polyunsaturated long-chain fatty acids (PUFA-LC) to several classes of oxygenated metabolites. Through use of human recombinant CYPs, we recently showed that CYP1A1, -2C19, -2D6, -2E1, and -3A4 are mainly hydroxylases, whereas CYP1A2, -2C8, -2C9, and -2J2 are mainly epoxygenases of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), respectively. It is worth noting that the last double bond of these PUFAs, i.e., omega6 in AA or omega3 in EPA and DHA, respectively, was preferentially epoxidized. In this study, we have characterized the stereoselectivity of this epoxidation reaction by comparison with the PUFA-LC epoxide stereoisomers obtained from the enantioselective bacterial CYP102A1 F87V. The stereoselectivity of the epoxidation of the last olefin of AA (omega6), EPA (omega3), or DHA (omega3) differed between the CYP isoforms but was similar for EPA and DHA. These data give additional insight into the PUFA-LC epoxide enantiomers generated by the hepatic CYPs.

Azabrendanes. III. Synthesis of stereoisomeric exo‐ and endo‐5‐acylaminomethyl‐exo‐2,3‐epoxybicyclo[2.2.1]heptanes and their reduction by lithium aluminum hydride

AbstractA number of stereoisomeric N‐[aryl(alkyl, cycloalkyl)carbonyl]‐exo(endo)‐5‐aminomethylbicyclo[2.2.1]hept‐2‐enes have been synthesized from bicyclo[2.2.1]hept‐2‐en‐exo(endo)‐5‐carbonitrile via reduction of the latter by lithium aluminum hydride and subsequent reactions of the resulting amines with aryl(alkyl, cycloalkyl)carbonyl chlorides and anhydrides. The direction of reaction of amides with peroxy acids does not depend on orientation of substituents in the bicyclic fragment: that is, for both exo‐ and endo‐isomers the epoxidations are completed by the formation of N‐[aryl(alkyl, cycloalkyl)carbonyl]‐exo(endo)‐5‐aminomethyl‐exo‐2,3‐epoxybicyclo[2.2.1] heptanes. The reduction of stereoisomeric epoxides by lithium aluminium hydride proceeds in different directions; that is, isomers with an exo‐oriented amido group form the substituted exo‐5‐alkylaminomethyl‐exo‐2,3‐epoxybicyclo[2.2.1]heptanes and the reactions of epoxides of endo‐amides are accompanied by intramolecular cyclization and completed by the formation of N‐[aryl(alkyl, cycloalkyl)]‐exo‐2‐hydroxy‐4‐azatricyclo[4.2.1.03,7]nonanes. The structures and stereochemical homogenity of the products have been confirmed by the analysis of 1H and 13C NMR spectra, correlation spectroscopy, and nuclear Overhauser enhancement spectroscopy experiments. We discuss the behavior of epoxides and provide an analysis of the coefficients of the atomic orbitals in the molecular orbital–linear combination of atomic orbitals equation (AM1 method). © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:119–130, 2001

A general assay for antibody catalysis using acridone as a fluorescent tag.

A simple and highly sensitive catalysis assay is demonstrated based on analyzing reactions with acridonetagged compounds by thin-layer chromatography. As little as 1 pmol of product is readily visualized by its blue fluorescence under UV illumination and identified by its retention factor (Rf). Each assay requires only 10 microliters of solution. The method is reliable, inexpensive, versatile, and immediately applicable in repetitive format for screening catalytic antibody libraries. Three examples are presented: (i) the epoxidation of acridone labeled (S)-citronellol. The pair of stereoisomeric epoxides formed is resolved on the plate, which provides a direct selection method for enantioselective epoxidation catalysts. (ii) Oxidation of acridone-labeled 1-hexanol to 1-hexanal. The activity of horse liver alcohol dehydrogenase is detected. (iii) Indirect product labeling of released aldehyde groups by hydrazone formation with an acridone-labeled hydrazide. Activity of catalytic antibodies for hydrolysis of enol ethers is detected.

Photosensitized oxidation of furans. Part 16. Selective formation and chemical properties of 3H-1,2-dioxoles: a new class of cyclic peroxides

Direct evidence is provided for the selective formation of the 3H-1,2-dioxoles 1 by thermal conversion of the furan endo-peroxides 2 substituted at C-1 with an alkoxy substituent and at C-5 with an electron-withdrawing group. The thermally unstable dioxoles 1 when heated give, by concerted rearrangements, in addition to the keto esters 3 and 4, the epoxides 5, or 5 and 6. Those like 1c–e, which are disubstituted at C-3, yield the two stereoisomeric epoxides 5c–e and 6c–e, while dioxoles 1a and 1b, which bear a hydrogen atom at C-3, give stereospecifically the epoxides 5a and b. The stereospecificity of the latter reaction is suggested to be due to the preferential conformation 10, which the peroxides 1a,b assume on formation from the related endo-peroxides. Some other chemical properties of the new class of peroxides are reported.

Synthesis, three-dimensional structure, and stereochemistry of epoxidation of 1-chloro-2-methylenecyclohexane

1. Epoxidation of 1-chloro-6-methylenecyclohexane occurs stereoselectively, leading to the formation of two stereoisomeric epoxides, with the trans-isomer predominating. 2. 1-Chloro-2-methylenecyclohexane and its isomeric epoxides exist predominantly in a conformation with an axial orientation of the C-Cl bond.

ChemInform Abstract: Acid‐Catalyzed Rearrangement of Butyl 2‐0‐ Acetyl‐4,5‐anhydro‐3,6‐dideoxyhexaldonate.

AbstractThe mixture of the stereoisomeric epoxides (I) and (II), prepared by acetylation of the corresponding alcohols, can be separated into the pure components by a chromatographic procedure, but the rearrangement with one of these was performed only on an analytical scale and was monitored by TLC.

Epoxidation of 4?-chloro-3(10)carene

1. The epoxidation of 4β-chloro-3(10)-carene proceeds without steric specificity to give two stereoisomeric epoxides with predominance of the trans isomer. 2. 4β-Chloro-3(10)-carene and its isomeric epoxides have half-chair conformation with equatorial C-Cl bonds.

Synthetic studies on terpenic compounds—XV : Synthesis of methyl 14β-hydroxy-7β:8β,9β:11β,12α:13α-triepoxyabietan-18-oate, complete B/C ring model of antileukemic triptolides, from levopimaric acid

Stereospecific construction of the hydroxytriepoxide system present in triptolide 1 and tripdiolide 2 has been explored starting from levopimaric acid 3. 8α:14α:14α,12α:13α-Diepoxide 9 derived from 3 was converted to the epoxy dienone 16 by four steps process. The 9,11-epoxide group was introduced stereospecifically by oxidation with m-chloroperbenzoic acid to produce diepoxide 20. Epoxidation of the 14β-hydroxy derivative 33 with m-chloroperbenzoic acid or by a photochemical method afforded the title compound 36 which possesses the complete B/C ring functionality of 1 and 2. The stereochemistry of the epoxy rings in 36 was confirmed by X-ray crystallographic analysis of the isomeric triepoxide 37. The result of antitumor tests of the stereoisomeric epoxides obtained in this study is described.

Linear‐reactor‐infrared‐matrix and microwave spectroscopy of the cis‐2‐butene gas‐phase ozonolysis

AbstractInvestigation of the formation of complex products in the gas‐phase ozonolysis of cis,‐2‐butene by linear‐reactor‐infrared‐matrix and linear‐reactor‐microwave spectroscopy is reported. The following species have been unequivocally detected: secondary 2‐butene ozonide, acetic acid, peracetic acid, glycolaldehyde, dimethyl ketene, the simple and mixed anhydrides of formic and acetic acid, 2,3‐epoxybutane and 2‐butanone, besides polyatomic products already known. In contrast, the primary ozonide has been detectable neither by LR.‐MW. nor by LR.‐IR. Observation of both stereoisomeric epoxides and kinetic modelling are used to support the intermediate formation of the O'Neal‐Blumstein radical CH3CH(O2)CH(O)CH3 and the existence of a reaction channel in which the two carbon atoms of the C, C double bond of the olefin remain connected. As the dominant reaction path a mechanism with a Criegee type split into methyldioxirane (ethylidene peroxide) and acetaldehyde is considered and subsequently proposed to explain formation of many complex products by either unimolecular or bimolecular processes of the peroxide. For the reactions considered, thermochemical estimates of reaction enthalpies and activation data are included. Kinetic modelling for a partial reaction mechanism involving at least two different paths of decay of the O'Neal‐Blumstein biradical into Criegee‐type intermediates and the 2, 3‐epoxybutanes is discussed.

Preparation of polymer-supported peroxy-acids and their use to oxidise olefins to epoxides

Treatment of carboxy-substituted polystyrene resins with hydrogen peroxide in methanesulphonic acid gave resins containing aromatic peroxy-acid residues (3.5–4.0 mmol g–1). The resins generally reacted with di- and tri-substituted olefins in tetrahydrofuran at 40 °C to give epoxides (or products derived from epoxides) in yields greater than 50%. Monosubstituted olefins reacted poorly. In cases where mixtures of stereoisomeric epoxides were formed the proportions of the isomers were essentially the same as those obtained by using monomeric aromatic peroxy-acid reagents.

Derivatives of 2-alkoxy-5,6-dihydro-2 h-pyran as starting materials in the synthesis of monosaccharides : Part IX. Total synthesis of methyl 3,4-dideoxy- and 3,4,6-trideoxy- D,L-hex-3-enopyranosides

The synthesis of the title compounds from the butyl ester of cis,trans-5,6-dihydro-2-methoxy-2 H-pyran-6-carboxylic acid, which was reduced to cis,trans-5,6-dihydro-6-hydroxymethyl-2-methoxy-2 H-pyran is described. Epoxidation of the latter compound yielded four stereoisomeric epoxides, which were separated by column chromatography. Each epoxide was, in turn, treated with dimethylamine to give the corresponding methyl 3,4-dideoxy-3-dimethylamino- D,L-hexopyranoside. Hydrogen-peroxide oxidation of the aminodeoxy sugar gave the N-oxide, which was subjected to a Cope degradation to afford methyl 3,4-dideoxy- D,L-hex-3-enopyranoside. The same reaction scheme was applied to trans-5,6-dihydro-2-methoxy-6-methyl-2 H-pyran, affording methyl 3,4,6-trideoxy-α- D,L- erythro- and threo-hex-3-enopyranosides; β anomers were obtained by acid-catalyzed anomerization. The n.m.r. data are given for unsaturated sugars and their O-acetyl derivatives.

Preparation of stereoisomeric functionally

The oxidation of trans-2,6-diethoxy-Δ 3-dihydropyran with perbenzoic acid gave a mixture of stereoisomeric epoxides, from which one individual isomer was isolated. The configuration and conformation of the epoxide obtained was established by PMR spectroscopy. 2,6-Diethoxy-3-hydroxy-4-dialkylaminotetrahydropyrans were obtained by the reaction of 2,6-diethoxy-3,4-epoxytetrahydropyran with dimethylamine and piperidine; the structural direction of the opening of the epoxide ring was studied by mass spectrometry.

Preparation and diastereoisomerism of four substituted epoxycyclopentanones

AbstractEpoxidation of 4‐acetoxy‐2‐(6′‐methoxycarbonylhexyl)‐2‐cyclopenten‐1‐one in alkaline medium yielded the two possible diastereoisomers of 2,3‐epoxy‐4‐hydroxy‐2‐(6′‐methoxycarbonylhexyl)‐1‐cyclopentanone. The structure and configuration of these compounds have been elucidated by first order analysis of the normal and spindecoupled proton magnetic resonance spectra. Both stereoisomeric epoxides can also be obtained via an alternative synthetic route by epoxidation of 2‐(6′‐carboxyhexyl)‐4‐hydroxy‐2‐cyclopenten‐1‐one. The separate cis and trans isomers of 2‐(6′‐carboxyhexyl)‐2,3‐epoxy‐4‐hydroxy‐1‐cyclopentanone are correlated with the stereoisomers of 2,3‐epoxy‐4‐hydroxy‐2‐(6′‐methoxycarbonylbexyl)‐1‐cyclopentanone by interconversion with diazomethane as well as by comparison of the proton spectra.

Analogs of corticosteroids

1. The behavior of stereoisomeric epoxides of 1-acetyl-4-t-butylcyclohexene-1 under conditions of acetolysis was studied. 2. The 2-acetate of lα-acetyl-4β-t-butylcyclohexane-1β,2α-diol is formed exclusively by axial attack of acetic acid at the C2-reaction center of 1α-acetyl-1β,2β-epoxy-4β-t-butylcyclohexane. 3. In the acetolysis of 1β-acetyl-1α,2α-epoxy-4β-t-butylcyclohexane is formed the 2-acetate of 1,β-acetyl-4β-t-butylcyclohexane-1α,2β-diol, probably by axial attack at the C2 in a “half-tub” conformation and the 1-acetate of 1α-acetyl-4β-t-butylcyclohexane-1β,2α-diol by axial attack at the Cl in the “halfchair” conformation. 4. The complex course of acetolysis of 1β-acetyl-1α,2α-epoxy-4β-t-butylcyclohexane at a higher temperature is caused by partial isomerization of the product of trans-diaxial opening — the tertiary monoacetate of the trans-diol. 5. The 1,2-diacetates of four isomeric 1-acetyl-4-t-butylcyclohexane-1,2-diols were synthesized, and their behavior under conditions of mild basic hydrolysis was examined. 6. The secondary acetoxy group of the diacetate saponifies more easily than the tertiary. During saponification of the diacetates of the ketodiols, a migration of the acyl from the tertiary position to the secondary by an orthoester mechanism is observed.

Über die Synthese einer Modellverbindung mit dem Chromophor der Toxiferine. 1. Mitteilung über Indole, Indolenine und Indoline

AbstractA dicarbazolo‐diazocine derivative XIV with the chromophoric system of the toxiferines has been synthesized starting from 4a‐methyl‐l,2, 3, 4‐tetrahydro‐ carbazolenine (V). For two stereoisomeric epoxides XV and XVI which can be isolated besides XIV structures have been established. NMR‐data of XIV, XV and XVI confirm the constitutions given and allow to deduce some details of the steric structure of the three compounds.