Aromatic and aliphatic epoxides

ALIPHATIC and AROMATIC EPOXIDES see AFM250 ALIPHATIC CHLORINATED HYDROCARBONS see... 

Reactions with aliphatic and aromatic epoxides. The metabolism of many alkenes and arenes Is known to proceed via epoxides formed by phase I reactions (166). Chemical methods for the preparation of epoxides will not be discussed here but valuable references (or references cited therein) for their synthesis are found In Table VII. The electrophilic character of the epoxides has been utilized In chemical synthesis of several PMAF metabolites. Differences In the reactlvltes of arene oxides are probably less Important In chemical synthesis of their conjugates but may Influence the ratio of positional and dlasteromers formed. The reaction of GSH with a xenobiotic epoxide gives the 1,2-dlhydro--l-hydroxy-2-glutathlonyl-xenoblotlc conjugate and with cysteine and N-acetyl-cystelne the corresponding dlhydro-hydroxy conjugates. The nucleophile (GSH, cysteine or N-acetyl-cystelne)... 

Aromatic nitro groups Aromatic rings N-oxides Alkyl hydrazines Alkyl aldehydes N-methyl derivatives Monoalkenes p-Haloethyl mustards N-Chloroamines Alkyl N-nitrosoamines Alkyl esters of either phosphoric or sulfonic adds Aromatic mono- and dialkylamino groups Aromatic azo groups (because of possible reduction to aromatic amines) Aromatic and aliphatic aziridinyl derivatives Aromatic and aliphatic substituted primary alkyl halides Aromatic amines (including their N-hydroxy derivatives and the derived esters Propriolactones and propriosultones Derivatives of urethane (carbamates) Aliphatic and aromatic epoxides... 

Epoxide Ring-opening Reaction. Aluminum trifluoro-methanesulfonate is a remarkably efficient Lewis acid for the ringopening reaction of epoxides by alcohols. Even at ppm levels of the catalyst, various aliphatic and aromatic epoxides reacted with different alcohols in moderate to good yields. 

Cytochrome P-450. Cytochrome P-450 enzymes consist of a large number of haem-containing mono-oxygenases which catalyze aliphatic and aromatic hydroxylations, epoxidations, as well as other oxidation reactions thus, these enzymes are able to cleave aromatic C-H bonds and also... 

Many of the enone substrates used in polyamino acid-catalysed epoxidation reactions can be made via a simple aldol condensation, which leads directly to the desired enone after in situ dehydration. Enones that cannot be synthesised by the above route may often be synthesised using standard Wittig chemistry, (Scheme 6). The above methods of substrate synthesis provide compounds with a variety of groups R and enabling the incorporation of both aliphatic and aromatic moieties into the enone structure. 

The biphasic method, like the triphasic method, allows the epoxidation of a broad range of substrates accommodating both aliphatic and aromatic substituents at either end of the enone moiety. However, unlike the triphasic method, the biphasic conditions allow reaction of hydroxide-sensitive systems. 

For example, epoxides, both aliphatic and aromatic, being chemically unstable are usually potentially reactive metabolites. Quinones and quinoneimines similarly are known to be able to react chemically with endogenous constituents of the cell. 

The relative reactivity of secondary and primary amines with epoxide, k2/kt, can affect the overall kinetics. If k2/kj is not close to 0.5 the parameter f in Eqs. (4-7) and (4-13) becomes significant. In this respect there are differences between aliphatic and aromatic or alicyclic amines. For the aliphatic amines the ratio k2/kj is reported to be in the range 0.6-0.7 83 90), whereas for aromatic amines values in the range 0.2 to 0.5 have been observed 90 9S). For the reaction of BADGE with DDS, Dobas et al. 94) reported a value of 0.21 for k2/k, at 80 °C. This factor is likely to account for part of the observed non-linearity in reduced rate plots at higher levels of conversion. 

A large number of epoxid tions has been carried out with alkaline hydrogen peroxide and a variety of [Pg.356]

Epoxides are involved in the metabolism of many aliphatic and aromatic compounds in plants as well as in mammals. Enzyme potentiality allows both regio- and stereospecific... 

Similarly, preparation of a,a-difluorohomoallylic alcohols has been achieved by zinc-mediated addition of CH2=CHCF2Br to carbonyl compounds.29 The reaction is successful with dialkyl ketones as well as aliphatic and aromatic aldehydes (Equation 4.12). The allylation products are particularly useful since the alkene may be oxidized to an aldehyde,32 epoxide,33 or converted to a 8-lactone34 via hydroformylation. 

Biological systems overcome the inherent unreactive character of 02 by means of metalloproteins (enzymes) that activate dioxygen for selective reaction with organic substrates. For example, the cytochrome P-450 proteins (thiolated protoporphyrin IX catalytic centers) facihtate the epoxidation of alkenes, the demethylation of Al-methylamines (via formation of formaldehyde), the oxidative cleavage of a-diols to aldehydes and ketones, and the monooxygenation of aliphatic and aromatic hydrocarbons (RH) (equation 104). The methane monooxygenase proteins (MMO, dinuclear nonheme iron centers) catalyze similar oxygenation of saturated hydrocarbons (equation 105). ... 

P-450s carry out aliphatic and aromatic hydroxylat-ions, aromatic epoxidations (leading to stable epoxides like dieldrin from aldrin, or arene oxides), 0-, N-, and S-dealkylations and oxidations, oxidative deaminations, and desulfurations among other reactions. Although the primary evolutionary role of the P-450 enzymes is to convert hydrophobic xenobiotics into more hydrophilic compounds and enhance their removal from the body, P-450s also catalyze reactions that lead to more reactive (and hence toxic) compounds. Several xenobiotics are converted into potential carcinogens via the cytochrome P-450 system. 

The NADPH-cytochrome P-450 system, commonly known as the mixed-function oxygenase (MFO) system, is the most important enzyme system involved in the Phase I oxidation reactions. Cytochrome P-450 system, localized in the smooth endoplasmic reticulum of cells of most mammalian tissues, is particularly abundant in the liver. This system contains a number of isozymes which are versatile in that they catalyze many types of reactions including aliphatic and aromatic hydroxylations and epoxidations,... 

The search for improved catalytic systems for epoxide opening reactions has yielded a number of methods to improve this reaction. The use of 10 mol% of Cu(BF )2 has been found to catalyze the ring-opening of epoxides with amines under solvent free conditions <05TL2675>. Both aliphatic and aromatic amines provide excellent yields of the P-amino alcohols. Scandium triflate has also been found to catalyze the ring-opening of epoxides with both aromatic and aliphatic amines in the absence of solvent <05TL9029>. 

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