Epoxide To diol

Epoxide hydrolase A type of enzyme that converts epoxides to diols by the addition of water. 

Kim, G. J. Park D. W. (2000) The catalytie aetivity of new ehiral salen complexes immobilized on MCM-41 in the asymmetrie hydrolysis of epoxides to diols., Catalysis Today 63 537-547. 

Electrostatic isopotential (EIP) minima186 often identify sites and ease of metabolism by epoxide hydrase, an enzyme responsible for the conversion of epoxides to diols by the addition of water. Molecular electrostatic potential energy calculations also are probably the best means of identifying positions of epoxidation and, possibly, metabolism in general. In the case of aflatoxin B for example, EIP maxima and minima calculated by the CNDO/2 method all lie close to the known sites of metabolism and, in particular, the formation of the carcinogenic 2,3-epoxide is readily predicted.189... 

Nucleophilic Opening. A neutral hydrolysis medium, more effective than water alone is provided by the combination of water and a polar aprotic solvent eg. HMPA or NMP (N-methyl-2-pyrrolidone). Thus 15 aqueous NMP at 130°C containing NaHCO will open terminal (but not internal) epoxides to diols (>90 ) as well as convert haloalkanes to alcohols in high yields. 

Many chemical reactions are catalyzed by acids but on a large-scale can generate significant amoimts of acid waste, which requires neutralization and/ or disposal. In principle, CO dissolved in water is mildly acidic, due to formation of carbonic acid and should be capable of catalyzing a range of reactions. Simple pressure release at the end of the reaction brings the pH back to levels, which require minimal neutralization. Hydrolysis of ketal to cyclohexanone and ethylene glycol and epoxides to diols are a few examples where CO in presence of water have been used as a catalyst [322]. 

Pyrethroids from Chiysanthemic Acid. The unsaturated side chains of the aHethrolone alcohol moieties of the natural pyrethrins are readily epoxidized by microsomal oxidases and converted to diols, thus detoxifying the insecticides. Esterification of chrysanthemic acid (9), R = CH3, with substituted ben2yl alcohols produces usehil insecticides barthrin [70-43-9J, 2-chloro-3,4-methylenedioxyben2yl (+)-i7j ,/n7 j -chrysanthemate, and dimethrin [70-38-2] 2,4-dimethylben2yl (+)-i7j ,/n7 j -chrysanthemate. These have alimited spectmm of insecticidal activity but are of very low mammalian toxicity, ie, rat oralLD s >20,000 mg/kg. 

Although details vary for particular cases, a common synthetic route to diol epoxides such as (30) frequently begins with the ketone (33) (78MI50700). The final epoxidation is often highly stereoselective. A general route to non-K-region arene oxides has been described (75JA3185). 

An oxirane formed by the direct epoxidation, which usually occurs from the sterically least hindered side of the molecule, can be converted into its stereoisomer by a reaction sequence which involves the diaxial opening (in acetic acid at 100° for 2 hr) of the epoxide to a diol mo noacetate. Subsequent mesylation followed by treatment with base gives the inverted oxirane, as shown for the sequence (69) (70) (71) (72). ... 

The reactions of olefins with peracids to form epoxides allows for the selective oxidation of carbon-carbon double bonds in the presence of other functional groups which may be subject to oxidation (for example, hydroxyl groups). The epoxides that result are easily cleaved by strong acids to diols or half-esters of diols and are therefore useful intermediates in the synthesis of polyfunctional compounds. 

Epoxides are cleaved by treatment with acid just as other ethers are, but under much milder conditions because of ring strain. As we saw in Section 7.8, dilute aqueous acid at room temperature is sufficient to cause the hydrolysis of epoxides to 1,2-diols, also called vicinal glycols. (The word vicinal means "adjacent/ and a glycol is a diol.) The epoxide cleavage takes place by SK2-like backside attack of a nucleophile on the protonated epoxide, giving a trans- 1,2-dio) as product. 

Subsequent to the development of the (salen)Cr-catalyzed desymmetrization of meso-epoxides with azide (Scheme 7.3), Jacobsen discovered that the analogous (salen)Co(n) complex 6 promoted the enantioselective addition of benzoic acids to meso-epoxides to afford valuable monoprotected C2-symmetric diols (Scheme 7.15) [26], Under the reaction conditions, complex 6 served as a precatalyst for the (salen) Co(iii)-OBz complex, which was fonned in situ by aerobic oxidation. While the enantioselectivity was moderate for certain substrates, the high crystallinity of the products allowed access to enantiopure materials by simple recrystallization. 

Practical considerations limit, the scalability of this reaction due to the highly reactive and water sensitive intermediates formed. Furthermore, the time required for removal of large amounts of solvent in vacuo allows for the opening of the intermediate epoxide leading to diol formation. 

Chiral epoxides and their corresponding vicinal diols are very important intermediates in asymmetric synthesis [163]. Chiral nonracemic epoxides can be obtained through asymmetric epoxidation using either chemical catalysts [164] or enzymes [165-167]. Biocatalytic epoxidations require sophisticated techniques and have thus far found limited application. An alternative approach is the asymmetric hydrolysis of racemic or meso-epoxides using transition-metal catalysts [168] or biocatalysts [169-174]. Epoxide hydrolases (EHs) (EC 3.3.2.3) catalyze the conversion of epoxides to their corresponding vicinal diols. EHs are cofactor-independent enzymes that are almost ubiquitous in nature. They are usually employed as whole cells or crude... 

The activities of both haloalkanol dehalogenase (halohydrin hydrogen lyase) that catalyzes the formation of epoxides from alkanes with vicinal hydroxyl and halogen groups, and epoxide hydrolase that brings about hydrolysis of epoxyalkanes to diols are involved in a number of degradations that involve their sequential operation. 

The iodocyclization products have a potentially nucleophilic oxygen substituent (3 to the iodide, which makes them useful in stereospecific syntheses of epoxides and diols. 

R,8S)-(+)-Disparlure (12) is the female sex pheromone of the gypsy moth (Lymantria dispar). Advent of Sharpless asymmetric dihydroxylation (AD) allowed several new syntheses of 12 possible. Sharpless synthesized 12 as shown in Scheme 17 [27]. Scheme 18 summarizes Ko s synthesis of 12 employing AD-mix-a [28]. He extended the carbon chain of A by Payne rearrangement followed by alkylation of an alkynide anion with the resulting epoxide to give B. Keinan developed another AD-based synthesis of 12 as shown in Scheme 19 [29]. Mit-sunobu inversion of A to give B was the key step, and the diol C could be purified by recrystallization. 

The diol epoxide derivative of benzo(a)pyrene, trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene also known as (+) -73,8a-dihydroxy-9ot,10a-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene,was the first diol epoxide to be synthesized. Interest in this compound was stimulated by the report by Borgen et al. (8) that a metabolite of benzo(a)pyrene, tentatively identified as the trans-7,8-diol ( 1) became covalently bound to DNA in the presence of rat liver micro-somes. Sims et al. ( ) suggested that the active metabolite was a diol epoxide derivative of unspecified stereo chemistry. 

For the alternant PAH that have been studied extensively, bay-region diol epoxides are important metabolically activated forms. Studies of the chemical and biological activity of a variety of diol epoxides have provided insight into the factors related to reactivity and biological activity. Chemical reactivity, as measured by spontaneous hydrolysis, correlated well with calculated quantum chemical parameters that estimate ir-electron stabilization upon conversion of the epoxide to a benzylic carbocation, provided... 

A Mechanism for the Stereoselectivity and Binding of Benzo[a]pyrene Diol Epoxides to DNA... 

---