Oxiranes, hydrolysis

Infrared studies were also made on several vernonia oil samples, see Figure 2. The epoxy absorption is at 825 cm (18 a,b), Attention is drawn to the hydroxyl absorption band at 3800 cm The data obtained to date indicate that the oxirane band is essentially constant with time, while the hydroxyl absorption (of the order of 5% hydroxyls) increases somewhat with the age of the samples and/or exposure to atmospheric oxygen or water. Thus, the change in the hydroxyl absorption is probably not due to oxirane hydrolysis, but may be due to some oxidation reaction involving the unsaturation of the fatty acid. Perhaps the type of oxidation... 

Besides direct hydrolysis, heterometaHic oxoalkoxides may be produced by ester elimination from a mixture of a metal alkoxide and the acetate of another metal. In addition to their use in the preparation of ceramic materials, bimetallic oxoalkoxides having the general formula (RO) MOM OM(OR) where M is Ti or Al, is a bivalent metal (such as Mn, Co, Ni, and Zn), is 3 or 4, and R is Pr or Bu, are being evaluated as catalysts for polymerization of heterocychc monomers, such as lactones, oxiranes, and epoxides. An excellent review of metal oxoalkoxides has been pubUshed (571). 

Many functional groups are stable to alkaline hydrogen peroxide. Acetate esters are usually hydrolyzed under the reaction conditions although methods have been developed to prevent hydrolysis.For the preparation of the 4,5-oxiranes of desoxycorticosterone, hydrocortisone, and cortisone, the alkali-sensitive ketol side chains must be protected with a base-resistant group, e.g., the tetrahydropyranyl ether or the ethylene ketal derivative. Sodium carbonate has been used successfully as a base with unprotected ketol side chains, but it should be noted that some ketols are sensitive to sodium carbonate in the absence of hydrogen peroxide. The spiroketal side chain of the sapogenins is stable to the basic reaction conditions. 

A higher glycol yield (approximately 94%) than from the ethylene oxide process is anticipated. However, there are certain problems inherent in the Oxirane process such as corrosion caused hy acetic acid and the incomplete hydrolysis of the acetates. Also, the separation of the glycol from unhydrolyzed monoacetate is hard to accomplish. 

The enantioconvergent biohydrolysis of sterically demanding trisubstituted oxiranes has also been reported [189,190]. For instance, the enantioconvergent hydrolysis of a trisubstituted rac-epoxide (Figure 6.70) was a key step in the chemoenzymatic synthesis of a volatile constituent of the beer aroma [190]. 

Reductive opening of the oxirane ring of 193 with lithium aluminum hydride, and acetylation, provided compound 194. Epoxidation of 194 with mCPB A gave the epoxide 195. Opening of the oxirane ring with acetate ions, followed by acetylation, gave the tetraacetate 196, or, by exhaustive acetylation with acetic anhydride-DMAP, the pentaacetate 189. Compounds 196 and 189 were readily transformed into 190 by hydrolysis. " ... 

Carbonyl compounds, such as aldehydes [103, 179], (thio)ketones [31, 94, 180-183], carboxylic acids, and esters [183, 184] with 1 are reduced to alcohols after hydrolysis [5], except in stericaUy hindered cases (see Section 8.5) [185, 186]. Under the same experimental conditions the regioselective reduction of the oxirane ring with 1 gives also the corresponding alcohol [183, 187]. 

When 1,2-diols are subjected to the same reaction conditions required for the formation of sulphonic esters, oxiranes are produced [27]. Presumably, the mono ester is initially formed and, under the basic conditions, intramolecular elimination occurs to produce the oxirane. Partial hydrolysis and ring-closure of a,p-di(tosyloxy) compounds under basic phase-transfer catalytic conditions provides a convenient route to carbohydrate oxiranes [e.g. 28, 29]. Oxiranes have been produced by an analogous method via carbonate esters from partially protected carbohydrates [30],... 

S )-enantiomer to form the (S)-diol, in contrast to the behavior of higher al-kyloxiranes (see above). However, 2-(7er/-bu(yl )oxirane (10.41, R = /-Hu) confirmed a faster hydrolysis of the (R)-enantiomer, but this was shown to be due to complex inhibitory effects. 

An unusual case of intramolecular competition (chemoselectivity, see Chapt. 1 in [la]) between ester and oxirane occurs in the detoxification of (oxiran-2-yl)methyl 2-ethyl-2,5-dimethylhexanoate (10.49), one of the most abundant isomers of an epoxy resin. The compound is chemically very stable, i.e., resistant to aqueous hydrolysis, but is rapidly hydrolyzed in cytosolic and microsomal preparations by epoxide hydrolase and carboxylesterase, which attack the epoxide and ester groups, respectively [129], The rate of overall enzymatic hydrolysis was species dependent, decreasing in the order mouse > rat > human, but was relatively fast in all tissues examined (lung and skin as portals of entry, and liver as a further barrier). In mouse and rat lung microsomes, ester hydrolysis was 3-4 times faster than epoxide hydration, whereas the opposite was true in human lung microsomes. 

Cleavage of the oxirane C-0 bond produces a zwitterionic intermediate (Fig. 10.22), which that can undergo chloride shift (Pathway a) to 2,2-dich-loroacetyl chloride (10.90) followed by hydrolysis to 2,2-dichloroacetic acid (10.91). Furthermore, the zwitterionic intermediate reacts with H20 or H30+ (Pathway b) by pH-independent or a H30+-dependent hydrolysis, respectively. The pH-independent pathway only is shown in Fig. 10.22, Pathway b, but the mechanism of the H30+-dependent hydrolysis is comparable. Hydration and loss of Cl, thus, leads to glyoxylyl chloride (10.92), a reactive acyl chloride that is detoxified by H20 to glyoxylic acid (10.93), breaks down to formic acid and carbon monoxide, or reacts with lysine residues to form adducts with proteins and cytochrome P450 [157], There is also evidence for reaction with phosphatidylethanolamine in the membrane. 

Isopropenyl)oxirane (10.113, Fig. 10.26) and 2-methyl-2-vinyloxirane (10.114) were hydrolyzed by EH to the corresponding diols (10.116 and 10.117, respectively). Nucleophilic ring opening took place at the less-hindered, unsubstituted C-atom, with retention of configuration at C(2). (2R)-2-(Isopropenyl)oxirane was a better substrate than the (25)-enantiomer. Substrate enantioselectivity was more modest in the hydration of 2-methyl-2-vin-yloxirane (10.114), since this compound is chemically more reactive and undergoes partly nonenzymatic hydrolysis. 

A postulated mechanism for nucleophilic attack in enzymatic hydrolysis suggests that electron-withdrawing substituents on the phenyl ring must accelerate the reaction. This is seen in Table 10.1 when comparing 2-phenyl-oxirane with 2-(4-nitrophenyl)oxirane. A systematic study of a few aryl-substituted phenyloxiranes confirmed this inference [175],... 

In the pH range of 5 - 10, H20-catalyzed hydrolysis is the predominant mechanism (see Fig. 10.11, Pathway b), resulting in the formation of the (8R,9R)-dihydrodiol (10.133, Fig. 10.30). Thus, aflatoxin B1 exo-8,9-epoxide is possibly the most reactive oxirane of biological relevance. Such an extreme reactivity is mostly due to the electronic influence of 0(7), as also influenced by stereolectronic factors, i.e., the difference between the exo- and endo-epoxides. The structural and mechanistic analogies with the dihydro-diol epoxides of polycyclic aromatic hydrocarbons (Sect. 10.4.4) are worth noting. 

G. Bellucci, C. Chiappe, F. Marioni, M. Benetti, Regio- and Enantioselectivity of the Cytosolic Epoxide Hydrolase-Catalysed Hydrolysis of Racemic Monosubstituted Alkyloxiranes ,./. Chem. Soc., Perkin Trans. 1 1991, 361 - 363 G. Bellucci, C. Chiappe, L. Conti, F. Marioni, G. Pierini, Substrate Enantioselection in the Microsomal Epoxide Hydrolase Catalyzed Hydrolysis of Monosubstituted Oxiranes. Effects of Branching of Alkyl Chains ,./. Org. Chem. 1989, 54, 5978 - 5983. 

The above-mentioned facts have important consequences on the stereochemical outcome of the kinetic resolution of asymmetrically substituted epoxides. In the majority of kinetic resolutions of esters (e.g. by ester hydrolysis and synthesis using lipases, esterases and proteases) the absolute configuration at the stereogenic centre(s) always remains the same throughout the reaction. In contrast, the enzymatic hydrolysis of epoxides may take place via attack on either carbon of the oxirane ring (Scheme 7) and it is the structure of the substrate and of the enzyme involved which determine the regioselec-tivity of the attack [53, 58-611. As a consequence, the absolute configuration of both the product and substrate from a kinetic resolution of a racemic... 

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