2,3-epoxybutane, hydrolysis

Both the mono- and diepoxides of butadiene are substrates for epoxide hydrolase [163], In rat liver microsomes, (R)- and (S)-butadiene monoepoxides were hydrolyzed to but-3-ene-l,2-diol (10.104, Fig. 10.24) with complete retention of configuration at C(2), indicating attack at C(l) [164], In mouse liver microsomes, in contrast, 15 - 25% inversion of configuration was observed, suggesting partial attack at C(2). Preliminary results indicate that human liver microsomes are more efficient than mouse or rat liver microsomes in hydrolyzing butadiene monoepoxide [165]. The hydrolysis of diepoxybutane (10.103) yields 3,4-epoxybutan-l,2-diol (10.105), which can be further hydrated to erytritol (10.106) [163]. 

Parallel to these efforts, an efficient and reliable expression system for ANEH was developed (95). Subsequently, two libraries of mutants were generated by epPCR, comprising 3500 and 4 600 clones, respectively. Mutants were discovered displaying an expression level 3.4 times higher than the original WT and a 3.3-fold enhancement of catalytic activity as measured by the hydrolysis of 4-(p-nitrophenoxy)-1,2-epoxybutane (95). The distribution of ANEH activities from the clones of these two libraries is shown in Fig. 21. 

Stereochemical specificity fe manifest in the reaction of frans-2,3-epoxybutane with acetic acid, which Wjiustein and Lucas reported to give only ryJAre-2-acetoxy-3-butanol (Eq. 746). Hydrolysis leads to optically inactiveme o-2,3-hutanediol. Similarly, Bdeeeken and Cohen1 had described previously the preparation of racemic [Pg.460]

Similar results were described by Mamouhdian and Michael, who isolated 18 bacterial strains able to produce optically enriched epoxides with excellent ee s (up to 98%) [104, 105]. However, in the case of trflns-(2J ,3J )-epoxybutane, it was shown that the enantiomeric enrichment is in fact due to a second-step enantioselective hydrolysis of the epoxide, which is first produced in racemic form. This, interestingly, is an unexpected example of the possible use of microbial epoxide hydrolases for the synthesis of enantiopure epoxides (see below). 

A Ti-O-OH unit is able to form a five membered cyclic structure with a donor hydroxyl moiety coordinated on Ti as represented in the scheme (II). The cyclic structure can produce a significant increase of both stability and acid dissociation. We observed also that the acid activity of TS-I-O2 is solvent dependent. The hydrolysis rate of trans-2-3-epoxybutane decreases in the order CH3OH > CjHgOH > H2O. This behaviour is consistent with the presence of cyclic complexes like ... 

R),3( )-(69 R=CH2Ph) via tosylation and acid hydrolysis. The corresponding trans-epoxybutanes were obtained from the 2(R),3(R)-diol. 

The importance to use optically pure isomers as pharmaceuticals, food additives, agrochemicals, (etc) is becoming more and more evident. The classical resolution still accounts for a large part of chiral production, however the asymmetric synthesis and the use of chiral separation system one becoming increasingly popular. The enantioseletive hydrolytic resolution of racemic epoxides was performed in the ZSM-5/MCM-41 membrane system containing chiral salen complexes. The chiral salen complexes immobilized on the membrane showed a very high enantioselectivity in the hydrolysis of epichlorohydrine, epoxybutane, styrene oxide and 1,2-epoxyhexane. 

Both enantiomers of 4-iodo-1,2-epoxybutane are available from ( S)-malic acid as shown in Schemes 57 and 58. Reduction of THP-protected dimethyl or diethyl malate with lithium aluminum hydride gives diol 417. Immediate mesylation affords 418 in 65—70% overall yield [6,19]. Acidic hydrolysis of the THP ether furnishes the crystalline bis-mesylate 419, which upon mild base treatment cyclizes to epoxide 420 with retention of configuration. Treatment with sodium iodide gives (5)-( — )-4-iodo-1,2-epoxybutane (421). 

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