METHYLOXIRANES, ENANTIOMERIC

Bacillus subtilis, engineered to overproduce epoxide hydrolase, was used as a whole-cell biocatalyst to resolve racemic 1-benzyloxymethyl-1-methyloxirane with high (5)-selectivity. The remaining (/ )-epoxide was subsequently ring opened in situ, with inversion of stereochemistry, to obtain highly enantiomerically enriched (/ )-3-benzyloxy-2-methylpropane-l,2-diol in greater than 50 % theoretical yield (Figure 5.2). 

Benzyloxy-2-methylpropane-l,2-diol, a desymmetrized form of 2-methylpropane-1,2,3-triol with its terminal hydroxy being protected as a benzyl ether, was prepared using the B. subtilis epoxide hydrolase-catalyzed enantioselective hydrolysis of the racemic benzyloxymethyl-l-methyloxirane readily available from methallyl chloride and benzyl alcohol. The preparation of the racemic epoxide, a key intermediate, was described in Procedures 1 and 2 (Sections 5.6.1 and 5.6.2), its overall yield being 78 %. The combined yield of enantiomerically pure (7 )-3-benzyloxy-2-methylpropane-l,2-diol was 74 % from ( )-benzyloxymethyl-l-methyloxirane, as described in Procedures 3-5 (Sections 5.6.3 and 5.6.5), with the overall procedures leading to the biocatalytic dihydroxylation of benzyl methallyl ether . 

R)-ALKYLOXIRANES OF HIGH ENANTIOMERIC PURITY FROM (S)-2-CHL0R0ALKAN0IC ACIDS VIA (S)-2-CHL0R0-I-ALKAN0LS (R)-METHYLOXIRANE (Oxirane, Bethyl- (R)-)... 

Figure 3. Analytical enantiomeric separation of methyloxirane on EU-CAM3 by complexa-tion GC (center). Racemic sample spiked with (Rj-enantiomer (left) and with (S)-enantiomer (right). Experimental conditions cf. text. (R -methyloxirane elutes after 9 min (Golding et al., 1977).

Koppenhoefer, B. Schurig, V. (R)-Alkyloxi-ranes of high enantiomeric purity from (S)-2-chloroalkanoic adds via (S)-2-chloro-l-alka-nols (R)-methyloxirane. Org. Synth. 1993, Coll. Vol. VIII, 434—+41. 

OPTICALLY ACTIVE EPOXIDES FROM VICINAL DIOLS VIA VICINAL ACETOXY BROMIDES THE ENANTIOMERIC METHYLOXIRANES... 

It took another 35 years until the first (and still the only known) enantioselective total synthesis of (/ )-ochratoxin a (326), and therefore of ochratoxins A and B, was published by Gill et al. in 2002 (264, 265). Scheme 6.1 shows six steps of the nine-step synthesis, which was achieved with 10% overall yield. The first three steps of the procedure are not shown and comprise the preparation of 327 from (/ )-2-methyloxirane according to ref. (266). Ketene dimethyl acetal and acetylenic ester 327 react in an intermolecular cycloaddition to give 328. This diene undergoes a Diels-Alder reaction with methyl propiolate to yield 329. Lactonization ( 330), demethylation ( 331), chlorination ( 332), and methyl ester cleavage finally furnished enantiomerically pure ochratoxin a (326) (267). 

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