Epoxidation chemoenzymatic

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]. 

It should also be mentioned that chemoenzymatic epoxidation reactions have been proposed using lipase and H2O2 on multigram scale [120]. 

With respect to the methods described above, chemoenzymatic epoxidation gained much interest as it does not show any undesired ring opening of the oxir-... 

Scheme 12.3 Chemoenzymatic generation of the peroxycarboxylic acid and subsequent epoxidation of the fatty material.

Orru, R.V.A., Mayer, S.F., Kroutil, W. and Faher, K., Tetrahedron, Chemoenzymatic deracemi-sationof (+)-2,2-disubstituted oxiranes. 1998, 54, 859. Steinreiber, A., Hellstrdm, H., Mayer, S.F., Orru, R.V.A., Faber, K., Chemo-enzymatic enantio-convergent synthesis of C4-huilding blocks containing a fully substituted chiral carbon center using bacterial epoxide hydrolases. Synlett, 2001, 111. 

Scheme 15. Chemoenzymatic synthesis of a-bisabolol using fungal epoxide hydrolase...

Epoxide hydrolases are less used than lipases however, in recent years the synthesis of chiral diols with these biocatalysts has emerged as an excellent methodology to develop new and interesting chemoenzymatic processes [13],... 

A simple, divergent, asymmetric synthesis of the four stereoisomers of the 3-amino-2,3,6-trideoxy-L-hexose family was proposed by Dai and coworkers [222], which is based on the Katsuki-Sharpless asymmetric epoxidation of allylic alcohols (Scheme 13.115). Recently, A-trifluoroacetyl-L-daunosamine, A-trifluoroacetyl-L-acosamine, A-benzoyl-D-acosamine and A-benzoyl-D-nistosamine were derived from methyl sorbate via the methyl 4,5-epoxy-( -hex-2-enoates obtained via a chemoenzymatic method [223]. 

Kiaas, M. R., Warwei, S. Chemoenzymatic Epoxidation of Aikenes by Dimethyl Carbonate and Hydrogen Peroxide. Org. Lett. 1999,1, 1025-1026. 

Fig. 8. Chemoenzymatic synthesis of chiral epoxides via the a-haloketone reduction route...

A few synthetic applications for obtaining biologically active compounds have been described, based on the use of these bacterial enzymes. For instance, the pheromone (S)-frontalin was synthesized in five steps in 94% ee (but rather low overall yield) via a chemoenzymatic route implying epoxide resolution using lyophilized cells oi Rhodococcus equi [189] (Fig. 16). 

Fig. 16. Bacterial epoxide hydrolase. Key steps of chemoenzymatic synthesis of (S)-frontalin...

Fig. 22. Fungal epoxide hydrolysis. Chemoenzymatic synthesis of (S)-2-methyl-heptene oxide [149]...

Linear unsaturated and epoxidized polyesters via enzymatic polymerization were reported as well [58]. For this long-chain symmetrically unsaturated a,co-dicarboxylic acid dimethyl esters (C18, C20, C26) were synthesized using metathesis techniques from 9-decanoic, 10-undecanoic, and 13-tetradecanoic acid methyl esters, respectively. The dicarboxylic acid dimethyl esters were epoxidized via chemoenzymatic oxidation with hydrogen peroxide/methyl acetate and Novozym... 

Finally, a chemoenzymatic enantioconvergent procedure led to (S)-ibuprofen in four steps and 47% overall yield (Fig. 11.2-20). The latter compound is a widely used antiinflammatory drug and pain remedy and is one of the top ten drugs sold worldwide l,HH. In the key step, the conditions for the enantioconvergent hydrolysis of para-iso-butyl-a-methylstyrene oxide was optimized (elevated substrate concentration at +4 °C) to afford the non-reacted epoxide in >95 % ee[136l After separation from the epoxide, the formed diol (70% ee) was recycled via a two-step sequence via the corresponding bromohydrin, which was cyclized back to give ( )-epoxide. The latter material was subjected to repeated biocatalytic resolution in order to improve the economy of the process. 

Riisch gen. Klaas, M., and S. Warwel, Chemoenzymatic Epoxidation of Unsaturated Fatty Acid Esters and Plant Oils, J. Am. Oil Chem. Soc. 73 1453-1457 (1996). 

Fig. 3. Chemoenzymatic self- epoxidation of unsaturated fatty acids reaction principle.

Fig. 5. Chemoenzymatic epoxidation of unsaturated fatty alcohols with ethylbutyrate vs. diethylcarbonate as the peroxy acid source.

From Achiral Non-carbohydrates. - Epoxide 57, available from methyl sorbate by a chemoenzymatic synthesis (Ono et ai, Tetrahedron Asymmetry, 1996, 7, 2595), was used in the construction of a set of isomeric 3-amino-2,3,6-trideoxyhexoses. Addition of benzylamine to the a,p-unsaturated add moiety before or after opening of the epoxide ring led to the D-acosamine derivative 58 or the lactone 59, respectively (Scheme 17)." Lactone 59 has previously been converted to L-daunosamine and D-acosamine derivatives (Vol. 14, p. 72, ref. 14). 

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