2,3-disubstituted oxiranes biohydrolysis

For 2,2-disubstituted oxiranes, this technique was not applicable because an enzyme to perform a highly unfavored nucleophilic attack on a fuUy substituted carbon atom would be required. In this case, a two-step sequence consisting of combined bio- and chemocatalysis was successful (Scheme 2.96) [616]. In the first step, 2,2-disubstituted oxiranes were kinetically resolved by using bacterial epoxide hydrolases in excellent selectivity. The biohydrolysis proceeds exclusively via attack at the unsubstituted carbon atom with complete retention at the stereogenic center. By... 

Only limited data are available on the biohydrolysis of 2,2-disubstituted oxiranes (Fig. 3, Table 3) employing mammalian and yeast epoxide hydrolases. For instance, the presence of a geminal dimetbyl group in 2.1 resulted in complete enantioselectivity when mEH was used as a catalyst. Thus, epoxide 2.1 was resolved to yield the corresponding (/f)-diol and the remaining (5)-epoxide 2.1 both in more than 95% e.e. at 50% conversion. On the other hand, a simple 2-methyl-2-alkyl oxirane such as 2.2 could not be resolved with high efficiency employing mEH. For this substrate pattern, bacterial epoxide hydrolases proved to be extremely useful. 

Another strategy for the achievement of an enantioconvergent process was set up using the combination of bio- and chemo-catalysis[107, 109, 121> 122). For instance, 2,2-disubstituted epoxides were selectively resolved by lyophilized whole cells of Nocardia sp. The biohydrolysis proceeds via attack at the less substituted C-atom with excellent regioselectivity thus leading to retention of configuration at the stereogenic center. On the other hand, acid-catalyzed hydrolysis of such epoxides usually proceeds at the more substituted oxirane carbon with inversion. Careful... 

---