Selectivity enhancement of epoxide hydrolase catalyzed resolution of 2,2-disubstituted oxiranes by substrate modification

A series of (+/-)-2,2-disubstituted oxiranes bearing an alkene or alkyne fu nctional group were resolved by bacterial epoxide hydrolases with excellent selectivities. The presence of a carbon-carbon double or triple bond furni shed a highly flexible system for substrate modification, which allowed the enantioselectivity to be tuned by rational substrate modification. Thus, a significant selectivity enhancement of more than a ten-fold increase of E- values was achieved by appropriate choice of the C-C multiple bond, i.e. by (i) choosing an alkene or alkyne moiety or by (ii) variation of the E/Z-co nfiguration of olefinic substrates. The enantioenriched epoxides and vicina l diols thus obtained may be easily transformed into omega -functionalized building blocks containing a chiral fully substituted carbon atom by oxidat ive cleavage of the carbon-carbon multiple bond.