Monoesters and Lactones

Due to the minimal steric hindrance at the (i-carbon atom, esters and lactones with an exo-methylenic double bond are more often accepted, even though examples in the literature are still quite rare. It must be mentioned that in the bioreduction of an a-methylenic lactone with isolated OYEs, isomerization was also observed [112]. 

Also substituted a-chloro and a-bromocinnamates, such as 101, have been shown to undergo reduction with high conversions and ee values, with both baker s yeast and isolated ene reductases, to allow the preparation of several valuable non-natural D-phenylalanines [120]. Indeed, the range of applications of non-natural amino adds is extremely wide (see Chapter 13 for further details). 

Instead, the results of the bioreduction of a-fluoro and a-iododnnamates were disappointing, since the former was not converted at aU, while with the latter the enantioselectivity was considerably lower [107]. Overall, after a comprehensive analysis of the observed trends, it can be conduded that a suitable suhstitution pattern can very effectively tune the reactivity of the C=C hond of unsaturated esters. However, although the best candidates for preparative bioreductions could be sorted out easily, electronic and steric effects could not be disentangled, thus preventing general statements on the specific interactions (and stereochemical outcome) involved with a given substrate [107]. 

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Asymmetric ring opening of achiral monocyclic, bicyclic and tricyclic anhydrides under formation of the corresponding chiral monoesters can be accomplished in high yield with modest enantioselectivity with methanol in the presence of less than stoichiometric amounts of cinchona alkaloids in toluene or diethyl ether (Table 9)91 94. As expected the use of cinchonine A or quinidine C, and of cinchonidine B or quinine D gives opposite enantiomers. Recrystallization of the monoesters and lactones affords material of considerably higher enantiomeric purity (Table 9, entries 15, 16, 21, and 23). 

Acids, monoesters and lactones of Table 11.1-13 which can be obtained with other hydrolases as such or of opposite configuration are contained in Table 11.1-5. 

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