Hydrolysis enantiotopically selective

Enantiotopically selective ester hydrolysis can also be achieved enzymatically (Table 8). Eiflier one ester group in a me.ro-diester (103)-(1(M>) or one acetate in a me.m-diacetate (107) 111) are saponified with PLE or other lipases. In favorable cases enzymatic acylation and deacylation are stereochemically complementary and may thus be combined to gain access to bodi enantiomers, as illustrated by the example in Table 9. ... 

In contrast to the hydrolysis of prochiral esters performed in aqueous solutions, the enzymatic acylation of prochiral diols is usually carried out in an inert organic solvent such as hexane, ether, toluene, or ethyl acetate. In order to increase the reaction rate and the degree of conversion, activated esters such as vinyl carboxylates are often used as acylating agents. The vinyl alcohol formed as a result of transesterification tautomerizes to acetaldehyde, making the reaction practically irreversible. The presence of a bulky substituent in the 2-position helps the enzyme to discriminate between enantiotopic faces as a result the enzymatic acylation of prochiral 2-benzoxy-l,3-propanediol (34) proceeds with excellent selectivity (ee > 96%) (49). In the case of the 2-methyl substituted diol (33) the selectivity is only moderate (50). 

As was the case for kinetic resolution of enantiomers, enzymes typically exhibit a high degree of selectivity toward enantiotopic reaction sites. Selective reactions of enaiitiotopic groups provide enantiomerically enriched products. Thus, the treatment of an achiral material containing two enantiotopic functional groups is a means of obtaining enantiomerically enriched material. Most successful examples reported to date have involved hydrolysis. Several examples are outlined in Scheme 2.11. 

Reduction of the achiral ketodiester 139 gives the racemic lactone 140. Hydrolysis of both ester groups then gives the again achiral hydroxydicarboxylate 141. This compound is prochiral and the two C02 groups are enantiotopic. If one could be protonated selectively by an enantiomerically pure acid, one enantiomer of the monoacid would be formed. This sounds like an improbable event. 

Many developments have come from Corey s laboratories in the lactacystin area since the synthesis described above.24 One strategy we have not mentioned before is the use of an enzyme, pig liver esterase (chapter 29) in the selective hydrolysis of one of two enantiotopic ester groups in the malonate 161. An MeS group is used to block enolisation and prevent racemisation of the product 162. The mono ester 162 is initially formed in 67% ee improved by one crystallisation of the quinine salt to 95% ee. The pyrrolidine ring 164 is made in an unusual way by first forming the amide 163 and then cyclising the diester by carbonyl condensation. The new chiral centre in 164 is not controlled but disappears in the next step. 

I, 2-position, seem to be less appropriate substrates for pig liver esterase (33-39 and 41-43). Finally, it seems noteworthy that transition metal complexes containing enantiotopic esters groups are also amenable to a highly selective pig liver esterase-catalyzed hydrolysis (71). Cyclic monoesters of Table 11.1-1, which can be obtained with other hydrolases as such or of opposite configuration, are contained in Tables... 

Some reactions proceed with enantiotopic group selectivity (see appendix) in the sense that a kinetic resolution is coupled to an initial asymmetric reaction. An example is the enzyme-catalyzed partial hydrolysis of achiral meso-diol diacetate esters to chiral, optically pure monoesters (Y.-F. Wang, 1984). The pro-S group of the diacetate is preferentially cleaved by pig pancreatic lipase. The other group is cleaved somewhat more slowly = 15.6). 

The catalyst we will use Is the amino acid L-proline—no derivatization or protection required. It was actually back in 1971 that it was first noted that L-proline will catalyse asymmetric aldols, but until the year 2000 examples were limited to this one cyclization. Treatment of a triketone with proline leads to selective cyclization onto one of the two enantiotopic carbonyl groups. A molecule of proline must condense with the least hindered ketone, and in this case an enamine (rather than an iminium ion) can form. The chiral enamine can select to react with only one of the two other carbonyl groups, and it turns out that it chooses with rather high selectivity the one coloured green in the scheme below. Cyclization, in the manner of a Robinson annelation, and hydrolysis of the resulting iminium ion follow on, releasing the molecule of L-proline to start another catalytic cycle. The isolated product is the bicyclic ketone, in 93% ee. 

Chiral ligand 651 is obtained from the appropriate natural amino-acid phenylalanine, whereas the corresponding derivatives of valine or leucine proved to be slightly less effective [46], Axially prochiral, enantiotopic, biaryl-2,6-diols have been converted to the respective chiral compounds via enzymatic desymmetrization. Thus Pseudomonas cepacia lipase (PCL) catalysed the atropisomerically-selective hydrolysis of diacetate 654 to give monoacetate 655 in 67% yield and 96% e. e. [47], Scheme 24. 

The most important technical applications of catalytic hydrolysis and acylation involve technical enzymes, as used in food processing, washing powders, or derace-misations. Especially the latter application has also found significant application in chemical synthesis. The kinetic resolution of chiral, racemic esters, anhydrides, or alcohols relies on the faster conversion of only one substrate enantiomer by the chiral catalyst, whereas the other enantiomer ideally remains unchanged. A special case within kinetic resolutions is the desymmetrization of prochiral mexo-compounds like mera-anhydrides (2) or meso-diols, (5) that requires a selective conversion of one of the two enantiotopic functional groups (carbonyl or OH-group, Scheme 7.1). 

Nelson has described the resolution reaction of diepoxide 160 to furnish diol 161 in >95 % ee and 98% yield (Scheme 9.19) [134]. This clever desym-metrization of the centrosymmetric diepoxide 160 proceeds by selective hydrolysis of one of the enantiotopic epoxides and provides a key intermediate toward the marine neurotoxin hemibrevetoxin B (162). 

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