Saponification, enantioselective

ENANTIOSELECTIVE SAPONIFICATION WITH PIG LIVER ESTERASE (PLE) (1S,2S,3R)-3-HYDROXY-2-NITROCYCLOHEXYL ACETATE... 

Several review articles containing discussions of enantioselective syntheses with ester-cleaving enzymes have appeared recently (as of 1987).9 13 Of the many examples, the ones in which meso-substrates are employed are most attractive since the theoretical yield is 100%. In many applications of PLE the enantiomeric excess (% ee) of the product depends crucially upon the source of the enzyme. This effect has not been noticed in the enantioselective saponifications of nitrodiol diacetates, either because the reaction is insensitive to it, or because this complication is overcome by the great crystallization tendency of the products. The only problem we observed when the reaction was carried out with commercial crude PLE-powder (but not with the self made one) was the production of a certain amount of diol which could not be removed by simple recrystallization. In this case, filtration over a short silica gel column with methylene chloride as eluent gives after recrystallization pure monoacetate. 

Eberle, M. Missbach, M. Seebach, D. Enantioselective saponification with pig liver esterase (lS,2S,3R)-3-hydroxy-2-nitrocyclo-hexyl acetate. Org. Synth. 1993, Coll. Vol. VIII, 332-338. 

Enantioselective Saponification with Pig Liver Esterase (PLE) (lS,2S,3R)-3-Hydroxy-2-nitrocyclohexyl Acetate M. Eberle, M. Missbach, and D. Seebach,... 

Enantioselective saponification of an achiral complexed diester using pig fiver esterase as chiral reagent. 

Continuing the synthesis of rac-6 with enantiomerically pure diols 12 and ent-l2 (after saponification of 15 with KOH), both enantiomers 6 and ent-6 were accessible. This allowed for an enantioselective synthesis of natural kel-soene (1) and its enantiomer (ent-l) (see below) with only one additional step as compared to the synthesis of the racemate (rac-l). 

Alternatively, enantioselective intramolecular photocycloisomerizations result from the use of hydroxy acids as chiral tethers, as illustrated in the conversion of 3-oxocyclohexenylcarboxylate 51 to the tricyclic lactone 52 which proceeds with 94% ee [67]. The chiral tether can be recycled by saponification to 53 and this hydroxyacid again converted to lactone 54 without loss of optical purity. 

The first enantioselective total synthesis of (+)-macbecin I was accomplished by R. Baker and co-workers. A key vinyl iodide precursor was prepared stereoselectively using the malonic ester synthesis. Diethyl methylmalonate was treated with in situ generated diiodocarbene in ether at reflux to afford diiodomethylmethylmalonate in good yield. This dialkylated malonic ester then was converted to ( )-3-iodo-2-methyl-2-propenoic acid by reacting it with aqueous KOH. The saponification was accompanied by a concomitant decarboxylation. 

Kawana et al. used xylofuranose derivates as chiral auxiliaries [7, 13], Through its primary hydroxy function, the auxiliary was loaded to the polystyrene resin. Esterification of the immobilized auxiliary 8 gave a-keto esters. Subsequent nucleophilic additions of Grignard reagents afforded resin-bound a-hydroxy esters. Subsequent saponification afforded the chiral a-hydroxy acids 9 (Scheme 12.5) in 18-84% yields and 36-65% enantiomeric excesses. The recovered polymer supported chiral auxiliaries could be reused without decrease of enantioselectivity. 

The diastereofacial selectivity of arylcarbenes has rarely been studied however, there are two reports dealing with enantioselective arylcarbene transfer. Addition of 9-diazofluorene to 2-propenoates or ( )-butendioates, which bear (—)-menthyl or (—)-8-phenylmenthyl groups as optically active auxiliaries, provides cyclopropanecarboxylates with moderate to very good diastcrcoselcctivities9. The best results are obtained with bis(8-phenylmenthyl) ( )-butene-dioate which affords the spiro compound with a d.r. of 95 5. Subsequent saponification and esterification with diazomethane leads to the corresponding spiro ir s[2,3]bis(methoxycarb-onyl)cyclopropane-l,9 -[9/f]-fluorene with 85% ee. 

The first highly enantioselective cross-aldol-Tishchenko reaction of alkyl aryl ketones 28 and aldehydes was developed by the group of Shibasaki et al. [15]. With a chiral heterobimetallic lanthanide-based catalyst, this reaction was shown to proceed in typically very good enantioselectivity to furnish, after saponification of... 

Hiyama et al. have reported an enantioselective synthesis of p-hydroxy 5-lactones as simplified analogs of compactin and mevinolin [47] (Scheme 10). The p,5-diketo ester 54 derived from Taber s chiral alcohol 57 was subjected to a stereoselective reduction with sodium borohydride in the presence of Et2BOMe to afford a syn diol, which upon saponification and then heating in dry toluene led to the chiral lactone 56. 

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