Enantioselective hydrolysis with

The results actually showed a deracemization of the racemic hydroxyester 10 as opposed to enantioselective hydrolysis with formation of optically pure (R)-hydroxyester 10 and only 20 % loss in mass balance. Small quantities of ethyl 3-oxobutanoate 9 (<5%) were also detected throughout the reaction, leading the authors to suggest a multiple oxidation-reduction system with one dehydrogenase enzyme (DH-2) catalysing the irreversible reduction to the (R)-hydroxy-ester (Scheme 5). 

It is known that the (S)-forms are the essential stereoisomers for the insecticidal activities of both alcohols (4,5). Chemico-enzymatic processes are also reported in this article on the preparation of the optically active pyrethroid insecticides having the (S)-isomers of the two alcohols. Processes were developed that use enantioselective hydrolysis with a lipase. 

Enantioselective Hydrolysis with Arthrobacter Lipase. Reaction performance with the Arthrobacter lipase was studied in detail. The pH profile curve of the zero-order reaction exhibited a pH-optimum around 7.0, and spontaneous hydrolysis was not significant at pH... 

Enantioselective Hydrolysis with Arthrobacter Lipase. The results of the enantioselective hydrolysis of the acetate of racemic CPBA are summarized in Table V for several commercial lipases that liberate very optically pure CPBA. The experimental conditions were chosen to give approximately 50% hydrolysis for each enzyme. It is noticed that all of the lipases in Table V hydrolyzed the ester of (S)-CPBA preferentially to give the insecticidally active (S)-isomer. This is apparently different from the case of HMPC. The highest activity and optical purity were again given by the Arthrobacter lipase. Spontaneous termination of the reaction at 50% hydrolysis was observed with this enzyme as was the case of HMPC. 

Figure 25.2.8 shows the synthetic route to pyriproxyfen. The optical isomer of pyriproxyfen is synthesized using optically active lactic acid as a starter material [46, 47] or by using enantioselective hydrolysis with enzymes [48, 49]. 

PPL and Hpase from Pseudomonas sp. catalyze enantioselective hydrolysis of sulfinylalkanoates. For example, methyl sulfinylacetate (46) was resolved by Pseudomonas sp. Hpase in good yield and excellent selectivity (62). This procedure was suitable for the preparation of sulfinylalkanoates where the ester and sulfoxide groups are separated by one or two methylene units. Compounds with three methylene groups were not substrates for the Hpase (65). 

A very efficient and universal method has been developed for the production of optically pue L- and D-amino adds. The prindple is based on the enantioselective hydrolysis of D,L-amino add amides. The stable D,L-amino add amides are effidently prepared under mild reaction conditions starting from simple raw materials (Figure A8.2). Thus reaction of an aldehyde with hydrogen cyanide in ammonia (Strecker reaction) gives rise to the formation of the amino nitrile. The aminonitrile is converted in a high yield to the D,L-amino add amide under alkaline conditions in the presence of a catalytic amount of acetone. The resolution step is accomplished with permeabilised whole cells of Pseudomonas putida ATCC 12633. A nearly 100% stereoselectivity in hydrolysing only the L-amino add amide is combined with a very broad substrate spedfidty. 

Chiral oxazolidines 6, or mixtures with their corresponding imines 7, are obtained in quantitative yield from acid-catalyzed condensation of methyl ketones and ( + )- or ( )-2-amino-l-phcnylpropanol (norephedrine, 5) with azeotropic removal of water. Metalation of these chiral oxazolidines (or their imine mixtures) using lithium diisopropylamide generates lithioazaeno-lates which, upon treatment with tin(II) chloride, are converted to cyclic tin(II) azaenolates. After enantioselective reaction with a variety of aldehydes at 0°C and hydrolysis, ft-hydroxy ketones 8 are obtained in 58-86% op4. 

Very few optically active cyanohydrins, derived from ketones, are described in the literature. High diastcrcosclectivity is observed for the substrate-controlled addition of hydrocyanic acid to 17-oxosteroids27 and for the addition of trimethyl(2-propenyl)silane to optically active acyl cyanides28. The enantioselective hydrolysis of racemic ketone cyanohydrin esters with yeast cells of Pichia miso occurs with only moderate chemical yields20. 

Another example of reagent-induced asymmetric synthesis is the enantioselective preparation of phosphoramides 6 by addition of dialkylzine reagents to A-diphenylphosphinoylimincs 4 in the presence of the enantiomerically pure 1,2-amino alcohols 5a or 5 b (diethylzinc does not add to A-silyl- or A-phenylimines)12. Phosphoramides 6 (crystalline solids) are obtained in moderate to good yield and good enantioselectivity. The latter can be enhanced by recrystallization. Acidic hydrolysis with dilute 3 M hydrochloric acid/tetrahydrofuran provides the corresponding amines 7 without any racemization. 

K. Adachi, S. Kobayashi, M. Ohno, Chiral Synthons by Enantioselective Hydrolysis of meso-Diesters with Pig Liver Esterase Substrate-Stereoselectivity Relationships , Chi-mia 1986, 40, 311-314. 

Benzyloxy-2-methylpropane-l,2-diol, a desymmetrized form of 2-methylpropane-1,2,3-triol with its terminal hydroxy being protected as a benzyl ether, was prepared using the B. subtilis epoxide hydrolase-catalyzed enantioselective hydrolysis of the racemic benzyloxymethyl-l-methyloxirane readily available from methallyl chloride and benzyl alcohol. The preparation of the racemic epoxide, a key intermediate, was described in Procedures 1 and 2 (Sections 5.6.1 and 5.6.2), its overall yield being 78 %. The combined yield of enantiomerically pure (7 )-3-benzyloxy-2-methylpropane-l,2-diol was 74 % from ( )-benzyloxymethyl-l-methyloxirane, as described in Procedures 3-5 (Sections 5.6.3 and 5.6.5), with the overall procedures leading to the biocatalytic dihydroxylation of benzyl methallyl ether . 

A semi-synthetic metalloenzyme that catalyses the enantioselective hydrolysis of simple amino acid esters has been reported. Iodoacetamido-l,10-phenanthroline (238) was interacted with a cysteine residue in adipocyte lipid binding protein (ALBP) to produce the conjugate ALBP-Phen (239), which was converted into its Cu(II) complex. The ALBP-Phen-Cu(II) was found to catalyse the enantioselective... 

Alternatively, enzymatic resolution of 61 by hydrolysis or of 62 by enzymatic esterification could be achieved with >99% ee and enantioselectivities of E>200, e.g. hydrolysis with common lipases like CAL-B or BCL (Amano PS) [86-88]. Wittig reaction and deprotection led to 64. Enzymatic resolution is also possible at the stage of C15-racemic 65 [86-88]. 

Lipase-mediated enantioselective hydrolysis of an N-unprotected aminoacid ester has been demonstrated with methyl phenylglycinate (Figure 10.9). In the presence of CaLB the E ratio was a rather modest 12, which improved when acetonitrile (ACN) or tert-butyl alcohol was added to the medium and further improved to 34 with 20% [BMIm][BF4] [68, 120]. The addition of more strongly hydrogen-... 

The sex pheromone is interesting from a biosynthetic perspective (see Fig. 4.3) because it is closely connected with primary metabohsm. That is, the monomer 4 is an intermediate in fatty acid biosynthesis. Condensation of acetyl-ACP (8 ACP, acyl carrier protein) with malonyl-CoA (9 CoA, coenzyme A) yields acetoacyl-ACP (10). Enantioselective reduction with NADPH leads to (R)-3-hydroxybutyryl-ACP (11). Two units of this precursor could then be condensed to form the pheromone 5, which then degrades to 4 and 6 as described above. Alternatively, 4 can also be formed by direct hydrolysis of intermediate 11. 

In view of the Zr-catalyzed enantioslective carbomagnesation-elimination tandem reaction of allylic derivatives discussed earlier, a similar process with EtjAl might be expected and has indeed been developed recently [29]. As a representative example, the reaction of 2,5-dihydro-furan with 3 equiv. of Et3Al in the presence of (i )-(EBTHI)Zr[B[NOL-(5)] (8) and (NMTHI)ZrCpCl2 (9) produced, after hydrolysis, (S)-2-ethyl-3-buten-1 -ol in 90 and 67% yields, respectively. The enantioselectivity observed with 8 was >99% ee, whereas that observed with 9 was 85-90% ee. Upon deuterolysis of the organoaluminum products, a mixture of monodeuterated and nondeuterated products was obtained and the extent of D incorporation increased to 94% with neat Et3Al without any solvent. The results indicate that the reaction must produce two organoaluminum products, 10 and 11 (Scheme 4.18). On oxidation with 02 only... 

The enantioselective hydrolysis of the racemic 2-acetoxy-l-silacyclohexane rac-78 represents a further example of an enzymatic kinetic racemate resolution (Scheme 15). Hydrolysis of this compound in the presence of porcine liver esterase (PLE E.C. 3.1.1.1) yielded the optically active 1-silacyclohexan-2-ol (S)-43 which was isolated with an enantiomeric purity of 93% ee7. Similar results were obtained when using a crude lipase preparation from Candida cylindracea (CCL E.C. 3.1.1.3) as the biocatalyst... 

Initial investigations showed that the treatment of trimethylsilyl nitronate 23a (R1 = Me) with benzaldehyde (R2 = Ph) in the presence of (S,S)-6b (X = HF2, 2 mol %) in TH F at —98 °C for 1 h and at —78 °C for 1 h and subsequent hydrolysis with 1M HC1 at 0 °C, resulted in clean formation of the corresponding nitroalkanol 24 (R1 = Me, R2 = Ph) in 83% yield (anti/syn = 74 26) with 33% ee (anti isomer) (entry 1 in Table 9.5). Notably, the poor diastereo- and enantioselectivities were dramatically improved by switching the catalyst to (S,S)-6c (X = HF2) possessing a radially extended 3,3-aromatic substituent (Ar), and 24 (R1 = Me, R2 = Ph) was obtained in 92% yield (anti/syn = 92 8 with 95% ee (anti isomer) (Table 9.5, entry 2). This asymmetric nitroaldol protocol tolerates various aromatic aldehydes to afford anti-nitroaldols selectively, being complementary to Shibasaki s method... 

Antibody-catalyzed reactions, too, can be conducted on a gram scale (Reymond, 1994) the biocatalyst was separated by dialysis in a cellulose membrane (12-14 kDa, antibody 150 kDa) and reused. The enantioselective hydrolysis of the enol ether (4) to the ketone (5) ran with an e.e. of 89-91% (Figure 18.10). 

A characteristic feature of this solid-phase amino acid synthesis is the use of the phosphazene bases 53 and 54 for the PTC alkylation reaction [64, 65]. Because these compounds, which are soluble in organic media, do not react with alkyl halides, both alkyl halide and phosphazene bases can be added together at the start of the reaction, which is useful practically [65], Cinchonine and cinchonidine-derived salts, e.g. 25, were found to be very efficient catalysts. Under optimum conditions the alkylation proceeds with enantioselectivity in the range 51-99% ee, depending on the alkyl halide component [65], Seventeen different alkyl halides were tested. After subsequent hydrolysis with trifluoroacetic acid the corresponding free amino acids were obtained in high yield (often >90%). 

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