Chiral carboxylic acids, enzymatic

The synthesis of chiral carboxylic acids by enzymatic resolution of the corresponding racemate is a widely established method, and for this purpose a broad variety of esterases are commercially available. Consequently, this... 

Several current efforts are focusing on the portability of enzymatic heterocyclization. For example, novel chiral heterocyclic carboxylic acids were produced by using hybrid enzymes [62] (Figure 13.21). Stimulated by biosynthesis pathways, biomimetic heterocyclization methods have also been developed with high efficiency [63]. 

The second chirality source used in the synthesis of aminocyclopropane carboxylic acids was D-glyceraldehyde acetonide, which after Wittig-Homer-Emmons reaction provided the alkenes 61. Treatment with diazomethane and subsequent irradiation at low temperatures alforded the cyclopropanes 62, which were converted into several other derivatives by modification of the side chain (Scheme 11). Notably, the best results were obtained by irradiating in the presence of benzophenone as triplet sensitizer [33, 34]. Following a similar synthetic procedure allocoronamic acid 65 was prepared, which is one of the amino acids that can be processed by plant tissues and promises the possibility to control the enzymatic processes underlying plant growth and fruit ripening [35]. 

Patel. R.N.. Banerjee.A., Nanduri, V., Goldberg. S.. Johnston. R.. Hanson, R., McNamee, C., Brzozowski. D.. Tully. T.. Ko. R.. LaPorte. T.. Cazzulino, D., Swaminathan, S.. Parker. L.. and Venit. J. (2000) Biocatalytic Preparation of a Chiral Synthon for a Vasopeptidase Inhibitor Enzymatic Conversion of bP- N-[(Phenylmethoxy)carbonyl]L-homocysteinyl]-L-lysine (1>1 )-disulfide to [4B-(4a.7a,10ab)]l-Octahydro-5-oxo-4-[(phenyl-methoxy) carbonyl]amino]-7H-pyrido-[2.1-b][l 3]thiazepin-7-carboxylic Acid Methyl Ester by a Novel S-Lysine a-Amino-transferase. Enzyme Microb. Technol. 27,376-389. 

A similar dependence of the configuration of the product on the ( /Z)-configu-ration of the substrate was observed during the yeast-mediated reduction of 2-chloro-acrylate esters [1016]. Whereas the chiral recognition of the (Z)-alkenes was perfect, the (Ej-isomers gave products with lower e.e. In addition, it was shown that the microbial reduction took place on the carboxylic acid stage, which were formed enzymatically by hydrolysis of the starting esters prior to the reduction step [1017] (Scheme 2.138). 

The hydrolysis of carboxylic acid derivatives using a DKR-based approach is not hmited to cyclic carhonyl compounds as exemplified in Scheme 5.6. For example, when an acyclic racemic thioester (possessing an electron-withdrawing arylsulfanyl group at the a-position) is subjected to enzymatic resolution, hydrolysis occurs smoothly to give the chiral carboxylic acid in high enantiomeric excess... 

R.N. Patel, A. Banerjee, V. Nanduri, S. Goldberg, R. Johnston, R. Hanson, C. McNamee, D. Brzozowsld, T. Tully, R. Ko, T. LaPorte, D. Cazzulino, S. Swaminathan, L. Parker, J. Venit, Bio-catalytic preparation of a chiral synthon for a vasopeptidase inhibitor Enzymatic conversion of N2- N-[(phenylmethoxy) carbonyl] L-homocysteinyl]-Dlysine (1 > l )-disulfide to [4S-(4a, 7a, 10ab)]l-octahydro-5- oxo-4- [(phenylmethoxy) carbonyl]amino]-7H-pyrido-[2,l-b] [l,3]thiazepin-7-carboxylic acid methyl ester by a novel Dlysine e — aminotransferase. Enzyme Microb. Technol. 27 (2000) 376-389. 

Tetrahydroisoquinolines bearing a chiral center at the Cl position constitute a structural motif found in many biologically active compounds. For instance, (5)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-l-carboxylic acid 114 is a precursor of the natural product (5)-calycotomine (Scheme 57.31). Kanerva, Fiilbp, et al. have described the preparation of both enantiomers of 114 by enzymatic hydrolysis of the ethyl ester derivative rac-113. Considering this substrate undergoes spontaneous racemization in an aqueous medium, these authors carried out an exhaustive study of the reaction variables in order to find the optimal conditions and thus achieve the DKR of this substrate. Two enzymes with opposite enantiopreferences were used CAL-B and... 

Aziridine carboxylates are chiral intermediates for the synthesis of -lactams and amino acids [200]. The use of enantioselective ester hydrolysis in the synthesis of optically active A -unsubstituted and A-substituted aziridine carboxylate by Candida cylindraceae lipase has been demonstrated by Bucciareli et al. [199]. Racemic methyl aziridine-2-car-boxylate and 2,3-dicarboxylate 110 were used as substrates both for enzymatic hydrolysis and for the synthesis of AAchloro, iV-acyl and A-sulfonyl derivatives (Fig. 38). The reaction yield of 35-45% (theoretical maximum yield is 50%) and the e.e. s of 90-98% were obtained depending on substrate used in the reaction mixture. 

Applications of peroxide formation are underrepresented in chiral synthetic chemistry, most likely owing to the limited stability of such intermediates. Lipoxygenases, as prototype biocatalysts for such reactions, display rather limited substrate specificity. However, interesting functionalizations at allylic positions of unsaturated fatty acids can be realized in high regio- and stereoselectivity, when the enzymatic oxidation is coupled to a chemical or enzymatic reduction process. While early work focused on derivatives of arachidonic acid chemical modifications to the carboxylate moiety are possible, provided that a sufficiently hydrophilic functionality remained. By means of this strategy, chiral diendiols are accessible after hydroperoxide reduction (Scheme 9.12) [103,104]. 

The most prominent cellulose ester produced on the industrial scale is cellulose acetate. The reaction is usually performed with acetic anhydride and with sulfuric acid as a catalyst. To minimize heterogeneities, acetylation is allowed to run nearly to completion, and subsequently partial ester hydrolysis is initiated by the addition of water until a desirable solubility is achieved that corresponds to a DS of about 2.5. Such higher acyl homologues as propanoyl or butanoyl exhibit more thermoplastic properties. Many specialized esters such as chiral (-)-menthyloxyacetates, furan-2-carboxylates, or crown-ether-containing acylates have been prepared on the laboratory scale and characterized by NMR spectroscopy. Various procedures have been applied, using anhydrides and acyl chlorides as acylating agents in combination with such bases as pyridine, 4-dimethylaminopyridine (DMAP), or iV,iV -carbonyldi-imidazole. The substitution pattern of cellulose acetates has also been modified by postchemical enzymatic deacetylation. Cellulose 6-tosylates have been used as activated intermediates for nucleophihc substitution to afford 6-amino-6-deoxy, 6-deoxy, or 6-deoxy-6-halo-celluloses. ... 

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