Hydrolysis, selective enzymatic

An enantio-selective enzymatic hydrolysis of meso( )-2,5-diacetoxy-3-hexene gives (+)-( )-(25 ,5/ )-5-acetoxy-3-hexen-2-ol in 77% yield (92% ee).97 The monoacetate with its two allylic groups offers possibilities for stereo-controlled introduction of nucleophiles via Pd(0) catalysis. Synthesis of both enantiomers of the Carpenter bee pheromone based on this strategy is presented in Scheme 5.14.98... 

Selective enzymatic hydrolysis 148 Observing exchangable protons... 

Selective enzymatic hydrolysis. The traditional strategy in sequence determination is to cut protein chains into smaller pieces which can be separated by chromatography or electrophoresis and sequenced individually. Enzymatic cleavage is especially useful because of its specificity. Trypsin, a so-called endo-... 

Tsumura, K., Kugimiya, W., Bando, N., Hiemori, M., Ogawa, T. 1999. Preparation of hypoallergenic soybean protein with processing functionality by selective enzymatic hydrolysis. Food Sci Technol Res 5 171-175. 

Recently, a highly selective enzymatic hydrolysis of racemic 2-azobicy-clo[2.2.1]hept-5-en-3-one has been developed by Chirotech [103]. The selective hydrolytic cleavage of the (+)-lactam led to the desired, unhydrolyzed (-)-enan-tiomer with a high ee of > 98 %. The single (-)-enantiomer (42) functions as an intermediate in the synthesis of the Glaxo Wellcome anti-HIV drug Abacavir (Scheme 25). It is noteworthy that this process operates at a substrate concentration of > 500 g/1. 

A last example is more useful. When the acid moiety in 1.79 reacted with the phosphoryl azide shown, at C, rearrangement occurred to convert the -CO2H moiety into a -NHCO2H moiety. This amino acid [3-amino-2-phenyIpropanoic acid] was trapped as the 4-methylbenzyloxy carbamate 1.80) shown. For the synthesis of amino acids, this approach requires the preparation of half-esters of dicarboxylic acids. There are several methods known to do this, including selective enzymatic hydrolysis. Where the half-ester is available, this is a good synthetic approach. 

The enzyme-catalyzed hydrolysis of phthalic units containing polyesters could be used as a potential tool for the block length sequence analysis [134], Thus, copolyesters undergo two kinds of degradation process in the presence of lipase from Chromobacterium viscosum a fast and selective enzymatic hydrolysis of the fumaric ester functions and a slow but non-selective imcat-alyzed hydrolysis of fumaric and phthalic ester functions. 

Whereas acid catalyzed hydrolysis of peptides cleaves amide bonds indiscriminately and eventually breaks all of them enzymatic hydrolysis is much more selective and is the method used to convert a peptide into smaller fragments... 

A number of examples of monoacylated diols produced by enzymatic hydrolysis of prochiral carboxylates are presented in Table 3. PLE-catalyzed conversions of acycHc diesters strongly depend on the stmcture of the substituent and are usually poor for alkyl derivatives. Lipases are much less sensitive to the stmcture of the side chain the yields and selectivity of the hydrolysis of both alkyl (26) and aryl (24) derivatives are similar. The enzyme selectivity depends not only on the stmcture of the alcohol, but also on the nature of the acyl moiety (48). 

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). 

Resolution of Racemic Amines and Amino Acids. Acylases (EC3.5.1.14) are the most commonly used enzymes for the resolution of amino acids. Porcine kidney acylase (PKA) and the fungaly3.spet i//us acylase (AA) are commercially available, inexpensive, and stable. They have broad substrate specificity and hydrolyze a wide spectmm of natural and unnatural A/-acyl amino acids, with exceptionally high enantioselectivity in almost all cases. Moreover, theU enantioselectivity is exceptionally good with most substrates. A general paper on this subject has been pubUshed (106) in which the resolution of over 50 A/-acyl amino acids and analogues is described. Also reported are the stabiUties of the enzymes and the effect of different acyl groups on the rate and selectivity of enzymatic hydrolysis. Some of the substrates that are easily resolved on 10—100 g scale are presented in Figure 4 (106). Lipases are also used for the resolution of A/-acylated amino acids but the rates and optical purities are usually low (107). 

A synthesis of the important biosynthetic intermediate mevalonic acid starts with the enzymatic hydrolysis of the diester A by pig liver esterase. The pro-R group is selectively hydrolyzed. Draw a three-dimensional structure of the product. 

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