Biotransformation reactions hydrolytic

The use of ILs as solvents for biotransformation reactions is, of course, not limited to kinetic resolutions and the use of hydrolytic enzymes. Numerous other... 

In industrial biotransformations, hydrolytic reactions occupy a prominent position for the production of optically active amines, alcohols, and carboxylic acids. Compared with other reactions, hydrolytic reactions are feasible to scale up because they are cofactor-free, relatively simple, and chemically tunable systems. In addition to home-made whole-cell biocatalysts, which are considered to be more cost-effective for specific syntheses, some commercially available hydrolases, including lipases/esterases, epoxide hydrolases, nitrilases, and glycosidases, are also employed for the enantioselective production of chiral chemicals. 

Hydrolysis of epoxides, esters, amides, and related structures is an important biotransformation reaction that limits the therapeutic activity of many drugs and generates therapeutically active drugs from prodmg structures. In a few cases, hydrolytic reactions can generate a toxic structure. Epoxide hydrolases and esterases are members of the a/(3 hydrolase-fold family of enzymes (Morisseau and Hammock, 2005 Satoh and Hosokawa, 2006). Although their substrate specificities are radically different (e.g., lipids, peptides, epoxides, esters, amides, haloalkanes), their catalytic mechanisms are similar. All of these enzymes have an active site catalytic triad composed of a nucleophilic serine or cysteine residue (esterases/amidases), or aspartate residue (epoxide hydrolases) to activate the substrate, and histidine residue and glutamate or aspartate residues that act cooperatively in an acid—base reaction to activate a water molecule for the hydrolytic step. 

The application of lipases in synthetic biotransformations encompasses a wide range of solvolytic reactions of the carboxyl group, such as esterification, transesterification (alcoholysis), perhydrolysis, and aminolysis (amide synthesis) [103]. Transesterification and amide synthesis are preferably performed in an anhydrous medium, often in the presence of activated zeolite, to suppress unwanted hydrolytic side reactions. CaLB (which readily tolerates such conditions [104,105]), PsL, and PcL are often used as the biocatalyst [106]. 

In contrast to the oxidative reactions discussed above, the only reported biotransformations of reserpine (21) and rescinnamine (23) (42-44) appear to involve hydrolytic processes. Reserpine is readily metabolized by liver homogenates from the mouse (43), rat, guinea pig, dog, and cat (44) to yield methyl reserpate (22) and 3,4,5-trimethoxybenzoic acid in yields of up to 70% (43). The use of reserpine labeled with tritium in the 2 and 6 positions of the trimethoxybenzoate residue indicated that no significant metabolism of reserpine by another route occurred before hydrolysis, reserpine and 3,4,5-trimethoxybenzoic acid being the only detectable radioactive components of the incubation mixture at the conclusion of the reaction (44). An... 

By analogy to the biotransformation of rac-221, the structurally related acetyldisilane rac-229 and the acetylsilane rac-231 were also reduced enantioselectively using resting free cells of Trigonopsis variabilis (DSM 70714)282,287. The conversion of rac-229 leads to a mixture of the optically active disilanes (R,R)-230 and (S,R)-230 (yield 75%, enantiomeric purity of both diastereomers >98% ee) and the transformation of rac-231 leads to a mixture of the optically active silanes (R,R)-232 and (S,R)-232 (yield 72%, enantiomeric purity of both diastereomers 94% ee). These reactions were carried out at 37 (rac-229) and 44 °C (rac-231), respectively the substrate concentrations used were 0.53 g/1. Especially remarkable is the biotransformation of the disilane rac-229 which could be realized without a noticeable degree of hydrolytic cleavage of the Si-Si bond. 

Ester and amide hydrolytic reactions are mediated principally by carboxylesterases (GES), though other esterases play a role in the hydrolysis of a limited number of esters. Other key biotransformations include oxidations and conjugation reactions. 

PROBABLE FATE photolysis no direct photolysis, indirect photolysis too slow to be environmentally important, photooxidation half-life in water 2.4-12.2 yrs, photooxidation half-life in air 7.4 hrs-2.5 days oxidation not important, reaction with photochemically produced hydroxyl radicals gives a half-life of 18 hrs hydrolysis hydrolysis (only in surface waters) believed to be too slow to be important, first-order hydrolytic half-life 10 yrs volatilization not expected to be an important transport process sorption sorption onto particulates and com-plexation with organics are dominant transport processes biological processes bioaccumulated in many organisms, biodegraded rapidly in natural soil, some biotransformation, all biological processes are important fates... 

However, not all of these reactions are used in practice. Statistics on the biotransformations reported in publications and patents in the years from 1974 up to 1991 have been compiled (1). It illustrates the predominant application during that period of oxidations (34 %), hydrolytic reactions (22 %), and reductions (17 %). The great number of hydrolytic reactions and condensations can be explained by the simple use of commercially available cell-free enzymes. The use of cell-free preparations have a number of advantages as listed below ... 

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