Biotransformation structure

Silicon-based Polymeric Materials Mechanistic Organosilicon Chemistry (a) Gas Phase and Photochemical Reactions (b) Hypervalent Silicon, Nucleophilic Substitution, and Biotransformations Structural Organosilicon Chemistry and New Organosilicon Compounds Organic Synthesis using Siiicon. 

B. Testa, G. Cruciani, Structure-metabolism relations and the challenge of predicting biotransformation, in Pharmacokinetic Optimization in Drug Research, B. Testa, H. van de Water-beemd, G. Folkers, R. Guy (Eds.), WHey-VCH, Weinheim, New York, 2001, pp. 65-84. 

The numerous biotransformations catalyzed by cytochrome P450 enzymes include aromatic and aliphatic hydroxylations, epoxidations of olefinic and aromatic structures, oxidations and oxidative dealkylations of heteroatoms and as well as some reductive reactions. Cytochromes P450 of higher animals may be classified into two broad categories depending on whether their substrates are primarily endogenous or xenobiotic substances. Thus, CYP enzymes of families 1-3 catalyze... 

Aqueous solutions are not suitable solvents for esterifications and transesterifications, and these reactions are carried out in organic solvents of low polarity [9-12]. However, enzymes are surrounded by a hydration shell or bound water that is required for the retention of structure and catalytic activity [13]. Polar hydrophilic solvents such as DMF, DMSO, acetone, and alcohols (log P<0, where P is the partition coefficient between octanol and water) are incompatible and lead to rapid denaturation. Common solvents for esterifications and transesterifications include alkanes (hexane/log P=3.5), aromatics (toluene/2.5, benzene/2), haloalkanes (CHCI3/2, CH2CI2/I.4), and ethers (diisopropyl ether/1.9, terf-butylmethyl ether/ 0.94, diethyl ether/0.85). Exceptionally stable enzymes such as Candida antarctica lipase B (CAL-B) have been used in more polar solvents (tetrahydrofuran/0.49, acetonitrile/—0.33). Room-temperature ionic liquids [14—17] and supercritical fluids [18] are also good media for a wide range of biotransformations. 

The complex structure of the enzyme can show a very large substrate-enzyme interaction specificity, which can be traduced to a high degree of chemo-, regio-, or stereoselectivity. For this reason, nowadays, the versatility of biotransformations for synthetic proposals is an excellent tool for organic chemists [9]. 

Technical-grade endosulfan contains at least 94% of two pure isomers, a- and P-endosulfan (Maier-Bode 1968 NRCC 1975). The a- and p-isomers of endosulfan are present in the ratio of 7 3, respectively. Technical-grade endosulfan may also contain up to 2% endosulfan alcohol and 1% endosulfan ether. Endosulfan sulfate is a reaction product found in technical endosulfan it is also found in the environment due to photolysis and in organisms as a result of oxidation by biotransformation (EPA 1979 Coleman and Dolinger 1982). The chemical formula, structure, synonyms, and identification numbers for endosulfan, a-endosulfan, p-endosulfan, and endosulfan sulfate are listed in Tables 3-1, 3-2, 3-3, and 3-4, respectively. 

Borodina Y, Sadym A, Filimonov D, Blinova V, Dmitriev A, Poroikov V. Predicting biotransformation potential from molecular structure. J Chem Inf... 

Attempts have been made to apply the structure-activity concept (Hansch and Leo 1995) to environmental problems, and this has been successfully applied to the rates of hydrolysis of carbamate pesticides (Wolfe et al. 1978), and of esters of chlorinated carboxylic acids (Paris et al. 1984). This has been extended to correlating rates of biotransformation with the structure of the substrates and has been illustrated with a number of single-stage reactions. Clearly, this approach can be refined with the increased understanding of the structure and function of the relevant degradative enzymes. Some examples illustrate the application of this procedure ... 

For a number of reasons, there are some important limitations to the extension of this principle. Biodegradation—as opposed to biotransformation—of complex molecules necessarily involves a number of sequential reactions each of whose rates may be determined by complex regulatory mechanisms. For novel compounds containing structural entities that have not been previously investigated, the level of prediction is necessarily limited by lack of the relevant data. Too Olympian a view of the problem of rates should not, however, be adopted. An overly critical attitude should not be allowed to pervade the discussions—provided that the limitations of the procedures that are used are clearly appreciated and set forth. In view of the great practical importance of quantitative estimates of persistence to microbial attack, any procedure—even if it provides merely orders of magnitude—should not be neglected. 

Biotransformation is applied to situations in which even though degradation is not achieved, minor structural modifications of the test compound have occurred. 

Shih C-C, ME Davey, J Zhou, JM Tiedje, CS Criddle (1996) Effects of phenol feeding pattern on microbial community structure and cometabolism of trichloroethylene. Appl Environ Microbiol 62 2953-2960. Somsamak P, HH Richnow, MM Haggblom (2005) Carbon isotope fractionation during anaerobic biotransformation of methyl ferf-butyl ether and ferf-amyl methyl ether. Environ Sci Technol 39 103-109. Somsamak P, RM Cowan, MM Haggblom (2001) Anaerobic biotransformation of fuel oxygenates under sulfate-reducing conditions. EEMS Microbiol Ecol 37 259-264. 

Very recently Li et al. (2006) reported comparative studies of the similarities and differences between the microbial and mammalian metabolisms of l-THP, the microbial transformation by Penicillium janthinellum, and metabolism in rats [46]. The biotransformation of l-THP by P. janthinellum AS 3.510 resulted in the formation of three metabolites. Their structures (shown in Fig. 5) were identified as L-corydalmine, L-corypalmine, and 9-0-desmethyl-L-THP, by comprehensive NMR and MS analysis [46]. 

Rhodococcus sp. AJ270 was applied to the transformation of a number of racemic cis- and traray-3-aryl-2-methyloxiranecarbonitriles (Figure 8.7). In all cases, the NHase activity proceeded very rapidly and with poor enantioselectivity. In contrast, the amidase activity was strongly dependent upon substrate structure. In general, the biocatalyst displays a strong preference for the unsubstituted phenyl side chain or /wa-substituted phenyl side chain compared with ortho- or meta-, and this is manifest both with respect to observed conversion and rate and also observed enantioselectivity. In contrast, the biotransformations of... 

Whole-cell biotransformation processes have been successfully applied for commercial production of pharmaceuticals, either as the drug substance itself or as an intermediate for the synthesis of the final drug substance. Some examples of the whole-cell biotransformation processes used by pharmaceutical industry are shown in Table 10.1. The structures of the biotransformation products are shown in Figure 10.1. 

Figure 10.1 Structures of biotransformation products from Table 10.1...

One advantage of whole-cell biotransformation that has not been addressed adequately in this chapter is the ability to modify compounds with complex structure, such as natural products. Natural products are ideal substrates for biotransformation reactions since they are synthesized in a series of enzymatic reactions by the whole cells. The modification of natural products by biotransformation has been reviewed recently by Azerad [ 13] and a majority of the modifications were carried out by whole-cell biotransformations. Additional examples of modification of natural products by whole-cell biotransformations can also be found in the review article by Patel [2]. Natural products are an important source of new drugs and new drug leads [53]. The use of biotransformation, especially whole-cell biotransformation, in modification of natural products for lead optimization and generating libraries of derivatives for S AR and screening studies is important for the pharmaceutical industry. 

In addition to this transformation, other structural relationships between metabolites from green algae of the family of Udoteaceae are likely to result from biotransformations of stored precursors. It has been concluded that udoteatrial (52) can arise out of the transformation of udoteal (53) (Scheme 15), and other... 

Both purified laccase as well as the crude enzyme from the WRF Cerrena unicolor were used to convert the dyes in aqueous solution. Biotransformation of the dyes was followed spectrophotometrically and confirmed by high performance liquid chromatography. The results indicate that the decolorization mechanism follows MichaeliseMenten kinetic and that the initial rate of decolorization depends both on the structure of the dye and on the concentration of the dye. Surprisingly, one recalcitrant azo dye (AR 27) was decolorized merely by purified laccase in the absence of any redox mediator [46],... 

Kandelbauer A, Erlacher A, Cavaco-Paulo A, Guebitz GM (2004) Laccase catalyzed decolorization of the synthetic dye Diamond Black PV 200 and some structurally related derivatives. Biocatal Biotransformation 22 331-339... 

The answer is local anesthetic properties it can block the initiation or conduction of a nerve impulse. It is biotransformed by plasma esterases to inactive products. In addition, cocaine blocks the reuptake of norepinephrine. This action produces CNS stimulant effects including euphoria, excitement, and restlessness Peripherally, cocaine produces sympathomimetic effects including tachycardia and vasoconstriction. Death from acute overdose can be from respiratory depression or cardiac failure Cocaine is an ester of benzoic acid and is closely related to the structure of atropine. 

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