Enzymatic stereochemistry

From H. Hirschmann, Newer Aqseeis of Enzymatic Stereochemistry in Comprehensive Biochemistry. Vol 12, M. Florkin and E. H. Stotz, sis. By permission of Elsevier Publishing Go.]... 

Hirschmann, H. Newer Aspects of Enzymatic Stereochemistry, in Comprehensive Biochemistry, Vol. 12, pp. 236ff. (Florkin, M., Stotz, G. H. eds). New York American Elsevier Publishing Co. 1964... 

The wM-diacetate 363 can be transformed into either enantiomer of the 4-substituted 2-cyclohexen-l-ol 364 via the enzymatic hydrolysis. By changing the relative reactivity of the allylic leaving groups (acetate and the more reactive carbonate), either enantiomer of 4-substituted cyclohexenyl acetate is accessible by choice. Then the enantioselective synthesis of (7 )- and (S)-5-substituted 1,3-cyclohexadienes 365 and 367 can be achieved. The Pd(II)-cat-alyzed acetoxylactonization of the diene acids affords the lactones 366 and 368 of different stereochemistry[310]. The tropane alkaloid skeletons 370 and 371 have been constructed based on this chemoselective Pd-catalyzed reactions of 6-benzyloxy-l,3-cycloheptadiene (369)[311]. 

In this chapter we consider amino acid production by fermentation and by chemo-enzymatic methods. We first consider the stereochemistry of amino adds and the importance of chirality in chemical synthesis. General approaches to amino add fermentation and recovery of amino adds from fermentation broths are then dealt with, followed by a detailed consideration of the production of L-phenylalanine by direct fermentation. Later in this chapter, chemo-enzymatic methods of amino acid... 

Stereoinversion Stereoinversion can be achieved either using a chemoenzymatic approach or a purely biocatalytic method. As an example of the former case, deracemization of secondary alcohols via enzymatic hydrolysis of their acetates may be mentioned. Thus, after the first step, kinetic resolution of a racemate, the enantiomeric alcohol resulting from hydrolysis of the fast reacting enantiomer of the substrate is chemically transformed into an activated ester, for example, by mesylation. The mixture of both esters is then subjected to basic hydrolysis. Each hydrolysis proceeds with different stereochemistry - the acetate is hydrolyzed with retention of configuration due to the attack of the hydroxy anion on the carbonyl carbon, and the mesylate - with inversion as a result of the attack of the hydroxy anion on the stereogenic carbon atom. As a result, a single enantiomer of the secondary alcohol is obtained (Scheme 5.12) [8, 50a]. 

Gold and Linder (17) studied the esterase catalyzed hydrolysis of A-(-)-acetoxymethyl-(l-phenylethyl)nitrosamine. They found that the stereochemistry of 1-phenylethanol produced in the reaction was the same as that observed in the base catalyzed hydrolysis of the nitrosamine and also of N-(l-phenylethyl)nitrosocarbamate. These results indicated that the same diazotate was produced in all three reactions. The fact that no irreversible inhibition of the enzymatic hydrolysis of the nitrosamine was observed, while extensive irreversible inhibition was obtained with the nitrosocarba-mate, led these workers to conclude that the a-hydroxynitro-samine produced by the hydrolysis had sufficient stability to diffuse away from the active site of the enzyme. 

It should be noted that as early as 1993, Kurth and coworkers investigated the enzymatic transformation of bis-epoxides of type 8-51 using cytosolic epoxide hydrolase from rat liver. However, at that time the regio- and stereochemistry of the obtained THFs had not been investigated. 

It was shown that microsomal epoxide hydrolase-catalyzed trans-addition of water to BaP 9,10-epoxide occurs stereospecifically at the C-9 position (15). Since BaP is metabolized essentially to an optically pure 9R,10R-dihydrodiol (13 and L5 Table I), the 9,10-epoxide formed in BaP metabolism must have 9S,10R absolute stereochemistry (Figure 1). Similarly, the 7,8-epoxide formed in BaP metabolism is hydrated specifically at the C-8 position to form the 7R,8R-dihydrodiol (14.21). Hence the enzymatically formed 7,8-epoxide intermediate has 7R,8S absolute stereochemistry (Figure 1). Although the 7R,8R-dihydrodiol is formed almost exclusively from BaP metabolism in rat liver microsomes (Table I) and in bovine bronchial explants (25). the 7S,8S-dihydrodiol is also formed from BaP metabolism in mouse skin epidermis in vivo (5). 

As we have seen a stereoselective reaction is one in which there is a preponderance of one isomer irrespective of the stereochemistry of the reactant. The enzymatic reduction of pyruvic acid is stereoselective when the chiral molecules of the enzyme complexes with achiral pyruvic acid, they given a preponderance of one form of pyruvic acid-enzyme complex which then gives a single form of lactic acid. 

Levy, H. R., Talalay, P., Vennesland, B. The steric course of enzymatic reactions at meso carbon atoms application of hydrogen isotopes. In progress in stereochemistry (ed. de la Mare and Klyne), Vol. 3, p. 299—349. (London Butterworths 1962. 

Fig. 10.28. The stereochemistry of enzymatic hydrolysis of stilbene oxide. The achiral (meso) r/.v-sli Ibene oxide (10.7) yields only one of the two enantiomers of IhreoA,2-diphcnylethane-1,2-diol (10.122). In contrast, the chiral trans-stilbene oxide (10.121) is hydrated exclusively to meso-l -diphenylethane-l -diol [182][183]. 

Fig. 10.29. Stereochemistry of the EH-catalyzed hydration of 1,2-epoxycyclohexane (10.5) to the chiral tiansfR,R)-cyclohexane-l,2-diol (10.124). The substrate in the catalytic site adopts the conformation shown (3,4M helicity), and enzymatic attack occurs at the (,S )-con figured C-atom with /ra .v-diaxial opening [185][186]. 

Enzymatic Reactions, Stereochemistry of, by Use of Hydrogen Isotopes (Arigoni and Eliel) 4 127... 

It is worth noting that in this synthesis of Cecropia juvenile hormone a strategy which is the reverse of the one developed by W.S. Johnson [8] for the synthesis of steroids and other fused polycyclic systems bearing cyclohexane rings is used. This method involves a non-enzymatic cyclisation of a polyunsaturated intermediate with the appropriate stereochemistry (all-trans) (Scheme 13.3.6). Such cyclisation occurs with a really amazing stereoselectivity and several new chiral centres with the correct stereochemistry are created in one single step ... 

Katayama T, Masaoka T, Yamada H (1997) Biosynthesis and stereochemistry of lig-nans in Zanthoxylum ailanthoides 1. (-l-)-Lariciresinol formation by enzymatic reduction of ( )-pinoresinols. Mokuzai Gakkaishi 43 580-588... 

Synthesis of (-)-O-methylcryptaustoline iodide (14) from (S)-(-)-laudanoso-line by chemical and later by enzymatic means (vide infra) established the (5) configuration at C-12a in cryptaustoline (7). The stereochemistry of the N-methyl group in 1 has not been determined. 

Currently, only a handful of examples of unique protein carboxylate-zinc interactions are available in the Brookhaven Protein Data Bank. Each of these entries, however, displays syn coordination stereochemistry, and two are bidentate (Christianson and Alexander, 1989) (Fig. 5). Other protein structures have been reported with iyw-oriented car-boxylate-zinc interactions, but full coordinate sets are not yet available [e.g., DNA polymerase (Ollis etal., 1985) and alkaline phosphatase (Kim and Wyckoff, 1989)]. A survey of all protein-metal ion interactions reveals that jyw-carboxylate—metal ion stereochemistry is preferred (Chakrabarti, 1990a). It is been suggested that potent zinc enzyme inhibition arises from syn-oriented interactions between inhibitor carboxylates and active-site zinc ions (Christianson and Lipscomb, 1988a see also Monzingo and Matthews, 1984), and the structures of such interactions may sample the reaction coordinate for enzymatic catalysis in certain systems (Christianson and Lipscomb, 1987). 

Guy Lemiere was born in Antwerp, Belgium, and studied chemistry at the Universities of Antwerp and Ghent. In 1975 he obtained a PhD in organic chemistry from the University of Antwerp on the subject Study on enzymatic in vivo and in vitro reductions of cyclic ketones . He built up all his academic career at the University of Antwerp. His scientific interests evolved from the stereochemistry of enzymatic reactions to natural products and further to heterocyclic chemistry, especially the chemistry of pyridazines. In 2004 he organized together with Bert Maes the 9th International Symposium on the Chemistry and Pharmacology of Pyridazines in Antwerp. He is an author of around 80 scientific papers. 

In principle, bifunctional aldehydes should be able to engage in twofold enzymatic aldol additions to both of their acceptor carbonyls in a fashion to be classified as a tandem reaction, that is, without the need for isolation of intermediates. Depending on the specificity of the enzyme used and on the functionalization in the starting material, the isomeric constitution as well as the absolute and relative stereochemistry should be deliberately addressable. Therefore, we engaged in a program to evaluate the scope and the Hmitations of such two-directional chain elongation processes for the construction of extended poly functional molecules [36]. 

Keywords Chiral fluorinated materials, microbial transformation, enzymatic optical resolution, microorganisms, stereochemistry. 

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