Stereochemistry prochiral centers

Elucidating the stereochemistry of reaction at prochirality centers is a powerful method for studying detailed mechanisms in biochemical reactions. As just one example, the conversion of citrate to (ds)-aconitate in the citric acid cycle has been shown to occur with loss of a pro-R hydrogen, implying that the reaction takes place by an anti elimination mechanism. That is, the OH and H groups leave from opposite sides of the molecule. 

It was not until 1948 that Ogston popularized the concept that by binding with substrates at three points, enzymes were capable of asymmetric attack upon symmetric substrates.d In other words, an enzyme could synthesize citrate with the carbon atoms from acetyl-CoA occupying one of the two -CH2COOH groups surrounding the prochiral center. Later, the complete stereochemistry of the... 

In this Section we shall use the ideas of prochirality in assignment of stereochemical configuration S8) (usually relative — especially meso vs. dl — rather than absolute configuration) and we shall also discuss assignment of prochirality symbol (i.e. recognition of which group is pro-R and which pro-S at a prochiral center). (Recognition of prochiral faces as Re or Si is usually obvious from the stereochemistry of the addition products thereto and will not be discussed here examples are found in Section 5.2). 

The fourth and final chapter, by Heinz G. Floss, Ming-Daw Tsai, and Ronald W. Woodard leads into the realm of biochemistry, dealing with the stereochemistry of biological reactions at proprochiral centers. Prochiral centers are centers... 

The importance of stereochemistry in understanding the mechanism of biological processes has long been appreciated and, since Ogston s classic paper in 1948 (1), stereochemical studies have been extended to prochiral molecules normally thought of as symmetrical. Prochirality has been extensively reviewed, and the literature includes chapters in this series and elsewhere (2-4) and two books (5,6). Extension of the concept to reactions at pro-prochiral centers has also been reviewed in this series (7). 

In this review, we shall concentrate on the stereochemistry of enzymic reactions of amino acids, many of which involve transformations at prochiral centers. We shall use the nomenclature of Hanson (8) to specify the stereochemistry of prochiral atoms and groups as pro-R (Hjj) and pro-S (Hj) and of prochiral faces as Re and Si and the nomenclature of Mislow and Raban (2) to describe prochiral groups as having enantiotopic or diastereotopic relationships. Reviews on the stereochemistry of enzymic reactions of amino acids were published in 1978 (9,10), and since the seminal review by Dunathan in 1971 (11), several reviews comparing the stereochemistry of pyridoxal phosphate-catalyzed enzymic reactions have appeared (12-15). 

Naturally occurring MVA (Fig. 5) is the 3/ isomer (Eberle and Arigoni, 1960) and mevalonate kinase acts only upon this isomer (Lynen and Grassl, 1958 Comforth et al., 1962). In addition, there are three prochiral centers at C-2, C-4, and C-5, and MVA has been synthesized with the methylene groups at these positions stereospecifically labeled with deuterium or tritium (Comforth et al., 1966a,b Donninger and Popjak, 1%6 Blattmann and Retey, 1971 Comforth and Ross, 1970 Scott et al., 1970). This has made it possible to determine the stereochemistry of many reactions in terpenoid biosynthesis (Britton, 1976a). 

Determining the stereochemistry of reactions at prochirality centers is a powerful method for studying detailed mechanisms in biochemical reactions. 

The corresponding esters are much less informative because the centers of chirality in their acyl radicals are structurally protected from racemization like that experienced by translational or rotational motions of prochiral alkyl radicals. In addition, the decarbonylated radicals derived from them are formed long after their acyl precursors have moved to orientations with respect to their aryloxy partners that result in a loss of the memory of their host stereochemistry within a cage see above. Thus, of the Claisen-like photoproducts from irradiation of (7 )-lb, only the BzON (i.e., 3b) retains a measurable amount of optical activity even in the solid phases of long -aIkane. However, in polyethylene hlms, all of the Claisen products from irradiation of (7 )-lb—2-BN, 4-BN, and 3b—exhibit signihcant ee values. In the same media, the photo-Fries products from lb retain virtually all of the enantiomeric purity of the... 

The reactions described in this chapter demonstrate the diversity of reactions and products that are formed from reaction of a Grignard reagent with a prochiral or stereogenic center. Prediction of stereochemistry of the products is complicated by the dependence of the reaction parameters, such as nature of the Grignard reagent and substrate temperature, solvent and conditions and the effect of catalysts. 

A sensitive probe applied to understand the nature of the reaction mechanism of group transfer is the stereochemistry of the overall reaction. The reaction at a phosphoryl center normally is a degenerate question, since a monosubstituted phosphate ester or anhydride is proprochiral at the phosphate center. Phosphate centers at a diester or disubstituted anhydride are prochiral. Two related methods to analyze the stereochemistry at a phosphate center have been developed by the generation of chirality at the phosphorus center. The first approach was developed by Usher et al. (24) and gave rise to the formation of isotopi-cally chiral [ 0, 0]thiophosphate esters and anhydrides (I). Isotopically chiral [ 0, 0, 0]phosphates (II) have also been synthesized and the absolute configurations determined. Two primary problems must first be addressed with respect to both of the methods that have been developed the synthesis of the isotopically pure chiral thiophosphates and phosphates and the analysis of the isotopic chirality of the products. An example of the chiral starting substrates, as developed for ATP, is schematically demonstrated. Ad = adenosine. 

In many cases, substituents not bound to a stereogenic center can strongly influence the stereochemistry of a radical process. Two different types of effect will be discussed here the presence of a prochiral substituent at the radical center of enolate radicals and the presence of an amide moiety next to the radical center. 

Since the insertion of alkenes into M-C bonds proceeds via a four-center transition state, some requirements have to be accomplished namely (1) the alkene and the hydrocarbyl group have to take cis coordination sites (2) the double bond and the M-C bond have to become coplanar and (3) the 1,2-addition is cis, and this controls the relative stereochemistry at both carbons in case of prochiral alkenes (Scheme 6.33). The regio and stereoselectivity of this process controls the tacticity of polymers. 

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