Stereochemistry prochiral groups

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). 

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. 

More than a decade of experience on Sharpless asymmetric epoxidation has confirmed that the method allows a great structural diversity in allylic alcohols and no exceptions to the face-selectivity rules shown in Fig. 10.1 have been reported to date. The scheme can be used with absolute confidence to predict and assign absolute configurations to the epoxides obtained from prochiral allylic alcohols. However, when allylic alcohols have chiral substituents at C(l), C(2) and/or C(3), the assignment of stereochemistry to the newly introduced epoxide group must be done with considerably more care. 

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... 

Organic chemists have not had much use for prochirality, but it is an important concept for biochemists following the stereochemistry of bio-organic reactions. Almost all biochemical reactions are under the control of enzymes, which function asymmetrically even on symmetrical (but prochiral) molecules. Thus it has been found that only one of the two methylene groups of... 

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). 

At the very start of Chapter 17, we introduced stereochemistry by thinking about the reactions of two sorts of carbonyl compounds. They are shown again here the first has a prochiral carbonyl group. The second, on the other hand, is not prochiral because no stereo genic centre is created when the compound reacts. 

The effect of the ligands is to sterically control the stereochemistry of monomer coordination prior to insertion, as indicated in Fig. 22-11. For C2-symmetric complexes the coordination pocket may be represented by two hindered and two open quadrants (c/. scheme 22-XI). A prochiral monomer such as propene will adopt the orientation where repulsive interactions between the propene-methyl group, the ligand framework, and the growing polymer chain are minimized. With rac-bis(indenyl)metallocene complexes this mechanism necessarily results in an isotactic polymer. 

If there is more than one chiral centre in a molecule, then the maximum number of possible d,l pairs of stereoisomers increases, and is given by the formula 2 1, where n is the number of chiral centres. So, if there are two chiral centres there are four possible stereoisomers, comprising two d,l pairs. Stereoisomers are called diastereomers if their relationship to one another is not enantiomeric. Where two diastereomers differ only in the stereochemistry at one chiral centre, then they are called epimers. If the two c groups in the prochiral example given above were in such positions that if they were replaced diastereomers would be formed, then the c groups would be called diastereotopic. 

Prochirality, Enantiotopic and Diastereotopic Groups and Faces Use of NMR Spectroscopy in Stereochemistry... 

Of particular concern with a-hydroxy carbonyl compounds is the stereochemistry of the hydroxy group attached to the stereogenic carbon because biological activity is often critically dependent on its orientation. A-Sulfonyloxaziridines have played a prominent role in the stereoselective synthesis of this key structural element (Scheme 25). Enantiomerically and diastereomerically enriched materials have been prepared by (1) the hydroxylation of chiral nonracemic enolates with racemic A-sulfonyloxaziridines, for example (63a) (2) the asymmetric hydroxylation of prochiral enolates with enantiopure A-sulfonyloxaziridines and (3) a combination of the first two, double stereodifferentiation. 

We are concerned with the absolute stereochemistry of the product does epoxidation give 5a or 5b Does the Diels-Alder reaction give 7a or 7b There is also a small group of prochiral tetrahedral carbon atoms with enantiotopic functional groups such as the diester 8 or the diene 9. We shall meet examples of all these (and more ) in this chapter. 

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. 

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