Proprochiral centers

Flood, Thomas C., Stereochemistry of Reactions of Transition Metal-Carbon Sigma Bonds, 12, 37. Floss, Heinz G., Stereochemistry of Biological Reactions at Proprochiral Centers, 15, 253. Freedman, T. B., Stereochemical Aspects of Vibrational Optical Activity, 17, 113. 

Stereochemistry of Biological Reactions at Proprochiral Centers (Floss, Tsai, and... 

In a system Xaaaa the a groups are, of course, also homotopic and thus indistinguishable. By the same formalism used above such a center can be called proproprochiral, because it is three substitution steps removed from a chiral center. Hence, three isotopic and/or heteroatomic replacements are required in order to study the steric course of reactions at such a center. The only chiral version of a proproprochiral center synthesized to date is an inorganic phosphate molecule carrying one heteroatomic and two isotopic replacements, (R)- and (S)-[I60,170,180]phosphorothioate. The presence of the sulfur heteroatom, of course, gives this chirally labeled species the properties of a proprochiral center with the concomitant simplification in the analytical methodology required to distinguish an R from an S isomer. 

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... 

A. Biological Reactions Involving a Proprochiral Phosphorus Center.287... 

In the following sections we discuss the methods that have been developed to study the steric course of reactions at proprochiral and proproprochiral centers on carbon and phosphorus, and some of the biochemical applications of these methods. Specifically, we consider chiral methyl groups, chiral malonic acid, chiral phosphate monoesters, and chiral inorganic phosphate. 

The enzyme-catalyzed reactions involving a proprochiral phosphorus center can be categorized into the following types based on the stereochemistry involved ... 

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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