Structural Differentiation in Asymmetric Reactions 157 



tions, therefore, appears not to be an intrinsic one but rather a reflec- 

 tion of the diagnostic tool employed for demonstrating the asymmetry 

 of the process. It can be shown that the selective reactivity of one 

 of a set of identical substituents is possible in certain compounds, but 

 not in others. It, therefore, becomes a problem of both theoretical 

 and practical interest to determine the structural basis of such differ- 

 entiation. Several criteria 2 ~ 4 have been proposed in answer to this 

 question. However, one of these rules 3 is unreliable, 4 and they all 

 fail in providing information about situations that are likely to be 

 encountered. It is the purpose of this discussion to propose a general 

 criterion and to compare it with those which have been advanced by 

 others. 



The possibility that two identical substituents a in a molecule Caabc 

 can be distinguished from each other in a process catalyzed by an 

 enzyme was postulated by Ogston. 5 The reality of the phenomenon 

 has been amply demonstrated in the case of citric acid and other sub- 

 stances. As is well known, the mechanism envisaged by Ogston as- 

 sumes an attachment of three groups of the substrate to three sites 

 of the enzyme, of which only one is catalytically active. If the sites 

 a' and a" can combine specifically with the groups * a' or a", and the 

 sites /S and y with the groups b and c, respectively, if the reaction 

 proceeds only if three groups are simultaneously engaged, and if only 

 a' but not a" can catalyze the reaction, then an enzyme constituted 

 as TVa or V will cause a reaction at a' but not at a". These stipula- 



* Throughout this discussion atoms or groups of atoms designated by a', a", 

 a'" are defined as being identical and are designated by different symbols merely 

 to facilitate discussion. Furthermore, unless stated otherwise, all substituents a, 

 b, c, etc., are assumed to be symmetric. Bonds drawn in solid triangles are 

 directed towards the observer; those in broken lines towards the rear. 



