158 Essays in Biochemistry 



tions have been made more stringent by Wilcox et al., 6 who pointed 

 out that the Ogston scheme is strictly correct only if a fourth condition 

 such as steric hindrance prevents the approach of the substrate from 

 the opposite side, since an interaction as in TVb would place the group 

 a" at the reactive site a'. 



Since the Ogston scheme provides a very satisfactory explanation 

 for the complete asymmetry of most enzymatic processes, it apparently 

 has been assumed by some investigators that a three-point attachment 

 between the symmetric substrate and the asymmetric agent is essential 

 for any differentiation of identical groups even if the selectivity is only 

 partial. It is very doubtful that Ogston entertained such thoughts, 

 and a clear statement to the contrary was made by Wilcox. 2 A most 

 emphatic denial can be found in a very lucid analysis by Schwartz 

 and Carter, 4 which may be summarized as follows: Although the sub- 

 stituents a in Caabc are identical and although they are located in a 

 symmetrical molecule, their locations within that molecule nevertheless 

 are sterically non-equivalent. If one views from one substituent a the 

 three other substituents of the central carbon atom, the groups a, b, c 

 appear in a clockwise sequence; whereas a counterclockwise order 

 prevails if one views from the other a group. If one orients the mole- 

 cule in a predetermined way (e.g., as in I with groups b and c to the 

 rear and with b above c), invariably the same group a will be directed 

 to the right or to the left, respectively. Since the two a groups can 

 be distinguished by inspection, their location cannot be sterically 

 equivalent. 



A plane through the central carbon atom which bisects substituents 

 b and c cuts the molecule into halves which are related to each other 

 as object to mirror image but which are not superimposable as long 

 as b and c are different. Since this situation resembles in some respects 

 that prevailing in a meso compound which often can be cut into mirror- 

 image halves that are not superimposable, Schwartz and Carter pro- 

 posed the term meso carbon atom for one substituted with two identical 

 and two different substituents (Caabc). It should be noted that the 

 last argument for the steric non-equivalence of the two a groups must 

 be used with caution, since such a molecule as Caaab in which all 

 a groups are sterically equivalent also can be cut into mirror-image 

 halves that cannot be superimposed upon each other. Another failure 

 of this criterion was noted by the authors themselves. 4 



If we consider the approach of a molecule E to one or the other 

 substituent a in Caabc leading to a one-point attachment (either by 

 covalence, electrovalence, hydrogen bonding, or some other force) the 



