Niemann’s compound

The work of Silver and Sone (104) favors, however, the equatorial orientation of the ester group. Thus, the results of these studies gave rise to very intense controversies regarding the orientation (axial or equatorial) of the carbomethoxy function of d-KCTI, and hence of enzyme-bound l-APME (104,105). Whether the orientation of this ester function is axial or equatorial has not been unambiguously resolved with Niemann s compound and its derivatives. The reason for this probably lies in the fact that in most of the compounds used the structural features of the normal substrates of a-chymotrypsin are so grossly altered as to cast strong doubts on the validity of the models. 

A careful comparison of molecular models leads to the conclusion that Niemann s compound (d-KCTI) and Belleau s compound (S,Seq conformer) are related as a key is to its lock only when the ester function of d-KCTI is axially oriented in the a-chymotrypsin-bound state (Fig. 4.4). Therefore, Belleau s and Niemann s compounds are identical at the molecular level if the ester function is axially oriented in the Niemann s product. The versatility of Belleau s compound makes it a better model for analyzing the conformation of a-chymotrypsin-bound substrates. 

Fig. 4.4. Dreiding stereomodels showing that the D-configuration of Niemann s compound can be superimposed on Belleau s biphenyl model compound.

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