A CRYSTAL-STATE, SOLUTION AND THEORETICAL-STUDY OF THE PREFERRED CONFORMATION OF LINEAR C-ALPHA,C-ALPHA-DIPHENYLGLYCINE DERIVATIVES AND DIPEPTIDES WITH POTENTIAL ANTICONVULSANT ACTIVITY

Several linear molecules containing the C-alpha,C-alpha-diphenylglycine residue were prepared as potential anticonvulsants. The conformational preferences of the C-alpha,C-alpha-diphenylglycine residue were assessed in these synthetic derivatives and dipeptides by X-ray diffraction, FTIR absorption and H-1 NMR techniques, and by conformational energy computations. Five (out of six) derivatives adopt the fully extended C-5 conformation in the crystal state. This intramolecularly H-bonded form is largely populated in chloroform solution in all the derivatives investigated. Conformational energy computations in vacuo support the view that the intramolecularly H-bonded C-7-ring form is the most stable structure for these compounds. Only one linear derivative exhibits a (modest) anticonvulsant activity. (C) Munksgaard 1994.