Stereochemical Study of a Bradicardisant Benzazepine-Type Drug. X-Ray Structure of the Chloride Salt and High-Field NMR Study of the Stereochemistry in Solution
✍ Scribed by Delphine Duval; Philippe Hennig; Jean Paul Bouchet; Joel Vian; Jean Louis Peglion; Jean Paul Volland; Nicole Platzer; Jean Guilhem
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 387 KB
- Volume
- 35
- Category
- Article
- ISSN
- 0749-1581
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✦ Synopsis
A chiral bradicardisant benzazepine-type drug with an asymmetric carbon and a tertiary amino nitrogen was studied as the chloride salt. X-ray analysis in the solid state of the salt formed upon protonation of the base shows the occurrence in the unit cell of two diastereomeric species with horseshoe-shaped structures. NMR parameters were obtained for the base and for the protonated species in solution. A conformational study by 2D NOESY and ROESY NMR techniques led to the conclusion that conformations similar to the solid-state structures were retained in solution. Over a wide range of pH, in particular in alkaline solution or under biological conditions, a conformation similar to that of the 1º(R) N(R) diastereomer is observed. The diastereomeric species 1º(R) N(R) and 1º(R) N(S) were clearly identiÐed at low pH values with conformations similar to their solid-state structures.