Different intra- and intermolecular hydrogen-bonding patterns in (3S,4aS,8aS)-2-[(2R,3S)-3-(2,5-X2-benzamido)-2-(2,5-X2-benzoyloxy)-4-phenylbutyl]-N-tert-butyldecahydroisoquinoline-3-carboxamides (X = H or Cl): compounds with moderate aspartyl protease inhibition activity

• Main Authors: Wilson Cunico, Maria de Lourdes G. Ferreira, James L. Wardell, William T. A. Harrison
• Format: Article
• Language: English
• Published: International Union of Crystallography 2017-06-01
• Series: Acta Crystallographica Section E: Crystallographic Communications
• Subjects: crystal structure; malaria; isoquinolinecarboxamide; hydrogen bonding; aspartyl protease inhibition activity
• Online Access: http://scripts.iucr.org/cgi-bin/paper?S2056989017007800

The crystal structures of (3S,4aS,8aS)-2-[(2R,3S)-3-benzamido-2-benzoyloxy-4-phenylbutyl]-N-tert-butyldecahydroisoquinoline-3-carboxamide, C38H47N3O4, (I), and (3S,4aS,8aS)-2-[(2R,3S)-3-(2,5-dichlorobenzamido)-2-(2,5-dichlorobenzoyloxy)-4-phenylbutyl]-N-tert-butyldecahydroisoquinoline-3-carboxamide, C38H43Cl4N3O4, (II), are described. Despite their chemical similarity, they adopt different conformations in the solid state: (I) features a bifurcated intramolecular N—H...(N,O) hydrogen bond from the tert-butylamide NH group to the piperidine N atom and the benzoate O atom, whereas (II) has an intramolecular N—H...O link from the benzamide NH group to the tert-butylamide O atom. In the crystal of (I), molecules are linked by C(4) amide N—H...O hydrogen bonds into chains propagating in the [010] direction, with both donor and acceptor parts of the benzamide group. In the extended structure of (II), C(11) N—H...O chains propagating in the [010] direction arise, with the donor being the tert-butylamide NH group and the acceptor being the O atom of the benzamide group.