Novel pseudopolymorph of the active metabolite of perindopril

The dimethyl sulfoxide hemisolvate of perindoprilat [sys­tem­atic name: (1S)-2-((S)-{1-[(2S,3aS,7aS)-2-carb­oxy­octahydro-1H-indol-1-yl]-1-oxopropan-2-yl}aza­nium­yl)pentanoate di­methyl sulfoxide hemisolvate], C₁₇H₂₈N₂O₅·0.5C₂H₆OS, an active metabolite of perindopril, has been synthesized, structurally characterized by single-crystal X-ray diffraction and compared with its ethanol disolvate analogue [Pascard et al. (1991). J. Med. Chem. 34, 663–669]. Both compounds crystallize in the ortho­rhom­bic P2₁2₁2₁ space group in the same zwitterionic form, with a protonated alanine N atom and an anionic carboxylate group at the n-alkyl chain. The three structural units present in the unit cell (two zwitterions and the solvent mol­ecule) are held together by a rich system of O—H...O, N—H...O and C—H...O hydrogen-bond con­tacts.

Perindoprilat monohydrate

The title compound [systematic name: (1S)-2-((S)-{1-[(2S,3aS,7aS)-2-carb­oxy­octa­hydro-1H-indol-1-yl]-1-oxo­propan-2-­yl}aza­nium­yl)pentan­oate monohydrate], C₁₇H₂₈N₂O₅·H₂O, (I)·H₂O, the active metabolite of the anti­hypertensive and cardiovascular drug perindopril, was obtained during polymorphism screening of perindoprilat. It crystallizes in the chiral ortho­rhom­bic space group P2₁2₁2₁, the same as the previously reported ethanol disolvate [Pascard, Guilhem, Vincent, Remond, Portevin & Laubie (1991). J. Med. Chem. 34, 663–669] and dimethyl sulfoxide hemisolvate [Bojarska, Maniukiewicz, Sieroń, Fruziński, Kopczacki, Walczyński & Remko (2012). Acta Cryst. C68, o341–o343]. The asymmetric unit of (I)·H₂O contains one independent perindoprilat zwitterion and one water mol­ecule. These inter­act via strong hydrogen bonds to give a cyclic R²₂(7) synthon, which provides a rigid mol­ecular conformation. The geometric parameters of all three forms are similar. The conformations of the perhydro­indole group are almost identical, but the n-alkyl chain has conformational freedom. A three-dimensional hydrogen-bonding network of O—H...O and N—H...O inter­actions is observed in the crystal structure of (I)·H₂O, similar to the other two solvates, but because of the presence of different solvents the three crystal structures have diverse packing motifs. All three solvatomorphs are additionally stabilized by nonclassical weak C—H...O contacts.