Structures of Modified Cardenolides. 1. Lactam Analogues of Isodigitoxigenin

The crystal structures of two synthetic lactam derivatives of digitoxigenin have been determined by x-ray crystallography. The crystal data for the major product: (20S,21R)-3β-hydroxy-14,21-epoxy-5β,14β,20-cardanolactam (4a) hydrate, orthorhombic system, P2₁2₁2₁, a = 1 1.953, b = 23.611, c = 7.502 Å, Z = 4. The crystal data for the minor product: (20R,21S)-3β-hydroxy-14,21-epoxy-5β,14β,20-cardanolactam (4b), monoclinic, P2₁, a = 11.472,6 = 7.7771, c = 11.463 Å, β = 97.71°, Z = 2. These crystal structures establish the stereochemistry of the C(20), C(21) ring junctions as cis-equatorial-axial and cis-axial-equatorial for 4a and 4b, respectively. The structure of 4a also indicates that isodigitoxigenin also has a cis-equatorial-axial configuration. There are no unusually short intramolecular nonbonded contacts involving the lactam rings in either structure, although models had indicated these configurations would require close contacts. The only conformational differences between these two structures and digitoxigenin occur in the region of the lactam ring despite the strain introduced by the formation of a ring to O(14).