Synthesis and crystal structures of C24-epimeric 20( R)-ocotillol-type saponins.

Ocotillol-type saponins have a wide spectrum of biological activities. Previous studies indicated that the configuration at the C24 position may be responsible for their stereoselectivity in pharmacological action and pharmacokinetics. Natural ocotillol-type saponins share a 20( S)-form but it has been found that the 20( R)-stereoisomers have different pharmacological effects. The semisynthesis of 20( R)-ocotillol-type saponins has not been reported and it is therefore worthwhile clarifying their crystal structures. Two C24 epimeric 20( R)-ocotillol-type saponins, namely (20 R,24 S)-20,24-epoxydammarane-3β,12β,25-triol, C30H52O4, (III), and (20 R,24 R)-20,24-epoxydammarane-3β,12β,25-triol monohydrate, C30H52O4·H2O, (IV), were synthesized, and their structures were elucidated by spectral studies and finally confirmed by single-crystal X-ray diffraction. The (Me)C-O-C-C(OH) torsion angle of (III) is 146.41 (14)°, whereas the corresponding torsion angle of (IV) is −146.4 (7)°, indicating a different conformation at the C24 position. The crystal stacking in (III) generates an R44(8) motif, through which the molecules are linked into a one-dimensional double chain. The chains are linked via nonclassical C-H...O hydrogen bonds into a two-dimensional network, and further stacked into a three-dimensional structure. In contrast to (III), epimer (IV) crystallizes as a hydrate, in which the water molecules act as hydrogen-bond donors linking one-dimensional chains into a two-dimensional network through intermolecular O-H...O hydrogen bonds. The hydrogen-bonded chains extend helically along the crystallographic a axis and generate a C44(8) motif. [ABSTRACT FROM AUTHOR]