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

Abstract

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 (20R,24S)-20,24-epoxydammarane-3β,12β,25-triol, C30H52O4, (III), and (20R,24R)-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 R4(4)(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 C4(4)(8) motif.

Crystal structure of (3S,8R,10R,12R,14R)-12-hydroxy-4,4,8,10,14-pentamethyl-17-((R)-2,6,6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate, C32H54O4

“…One of the two molecules is shown in the figure. Bond lengths and angles are very similar to those given in the literature for protopanaxadiol [9][10][11][12][13].…”

Synthesis and Crystal Structure of Ocotillol-Type Metabolites Derived from (20R)-Protopanaxadiol

“…Our previous study has reported the synthesis and crystal structures of two C-24 epimeric (20R)-PPD metabolites (M1 and M2, Scheme 1). 14 In the present study, four ocotillol-type (20R)-PPD metabolites, M3, M4, M9 and M10, are synthesised from M1 and M2, respectively (Scheme 1). Their structures are confirmed by HRMS, 1 H NMR and 13 C NMR.…”

Synthesis and In Vitro Anti-inflammatory Activity of C20 Epimeric Ocotillol-Type Triterpenes and Protopanaxadiol

“…In our previous study, epimers 9 and 10 were synthesized through the direct oxidation of 20(R)-PPD with m-CPBA [28]. However, separation of the two C-24 isomers by silica gel column chromatography was difficult.…”