Two Crystalline Forms of Sesquiterpene Lactone Helenalin - X-Ray and NMR Study

Abstract

Helenalin, a naturally occurring sesquiterpene lactone of the pseudoguaianolide type, has been reported to exist in two polymorphic forms, both crystallizing in the monoclinic space group P21. In this paper we report the X-ray structure of the third room temperature polymorph, crystallizing in the orthorhombic space group P212121. The isolated molecules in all three polymorphs exhibit nearly the same molecular conformation, so the three crystalline modifications differ mainly in the mode the molecules pack in the solid state. Two main hydrogen bond acceptors, the oxygen atom of the cyclopentenone ring and the oxygen atom of the lactone carbonyl group, are competing in the hydrogen bond formation with the secondary hydroxyl group. Having an access to two polymorphs which differ in the hydrogen bond acceptors, we have performed the solid state 13C NMR measurements using a cross-polarization magic angle spinning technique. By comparison of the spectra taken in non-polar solvent with the spectra taken in the solid state we were able to demonstrate the shielding effects resulting from the intermolecular hydrogen bonding in crystals. The fast conformational equilibrium between two conformers TC(10) and TC(7) was suggested from NMR study of helenalin in solution.

The ambrosanolide cumanin inhibits macrophage nitric oxide synthesis: some structural considerations

“…Helenalin was isolated from Helenium mexicanum as previously reported (Petit and Bolzinski, 1974) and its structure was confirmed by comparison with literature data (Rychlewska et al, 1995).…”

Structure−Cytotoxicity Relationships of Some Helenanolide-Type Sesquiterpene Lactones

“…These discrepancies may be caused by different stereochemistry and the resulting differences in the three-dimensional shape. The helenalin molecule has been shown to possess a rather high degree of conformational flexibility and is subject to a very fast conformational exchange at room temperature, , whereas mexicanin I, due to the 7,8-trans fused lactone ring, is a rather rigid molecule. This difference may affect the bioactivities.…”

“…9 Sesquiterpene Lactones-Semisynthetic Derivatives. Mexicanin I Acetate (7). Ten mg (38.2 µmol) of mexicanin I was refluxed for 3 h with 5 mL of a 10% solution of Ac 2 O in pyridine.…”

Cytotoxic Activity of Extracts from Plants of Central Argentina on Sensitive and Multidrug‐Resistant Leukemia Cells: Isolation of an Active Principle from Gaillardia megapotamica

“…Only 1 exerted a toxic effect at this concentration. According to 1 H and 13 C NMR spectra (copies of the original spectra are obtainable from the corresponding author), the compound was identified as the sesquiterpene lactone helenalin C 15 H 18 O 4 ( 1 ; m / z 262) [ 41 ] (yield 0.79 g/100 g of dried and crushed plant material, by HPLC) ( Figure 1 ).…”