Crystal and molecular structure of eupatolide, the major cytotoxic principle from Eupatorium formosanum HAY

Abstract

Single-crystal X-ray analysis of eupatolide [8β-hydroxygermacra-1(10),4,11(13)-trien-12,6α-olactone] has established the detailed molecular conformation and the absolute configuration follows from the known sign of the Cotton effect of the n→π* transition of the CC–CO chromophore. Crystals are orthorhombic, space group P212121, with a= 10.04(1), b= 13.82(1), c= 9.68(1)Å, Z= 4. The structure was solved by direct phase-determining methods and refined by full-matrix least-squares calculations to R 0.074 over 957 statistically significant reflections from diffractometer measurements. The trans,trans-cyclodecadiene ring is in a chair,chair-conformation with the C(4) and C(10) methyl groups syn-oriented on the β-face of the molecule. Analysis of deviations from ideal geometry at the trisubstituted double-bond carbon atoms reveals that in both cases the majority of the distortion arises from twist around the double bond.