Density Functional Theory Calculations in Stereochemical Determination of Terpecurcumins J–W, Cytotoxic Terpene-Conjugated Curcuminoids from Curcuma longa L.

Fourteen
novel terpene-conjugated curcuminoids, terpecurcumins J–W (1–14), have been isolated from the rhizomes
of Curcuma longa L. Among them, terpecurcumins
J–Q and V represent four unprecedented skeletons featuring
an unusual core of hydro­benzannulated­[6,6]-spiroketal (1 and 2), bicyclo[2.2.2]­octene (3–7), bicyclo[3.1.3]­octene (8), and
spiroepoxide (13), respectively. The structures of compounds 1–14 were elucidated by extensive spectroscopic
analysis, and their absolute configurations were established by electronic
circular dichroism, vibrational circular dichroism, and 13C NMR spectroscopic data analysis, together with density functional
theory calculations. The structure and configuration of 1 was further confirmed by single-crystal X-ray diffraction (Cu Kα).
The biogenetic pathways of 1–14 were
proposed, involving Michael addition, condensation, Diels–Alder
cyclo­addition, and electrophilic substitution reactions. Terpecurcumins
showed more potent cytotoxic activities than curcumin and ar-/β-turmerone.
Among them, terpecurcumin Q (8) exhibited IC50 of 3.9 μM against MCF-7 human breast cancer cells, and mitochondria-mediated
apoptosis played an important role in the overall growth inhibition.
Finally, LC/MS/MS quantitative analysis of five representative terpecurcumins
indicated these novel compounds were present in C.
longa at parts per million level.