(+)/(−)-Phaeocaulin A-D four pairs of new enantiomeric germacrane-type sesquiterpenes from Curcuma phaeocaulis as natural nitric oxide inhibitors

摘要

Germacrane-type sesquiterpenes, with a flexible 10-membered ring unit as the structural and conformational features, play a central role in the biosynthesis and synthesis of other sesquiterpenes. In this report, two pairs of new sesquiterpene alkaloids, (+)/(−)-phaeocaulin A [(+)->1/(−)->1] and B [(+)->2/(−)->2], and two pairs of new sesquiterpenes, (+)/(−)-phaeocaulin C [(+)->3/(−)->3] and D [(+)->4/(−)->4], along with one related known analog (>5), were isolated from the rhizomes of Curcuma phaeocaulis. The absolute configurations of (+)->1/(−)->1, (+)->2/(−)->2, (+)->3/(−)->3 and (+)->4/(−)->4 were unambiguously determined by analysis of single-crystal X-ray diffractions and quantum chemical electronic circular dichroism (ECD) method. It is noteworthy that (+)/(−)-phaeocaulin A [(+)->1/(−)->1] and B [(+)->2/(−)->2] are two pairs of rare N-containing germacrane-type sesquiterpenes. A possible biogenetic pathway for >1–5 was postulated. All of the isolated compounds were tested for their inhibitory activity against LPS-induced nitric oxide production in RAW 264.7 macrophages.