Natural nitric oxide (NO) inhibitors from the rhizomes of Curcuma phaeocaulis.

An exploration we carried out for isolating nitric oxide (NO) inhibitors from the rhizomes of Curcuma phaeocaulis afforded one new salvialane-type sesquiterpene, phasalvione (1), two novel nor-sesquiterpenes, phaeocaudione (2) and phaeocauone (3), one aromatic acid 3-methyl-4-(3-oxo-butyl)-benzoic acid (4), two γ-elemene-type sesquiterpenes, 8ß(H)-elema-1,3,7(11)-trien-8,12-lactam (5) and 8ß-methoxy-isogermafurenolide (6), one eudesmane-type sesquiterpene, phaeusmane I (7), and one cyclic diarylheptanoid, phaeoheptanoxide (8). Their structures were established based on extensive spectroscopic analysis. The absolute configurations of compounds 1 and 2 were assigned using the circular dichroism data of the [Rh2(OCOCF3)4] complex, and the absolute configuration of 1 was further established by single crystal X-ray crystallography. It is noteworthy that compounds 5­7 were racemates analyzed by chiral HPLC. Furthermore, the inhibitory effects of the isolated compounds on nitric oxide production in LPS-activated macrophages were evaluated. Compounds 1, 3 and 4 showed strong inhibitory activities on NO production with IC50 values of 7.46 ± 0.69, 2.35 ± 0.17 and 3.49 ± 0.31 µM, respectively. A plausible biosynthetic pathway for 1­4 in C. phaeocaulis was also discussed.

Biotransformation of Curcumenol by Mucor polymorphosporus.

Biocatalysis of curcumenol (1) was performed by Mucor polymorphosporus AS 3.3443. Six metabolites including five new compounds were obtained, and their structures were elucidated as 10ß-hydroxy-9,10-dihydrocurcumenol (2), 2ß-hydroxycurcumenol (3), 15-hydroxycurcumenol (4), 12-hydroxycurcumenol (5), 1-hydroxy-4αH-guai-1,6,9-triene-2,8-dione (6), and 5-hydroxycarbonyl-1-oxo-3,7-dimethylindane (7) by spectroscopic analysis. M. polymorphosporus catalyzed unusual degradation and rearrangement reactions to generate a ring-contracted metabolite (7) of curcumenol (1). Curcumenol (1) and metabolites 4-7 exhibited inhibitory activities against lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages, with 7 exhibiting more potent activity than curcumenol.

Four new sesquiterpenes from the rhizomes of Curcuma phaeocaulis and their iNOS inhibitory activities.

Three new guaiane-type sesquiterpenes named phaeocaulisins K-M (1-3), and one germacrane-type sesquiterpenoid with new ring system of 1,5- and 1,8-ether groups named phagermadiol (4), were isolated from rhizomes of Curcuma phaeocaulis. Their structures were established based on extensive spectroscopic analysis. Compound 1, the first example of norsesquiterpene with tropone backbone, and compound 3 with a novel 1,2-dioxolane sesquiterpene alcohol were isolated from the genus Curcuma. All of the isolated compounds were tested for inhibitory activity against lipopolysaccharide-induced nitric oxide (NO) production in RAW 264.7 macrophages. Compound 3 inhibited NO production with IC50 value of 6.05 ± 0.43 µM. The plausible biosynthetic pathway for compounds 3 and 4 in C. phaeocaulis was also discussed.

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

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.

A New Triterpenoid from the Aerial Parts of Agrimonia pilosa.

(1S,3R,17R,18R,19R,20R,22R)-1,3,19,22-tetrahydroxy-28-norurs-12-en-2-one (1), along with 5 known triterpenoids (2-6), were isolated from the aerial parts of Agrimonia pilosa Ledeb. Their structures were established based on extensive spectroscopic and MS analysis. The absolute configuration of compound 1 was deduced by circular dichroism (CD). Compound 1 was the first example of a 28-norursene backbone isolated from the genus Agrimonia. Compounds 2-6 were tested for anti-inflammatory activities against RAW 264.7 macrophages. A plausible biosynthetic pathway for compound 1 in A. pilosa was also proposed.