Cytotoxic sesquiterpenes from Ligularia platyglossa.

Four sesquiterpene lactones including an eremophilenolide dimer, named as biligulaplenolide, 1, 8beta-hydroxy-1-oxo-(14alpha,15alpha eremophil-7(11),9(10)-dien-12,8alpha-olide, 2, 1-hydroxy-2-oxo-(14alpha,15alpha eremophil-1(10),7(11),8(9)-trien-12,8-olide, 3, 4alpha,8beta,9alpha-trihydroxy- 5alphaEta-7(11)-eudesmen-12,8alpha-olide, 4, along with two known ones, 10alpha-hydroxy-1-oxo-eremophil-7(11),8(9)-dien-12,8-olide, 5, and furanoeremophil-1(10)-ene-2,9-dione, 6, were isolated from the underground organs of Ligularia platyglossa (Franch.) Hand.-Mazz. Their structures were elucidated by spectroscopic methods including single-crystal X-ray diffraction analysis (2 and 3). Their in vitro cytotoxicities against seven cancer cell lines (BGC-823, A549, HL-60, B16, SMMC-7721, BEL7402, Hela) were evaluated. Compounds 2, 3, 5 showed cytotoxic activities on HL-60 cancer cells with IC50 in the range of 24.0 to 51.1 microM, whereas compound 3 exhibited only weak cytotoxic activity against the B16, BEL7402 and Hela cancer cells. Flow cytometric analysis indicated that compound 3 induces Hela cells to apoptotic death after 48 h treatment with 0.38 mM of this compound.

Achiral, selective CCK2 receptor antagonists based on a 1,3,5-benzotriazepine-2,4-dione template.

Novel, achiral 1H-1,3,5-benzotriazepine-2,4(3H,5H)-diones have been prepared and structurally characterized. These compounds are potent CCK(2) receptor antagonists that display a high degree of selectivity over CCK(1) receptors.

Novel, achiral 1,3,4-benzotriazepine analogues of 1,4-benzodiazepine-based CCK(2) antagonists that display high selectivity over CCK(1) receptors.

A series of 1,3,4-benzotriazepine-based CCK(2) antagonists have been devised by consideration of the structural features that govern CCK receptor affinity and the receptor subtype selectivity of 1,4-benzodiazepine-based CCK(2) antagonists. In contrast to the latter compounds, these novel 1,3,4-benzotriazepines are achiral, yet they display similar affinity for CCK(2) receptors to the earlier molecules and are highly selective over CCK(1) receptors.

A structural and magnetic study of organolanthanide(III) amides.

The syntheses, structures and magnetic properties of the series of dimeric organolanthanide(III) amides [Cp2Ln{2-NH-4,6-Me2pm}]2 [Ln = Nd (1), Gd (2), Dy (3), Yb (4) and pm = pyrimidine], which are formed from the deprotonation of 2-amino-4,6-dimethylpyrimidine by the corresponding lanthanide tris-cyclopentadienide, are reported. The synthesis and structure of [{Cp2Yb(2-NH-4-MeO-6-MeOpm)(2)(mu3-O)(YbCp)] (5), formed in a similar deprotonation reaction but in the presence of adventitious water, is also reported.

Structural and magnetic studies of the tris(cyclopentadienyl)manganese(II) "paddle-wheel" anions [Cp(3-n)(MeCp)(n)Mn](-) (n=0-3, MeCp=C(5)H(4)CH(3), Cp=C(5)H(5)).

The ion-contact complexes [{(eta(5)-Cp)(2)Mn(eta(2):eta(5)-Cp)K}(3)]x0.5 THF (1x0.5 THF) and [{(eta(2)-Cp)(2)(eta(2);eta(5)-MeCp)MnK(thf)}]x2 THF (2x2 THF) and ion-separated complexes [Mg(thf)(6)][(eta(2)-Cp)(3)Mn](2) (3), [Mg(thf)(6)][(eta(2)-Cp)(eta(2)-MeCp)(2)Mn)](2)x0.5 THF (4x0.5 THF), [Mg(thf)(6)][(eta(2)-MeCp)(3)Mn)](2)x0.5 THF (5x0.5 THF) and [Li([12]crown-4)](5)[(eta-Cp)(3)Mn](5) (6) (Cp=C(5)H(5), CpMe=C(5)H(4)CH(3)), have been prepared and structurally characterised. The effects of varying the Cp and CpMe ligands in complexes 1-5 have been probed by variable-temperature magnetic susceptibility measurements and EPR spectroscopic studies.

cis-Eudesmane sesquiterpene glycosides from Liriope muscari and Ophiopogon japonicus.

Two new cis-eudesmane sesquiterpene glycosides, liriopeoside A (1) and ophiopogonoside A (2), were extracted and purified from tubers of Liriope muscari and Ophiopogon japonicus, respectively, along with three known compounds. Their structures were elucidated as 1beta,6beta-dihydroxy-cis-eudesm-3-ene-6-O-beta-D-glucopyranoside (1) and 1beta,4beta,6beta-trihydroxy-cis-eudesmane-6-O-beta-D-glucopyranoside (2) by spectral data analysis. The structure and the relative configuration of compound 1 were confirmed by X-ray crystallographic analysis. This is the first time that cis-eudesmane-type sesquiterpenes have been reported from the genera Ophiopogon and Liriope.

Suggestion of a "twist" mechanism in the oligomerisation of a dimeric phospha(III)zane: insights into the selection of adamantoid and macrocyclic alternatives.

The reaction of the dimeric phospha(III)zane [ClP(mu-Npy)]2 (1) (py = 2-pyridyl) with pyNHLi (2:1 equivalents, respectively) in THF/Et3N leads to rapid formation of the bicyclic nona-phospha(III)zane [[ClP(Npy)2]2-[P2(Npy)]] (2). This novel rearrangement can be rationalised by a mechanism involving "twisting (or swivelling)" of the central P(mu-Npy)P fragment of the presumed intermediate [[ClP(mu-Npy)2P]2(mu-Npy)] (3), a process that provides a fundamental mechanistic relationship between the majority of previously reported imidophosphospha(III)zanes. This process is fundamentally reliant on relief from ring strain on going from the four-membered ring units of 3 to the six-membered units of 2. The rearrangement observed for 1 is suppressed on steric grounds by Me-substitution of the pyridine ring at the 6-position, the dimeric phosphazane [ClP(mu-N-6-Me-py)]2 (4) (6-Me-py = 6-methyl-2-pyridyl) being formed almost exclusively in the 1:1 reaction of PCl3 with 6-Me-pyNHLi. The syntheses and X-ray structures of 1, 2 and 4 are reported, together with 31P NMR spectroscopic and DFT calculational studies of the conversion of models of 1 into 2. The combined studies pinpoint relief from ring strain as the key factor dictating the rearrangement.

Taraxer-14-en-3beta-ol, an anti-inflammatory compound from Sterculia foetida L.

Taraxer-14-en-3beta-ol ( 1) was shown to be the active ingredient in the leaves of Sterculia foetida L. The alcohol 1, its acetate and ketone showed anti-inflammatory activity against TPA induced mouse ear oedema with inhibition ratios of 60.0, 58.57 and 40.57 at 0.5 mg/ear, respectively. The percentage inhibition of inflammation increased with dose for each compound.

Templating and selection in the formation of macrocycles containing [[P(micro-NtBu)(2)](micro-NH)](n) frameworks: observation of halide ion coordination.

Amination of [ClP(micro-NtBu)](2) (1) using NH(3) in THF gives the cyclophospha(III)zane dimer [H(2)NP(micro-NtBu)](2) (2), in good yield. (31)P NMR spectroscopic studies of the reaction of 1 with 2 in THF/Et(3)N show that almost quantitative formation of the cyclic tetramer [[P(micro-NtBu)](2)(micro-NH)](4) (3) occurs. The remarkable selectivity of this reaction can (in part) be attributed to pre-organisation of 1 and 2, which prefer cis arrangements in the solid state and solution. The macrocycle 3 can be isolated in yields of 58-67 % using various reaction scales. The isolation of the major by-product of the reaction (ca. 0.5-1 % of samples of 3), the pentameric, host-guest complex [[P(micro-NtBu)(2)](2)(micro-NH)](5)(HCl).2 THF] (4.2 THF), gives a strong indication of the mechanism involved. In situ (31)P NMR spectroscopic studies support a stepwise condensation mechanism in which Cl(-) ions play an important role in templating and selection of 3 and 4. Amplification of the pentameric arrangement occurs in the presence of excess LiX (X=Cl, Br, I). In addition, the cyclisation reaction is solvent- and anion-dependent. The X-ray structures of 2 and 4.2 THF are reported.