Triterpene Saponins from the Aerial Parts of Trifolium medium L. var. sarosiense

Seven previously unreported triterpene glycosides (1−7) were isolated from methanol extract of the aerial parts of Trifolium medium var. sarosiense (zigzag clover). Their structures were established by the extensive use of 1D and 2D NMR experiments along with ESI-MS and HRMS analyses. Compounds 1−7 are oleanane derivatives characterized by the presence of a keto group at C-22 of an aglycone and a primary alcoholic function at C-24 and differing functions at C-30. Among these, compounds 1−3 and 6 showed a secondary alcoholic function at C-11, which is methoxylated in compounds 4 and 7. Compound 5 was shown to possess a known aglycone, wistariasapogenol A; however, it is described here for the first time as a saponin constituent of the Trifolium genus. Some aspects of taxonomic classification of zigzag clover are also discussed

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Phase stability of the earth-abundant tin sulfides SnS, SnS2, and Sn2S3

The various phases of tin sulfide have been studied as semiconductors since the 1960s and are now being investigated as potential earth-abundant photovoltaic and photocatalytic materials. Of particular note is the recent isolation of zincblende SnS in particles and thin-films. Herein, first-principles calculations are employed to better understand this novel geometry and its place within the tin sulfide multiphasic system. We report the enthalpies of formation for the known phases of SnS, SnS2, and Sn2S3, with good agreement between theory and experiment for the ground-state structures of each. While theoretical X-ray diffraction patterns do agree with the assignment of the zincblende phase demonstrated in the literature, the structure is not stable close to the lattice parameters observed experimentally, exhibiting an unfeasibly large pressure and a formation enthalpy much higher than any other phase. Ab initio molecular dynamics simulations reveal spontaneous degradation to an amorphous phase much lower in energy, as Sn(II) is inherently unstable in a regular tetrahedral environment. We conclude that the known rocksalt phase of SnS has been mis-assigned as zincblende in the recent literature

Two oleanene glycosides from the aerial parts of Caltha polypetala

Abstract: Two new oleanene glycosides (1–2) possessing hederagenin as the aglycone were isolated from the methanolic extract of the aerial parts of Caltha polypetala together with four known glycosides. The saccharide portion linked to C-3 of the aglycone is made up of α-l-arabinopyranose, α-l-rhamnopyranose and galactopyranose in the new compounds; while compound 1 possesses linked to C-28 a trisaccharide moiety made up of two β-d-glucopyranose and one α-l-rhamnopyranose unit, in compound 2 the 28-COOH group is free. The structures were elucidated by 1D and 2D NMR experiments including 1H–1H (DQF-COSY, 1D-TOCSY, 2D-ROESY) and 1H–13C (HSQC, HMBC) spectroscopy