Ternatusine A, a New Pyrrole Derivative with an Epoxyoxepino Ring from <i>Ranunculus ternatus</i>

Ternatusine A (<b>1</b>), a novel alkaloid with an unprecedented epoxyoxepino[4,5-<i>c</i>] pyrrole ring, was isolated from the roots of <i>Ranunculus ternatus</i> Thunb. Its unusual structure, including its absolute stereochemistry, was determined using UV, IR, HRESIMS, and 1D and 2D NMR data and through comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. A possible biosynthetic pathway for ternatusine A was postulated

Polyflavanostilbene A, a New Flavanol-Fused Stilbene Glycoside from <i>Polygonum cuspidatum</i>

Polyflavanostilbene A, a new flavanol-fused stilbene glycoside, was isolated from the rhizome of <i>Polygonum cuspidatum</i>. Its unusual structure, including its absolute stereochemistry, was determined by UV, IR, HRESIMS, and 1D and 2D NMR data and by the comparison of experimental and calculated electronic circular dichroism (ECD) spectra. Polyflavanostilbene A has an unprecedented rearranged flavanol skeleton fused to stilbene via a hexahydrocyclopenta[<i>c</i>]furan moiety. Polyflavanostilbene A showed strong inhibitory activity against α-glucosidase with an IC₅₀ value of 17.7 μM

Structures of WS070117 metabolites in rat urine and the proposed metabolic pathways.

<p>Structures of WS070117 metabolites in rat urine and the proposed metabolic pathways.</p

The retention time, predicted elemental compositions, observed mass and calculated mass, characteristic fragment ions, and description of metabolites of WS070117 in rat urine.

<p>The retention time, predicted elemental compositions, observed mass and calculated mass, characteristic fragment ions, and description of metabolites of WS070117 in rat urine.</p

¹H NMR derived HSQC (A) and HMBC (B) spectra of <i>N</i>₈-hydroxy-<i>N</i>₆-(3-<i>O</i>-sulfophenyl) adenine (structure see formula insert).

<p><b>A</b> secondary metabolite in rat urine following WS070117 oral administration. The NMR spectra were obtained in deuterated DMSO on a 500 MHz NMR spectrometer, equipped with a 1.7 PA TXI microprobe. (A) HSQC (acquisition time: 2 h): red cross-peaks are stemming from CH, CH₂ and CH₃ protons. (B) HMBC (acquisition time: 6 h): the correlation information derived from the marked cross-peaks is summarized in the formula insert.</p

HPLC chromatogram of WS010117 metabolites in urine of control (A) and administrated (B) rats at 299 nm.

<p>Peak 1: 3.60 min (M1); 2: 14.15 min (M2); 3: 21.58 min (M3); 4: 23.25 min (M4); 5: 29.48 min (M5); 6: 47.68 min (M6); 7: 48.73 min (M7); 8: 49.44 min (M8).</p

The stack of ¹³C NMR spectra of WS010117 and its four metabolites (in DMSO-d₆).

<p>The stack of ¹³C NMR spectra of WS010117 and its four metabolites (in DMSO-d₆).</p

Structure Elucidation of the Metabolites of 2', 3', 5'-Tri-<i>O</i>-Acetyl-<i>N</i>₆-(3-Hydroxyphenyl) Adenosine in Rat Urine by HPLC-DAD, ESI-MS and Off-Line Microprobe NMR

<div><p>2', 3', 5'-tri-<i>O</i>-acetyl-<i>N₆</i>-(3-hydroxyphenyl) adenosine (also known as WS070117) is a new adenosine analog that displays anti-hyperlipidemic activity both <i>in vitro</i> and <i>in vivo</i> experiments as shown in many preliminary studies. Due to its new structure, little is known about the metabolism of WS070117. Hence, the <i>in vivo</i> metabolites of WS070117 in rat urine following oral administration were investigated. Identification of the metabolites was conducted using the combination of high-performance liquid chromatography (HPLC) coupled with diode array detector (DAD), ion trap electrospray ionization-mass spectrometry (ESI-MS), and off-line microprobe nuclear magnetic resonance (NMR) measurements. Seven metabolites were obtained as pure compounds at the sub-milligram to milligram levels. Results of structure elucidation unambiguously revealed that the phase I metabolite, <i>N₆</i>-(3-hydroxyphenyl) adenosine (M8), was a hydrolysate of WS070117 by hydrolysis on the three ester groups. <i>N₆</i>-(3-hydr-oxyphenyl) adenine (M7), also one of the phase I metabolites, was the derivative of M8 by the loss of ribofuranose. In addition to two phase I metabolites, there were five phase II metabolites of WS070117 found in rat urine. 8-hydroxy-<i>N₆</i>-(3-hydroxy-phenyl) adenosine (M6) was the product of M7 by hydrolysis at position 8. The other four were elucidated to be <i>N₆</i>-(3-<i>O-β</i>-D-glucuronyphenyl) adenine (M2), <i>N₈</i>-hydroxy-<i>N₆</i>-(3-<i>O</i>-sulfophenyl) adenine (M3), <i>N₆</i>-(3-<i>O-β</i>-D-glucuronyphenyl) adenosine (M4), and <i>N₆</i>-(3-<i>O</i>- sulfophenyl) adenosine (M5). Phase II metabolic pathways were proven to consist of hydroxylation, glucuronidation and sulfation. This study provides new and valuable information on the metabolism of WS070117, and also demonstrates the HPLC/MS/off-line microprobe NMR approach as a robust means for rapid identification of metabolites.</p></div

Hepatoprotective Dibenzocyclooctadiene and Tetrahydrobenzocyclooctabenzofuranone Lignans from <i>Kadsura longipedunculata</i>

Five new dibenzocyclooctadiene lignans, longipedlignans A–E (<b>1</b>–<b>5</b>), five new tetrahydrobenzo­cyclooctabenzo­furanones (<b>6</b>–<b>10</b>), and 18 known analogues (<b>11</b>–<b>28</b>) were isolated from the roots of <i>Kadsura longipedunculata</i>. Compounds <b>6</b>–<b>10</b> are new spirobenzofuranoid–dibenzocyclooctadiene-type lignans. Their structures and absolute configurations were established using a combination of MS, NMR, and electronic circular dichroism data. Spirobenzofuranoids <b>6</b> and <b>15</b> showed moderate hepatoprotective activity against <i>N</i>-acetyl-<i>p</i>-aminophenol-induced toxicity in HepG2 cells with cell survival rates at 10 μM of 52.2% and 50.2%, respectively