Search

(±)-Hypeisoxazole A (1), a racemic pair of rearranged benzylisoquinoline alkaloids possessing an unprecedented diindeno[2,1-c:2′,1′-d] isoxazole scaffold, was isolated from the medicinal herb Hypecoum erectum, along with hypecoleptopine (2), whose structure is now revised as a novel spiro-benzylisoquinoline alkaloid with a 6/6/5/6/6 skeleton. Their structures were determined by comprehensive spectroscopic and spectrometric analyses, X-ray diffraction, and computational studies. Racemic mixture of 2and its pure enantiomers modulated neuronal excitability activity.

Alternarin A (1), a rearranged drimane meroterpenoid characterized by a thioglycerate moiety, was isolated together with two known analogues from the coral-associated fungi Alternariasp. ZH-15. Its structure was determined based on spectroscopic analysis, modified Mosher’s method, and TDDFT/ECD calculations. In a primary cultured cortical neuronal network, compound 1effectively inhibited the activity of spontaneous synchronous Ca2+oscillations and 4-aminopyridine induced epileptic discharges in the low micromolar concentration range.

The new phthalideisoquinoline hemiacetal alkaloids (2–7) and the known analogues (1and 8) were isolated from the bulbs of Corydalis decumbens. The new compounds were characterized by analysis of their NMR spectroscopic data, chemical degradation syntheses, X-ray crystallography, and comparison of experimental and calculated ECD data. All the isolates were screened in vitro for inhibitory activity of spontaneous calcium oscillations in primary cultured neocortical neurons. Compounds 1–3and 5–7were found to be active in the suppression of spontaneous calcium oscillations with IC50values of 6.8, 5.6, 11.6, 10.2, 8.3, and 3.1 μM, respectively. It was also observed that the presence of hydroxy, methoxy, and ethoxy groups at the remote stereogenic center C-7′ of some isolated phthalideisoquinoline hemiacetal alkaloids could alter the preferred conformation and invert the sign of optical rotation, rather than this resulting from configurational isomerism at C-1 or C-9, and that the 3J1,9coupling constants of these analogues varied accordingly. For example, compounds 1and 6are levorotatory, despite these molecules having the same carbon skeleton and absolute configuration as (+)-egenine. This emphasizes the potential risk of incorrectly assigning absolute configuration based only on observed coupling constants or optical rotation when comparing the data of new compounds with literature values for known analogues, especially within this class of molecules.

Six new iridal-type triterpenoids containing an unprecedented cyclopentane ring, polycycloiridals E–J (1–6), were isolated from a large-scale re-extraction of Iris tectorum. A possible biosynthesis pathway is postulated. The known spirioiridotectal D (7) was also obtained in the current investigation, and its structure was unequivocally defined using X-ray diffraction data. Compound 7suppressed LPS-activated NO production in the BV2 cell line with an IC50value of 0.54 μM.

Territrem F (1), a drimane meroterpenoid bearing a unique borate ring system, was isolated together with its diol precursor territrem B (2) from the fungus Alternariasp. ZH-15 associated with the soft coral Lobophytum crassumcollected in the South China Sea. The structure of the new compound was elucidated by spectroscopic analysis and an X-ray single-crystal diffraction study, representing a new type of boron-containing natural product. Both compounds significantly inhibited spontaneous synchronous Ca2+oscillations (SCOs) and epileptic discharges induced by 4-aminopyridine, showing the potential for antiepileptic drug research. The 5,9-boronic ester derivative of 2did not change its SCO inhibitory activity.

We identified and characterized a malate dehydrogenase from Streptomyces coelicolorA3(2) (ScMDH). The molecular mass of ScMDH was 73,353.5 Da with two 36,675.0 Da subunits as analyzed by matrix-assisted laser-desorption ionization–time-of-flight mass spectrometry (MALDI-TOF-MS). The detailed kinetic parameters of recombinant ScMDH are reported here. Heat inactivation studies showed that ScMDH was more thermostable than most MDHs from other organisms, except for a few extremely thermophile bacteria. Recombinant ScMDH was highly NAD+-specific and displayed about 400-fold (kcat) and 1,050-fold (kcat⁄Km) preferences for oxaloacetate reduction over malate oxidation. Substrate inhibition studies showed that ScMDH activity was inhibited by excess oxaloacetate (Ki=5.8 mM) and excess L-malate (Ki=12.8 mM). Moreover, ScMDH activity was not affected by most metal ions, but was strongly inhibited by Fe2+and Zn2+. Taken together, our findings indicate that ScMDH is significantly thermostable and presents a remarkably high catalytic efficiency for malate synthesis.

Thirteen new benzamide alkaloids, delphiniumines A–M (1–13), together with one known analogue (14), were isolated from Delphinium anthriscifoliumHance. All of the structures were determined by spectroscopic and spectrometric analyses. Absolute configuration for 1was established using experimental and calculated ECD data, as well as by X-ray crystallography analysis. Compound 1possesses a previously undescribed polysubstituted cyclopentene carbon framework. Compound 2was isolated as an artifact from 1during the extraction process. Compound 7is glycosylated with a β-D-glucose unit. Compound 13bears a chlorine substituent. At a concentration of 10 μM, compounds 6, 8, and 10–12suppressed LPS-induced NO production in RAW264.7 cells with inhibition rates ranging from 40.3% to 78.8%.

Nine new cadinane sesquiterpenoids, alanenses A–I (1–9), were isolated from the leaves of Alangium chinensetogether with three previously reported analogues (10–12). The structures of these molecules were elucidated by interpretation of spectroscopic and spectrometric data. Absolute configurations were established by the comparison of experimental and calculated ECD data, chemical degradation studies for sugar moieties, and a single-crystal X-ray diffraction analysis. Compounds 1and 2were isolated as racemates, and enantiopurification was achieved by chiral HPLC. Compounds 3–5are glycosylated cadinanes bearing a β-d-glucose unit, while compounds 6–9incorporate a hydroxymethyl group in either the free form or additional ring fusion. The structure of compound 11was originally misassigned and later revised using additional NMR data. The corrected structure is here supported by X-ray single-crystal analysis. Compounds 1and 2inhibit spontaneous calcium channel oscillations at low micromolar concentrations.