Semisynthetic Preparation and Isolation of Dimeric Procyanidins B1–B8 from Roasted Hazelnut Skins (Corylus avellana L.) on a Large Scale Using Countercurrent Chromatography

Dimeric procyanidins B1–B8 were produced via semisynthesis from a polymeric proanthocyanidin fraction of hazelnut skins (Corylus avellana L.). This polymeric fraction was found to consist mostly of (+)-catechin and (−)-epicatechin as upper units. Therefore, according to the choice of nucleophile agent, it is possible to semisynthesize dimeric procyanidins B1, B3, B6, and B7 with (+)-catechin and B2, B4, B5, and B8 with (−)-epicatechin. The semisynthetic mixtures were separated on a preparative scale using high-speed countercurrent chromatography (HSCCC) and low-speed rotary countercurrent chromatography (LSRCCC). C4 → C8 linked dimeric procyanidins B1–B4 were isolated in amounts of 350–740 mg. To the best of the authors’ knowledge this is the first study isolating dimeric procyanidins B1–B8 in large amounts with countercurrent chromatography. Moreover, the dimeric prodelphinidins B1, B2, and B3 and their structural elucidation by ¹H NMR spectroscopy without derivatization are described for hazelnuts as natural compounds for the first time

Trimeric Anthracenes from the Endophytic Fungus <i>Stemphylium globuliferum</i>

The first naturally occurring trimeric anthracene derivatives, stemphylanthranols A and B (<b>1</b> and <b>2</b>), were obtained from the endophytic fungus <i>Stemphylium globuliferum</i> that had been isolated from <i>Juncus actus</i> growing in Egypt. The structures of the new compounds were unambiguously determined by 1D and 2D NMR, and by HRMS. A hypothetical biosynthetic pathway for the new trimers is proposed

New Cytotoxic 1,2,4-Thiadiazole Alkaloids from the Ascidian <i>Polycarpa aurata</i>

Two new alkaloids, polycarpathiamines A and B (<b>1</b> and <b>2</b>), were isolated from the ascidian <i>Polycarpa aurata</i>. Their structures were unambiguously determined by 1D, 2D NMR, and HRESIMS measurements and further confirmed by comparison with a closely related analogue, 3-dimethylamino-5-benzoyl-1,2,4-thiadiazole (<b>4</b>), that was prepared by chemical synthesis. Compounds <b>1</b> and <b>2</b> both feature an uncommon 1,2,4-thiadiazole ring whose biosynthetic origin is proposed. Compound <b>1</b> showed significant cytotoxic activity against L5178Y murine lymphoma cells (IC₅₀ 0.41 μM)

Balticidins A–D, Antifungal Hassallidin-Like Lipopeptides from the Baltic Sea Cyanobacterium Anabaena cylindrica Bio33

Balticidins A–D (<b>1</b>–<b>4</b>), four new antifungal lipopeptides, were isolated from the laboratory-cultivated cyanobacterium Anabaena cylindrica strain Bio33 isolated from a water sample collected from the Baltic Sea, Rügen Island, Germany. Fractionation of the 50% aqueous MeOH extract was performed by bioassay-guided silica gel column chromatography followed by SPE and repeated reversed-phase HPLC. The main fraction containing the compounds exhibited a strong and specific antifungal activity with inhibition zones in an agar-diffusion assay from 21 to 32 mm against Candida albicans, Candida krusei, Candida maltosa, Aspergillus fumigatus, Microsporum gypseum, Mucor sp., and Microsporum canis. The structures were elucidated by multidimensional ¹H and ¹³C NMR spectroscopy, HRESIMS, amino acid analysis, and sugar analysis. Spectroscopic data analysis afforded an unambiguous sequence of R.CHO­(S1).CHOH.CONH-Thr(1)-Thr(2)-Thr(3)-HOTyr(4)-Dhb(5)-d-Gln­(6)-Gly­(7)-NMeThr­(8)­(S2)-l-Gln <i>C</i>OOH­(9), in which Dhb is dehydro­aminobutyric acid, S1 is d­(−)-arabinose-(3-1)-d-(+)-galacturonic acid, S2 is d-(+)-mannose, and R is the aliphatic residue -C₁₃H₂₆Cl or -C₁₃H₂₇. Besides NMeThr, d-<i>allo</i>-Thr, d-Thr, and l-Thr were identified, but the position of the enantiomers in the sequence is not clear. The four balticidins differ in their cyclic (<b>2</b>, <b>4</b>)/linear (<b>1</b>, <b>3</b>) core and the presence (<b>1</b>, <b>2</b>)/absence (<b>3</b>, <b>4</b>) of chlorine in the aliphatic unit

Cytotoxic and Protein Kinase Inhibiting Nakijiquinones and Nakijiquinols from the Sponge <i>Dactylospongia metachromia</i>

Chemical investigation of the sponge <i>Dactylospongia metachromia</i> afforded five new sesquiterpene aminoquinones (<b>1</b>–<b>5</b>), two new sesquiterpene benzoxazoles (<b>6</b> and <b>7</b>), the known analogue 18-hydroxy-5-<i>epi</i>-hyrtiophenol (<b>8</b>), and a known glycerolipid. The structures of all compounds were unambiguously elucidated by one- and two-dimensional NMR and by MS analyses, as well as by comparison with the literature. Compounds <b>1</b>–<b>5</b> showed potent cytotoxicity against the mouse lymphoma cell line L5178Y with IC₅₀ values ranging from 1.1 to 3.7 μM. When tested <i>in vitro</i> for their inhibitory potential against 16 different protein kinases, compounds <b>5</b>, <b>6</b>, and <b>8</b> exhibited the strongest inhibitory activity against ALK, FAK, IGF1-R, SRC, VEGF-R2, Aurora-B, MET wt, and NEK6 kinases (IC₅₀ 0.97–8.62 μM)

Pro-Apoptotic and Immunostimulatory Tetrahydroxanthone Dimers from the Endophytic Fungus Phomopsis longicolla

Four tetrahydroxanthone dimers (<b>1</b>–<b>4</b>) and four biogenetically related monomers (<b>5</b>–<b>8</b>), including the new derivatives <b>4</b>–<b>6</b>, were isolated from the endophyte Phomopsis longicolla. The absolute configurations of <b>2</b>–<b>4</b> were established for the first time by TDDFT electronic circular dichroism calculations, and that of phomoxanthone A (<b>1</b>) was revised by X-ray crystallography. Phomoxanthone A (<b>1</b>) showed the strongest pro-apoptotic activity when tested against a panel of human cancer cell lines, including cisplatin-resistant cells, whereas it was up to 100-fold less active against healthy blood cells. It was also the most potent activator of murine T lymphocytes, NK cells, and macrophages, suggesting an activation of the immune system in parallel to its pro-apoptotic activity. This dual effect in combating cancer cells could help in fighting resistance during chemotherapy. Preliminary structure–activity studies of isolated compounds and derivatives obtained by semisynthesis (<b>9a</b>–<b>11</b>) hinted at the location of the biaryl axis and the presence of acetyl groups as important structural elements for the biological activity of the studied tetrahydroxanthones