Velutabularins A-J, phragmalin-type limonoids with novel cyclic moiety from Chukrasia tabularis var. velutina

Velutabularins A-J, ten novel phragmalin-type limonoids, were isolated from the stem bark of Chukrasia tabularis var. velutina. In structures of 1-6, the tetrahydrofuran ring from dehydration of OH-15 and OH-17, ring C and 13/14/18-cyclopropanyl moiety formed an unprecedented 8-oxatricyclo[4,3,1^1,6]decane. Compounds 7-10 are derivates of 1-6 opening the tetrahydrofuran ring. All of these compounds possess a novel C-16/C-30 δ-lactone ring, which were reported in phragmalins rarely. The structures of these novel compounds were elucidated based on extensive 1D and 2D spectroscopic analysis. The absolute configuration of 5 and 9 were determined by the calculated electronic circular dichroism (ECD) method. The anti-inflammatory activities of major compounds (2, 4, 5, 9) were evaluated for inhibitory activity against lipopolysaccharide (LPS) induced nitric oxide (NO) production in macrophage (RAW264.7) cell line.     

Diterpenoids from Isodon pharicus

A phytochemical investigation of Isodon pharicus led to the isolation of a novel asymmetric ent-kauranoid dimer, bispseurata F (1), and three new diterpenoids, pharicinins A-C (2-4). Their structures were elucidated by extensive spectroscopic analysis. Compound 1 features a unique linkage pattern of C-17 with C-11′ to connect the two monomers. A possible biogenetic pathway of 1 was also proposed. Compounds 3 and 4 exhibited moderate inhibitory activity against NB4 and SH-SY5Y cell lines.     

New tricyclic geldanamycin analogues from an engineered strain of Streptomyces hygroscopicus JCM4427

Two tricyclic geldanamycin analogues, DHQ5 (1) and DHQ6 (2), were produced by a combinatorial mutant (AC15) contained a site-directed mutagenesis on the geldanamycin polyketide synthase (PKS) gene with inactivation of the post-PKS tailoring genes (gel7) of Streptomyces hygroscopicus JCM4427. The structural diversity of tricyclic geldanamycin analogues is due to the formation of unusual additional rings, which are formed by alkylation of the C-21 position by C-12 in DHQ5 (1) and by electrophilic addition of the C-15 hydroxyl group to the double bond (C-8-C-9), which leads to the migration of the double bond (to C-7-C-8) and the elimination of a carbamoyloxy group in DHQ6 (2).     

Revisiting diterpene lactones of Suregada multiflora

Phytochemical investigations on the organic extracts of the leaves of Suregada multiflora have led to the isolation of ten tetracyclic diterpene lactones 1-10, members of a rare class of abiatene diterpene lactones. Compounds 1-5 were found to be new. The structures of gelomulides F (11), D (12) and E (13) were revised on the basis of 2D NMR and X-ray diffraction evidences. Compounds 1 and 2 contain an epoxy linkage between C-8 and C-14, whereas compounds 3-5 were identified as 8,14-dihydroxy analogues of diterpene lactones. The stereochemical assignments in new compound 1 are based on X-ray diffraction analysis. Compounds 6 and 7 were identified as the known gelomulides A, G. The structures of compounds 7-9 were unambiguously confirmed by X-ray diffraction analyses.     

Novel sesquiterpenes and norergosterol from the soft corals Nephthea erecta and Nephtheachabroli

Chemical investigations on the acetone extract of the Formosan soft coral Nephthea erecta have afforded a new calamenene-type sesquiterpene with a mercaptan group at C-15, erectathiol (1), and a previously reported sesquiterpenoid, (+)-trans-calamenene (2). A novel sec-germacrane sesquiterpene (3), along with a novel norergosterol, chabrosterol (4), possessing a 19-norergostane skeleton, was isolated from the other soft coral Nephthea chabroli. The structures of these metabolites were elucidated through extensive spectroscopic analyses. In vitro anti-inflammatory activity of 1 and 4 (10 μM) significantly reduced the levels of the iNOS protein (58.0 ± 6.5% and 12.4 ± 2.9%) and COX-2 protein (108.7 ± 4.5% and 45.2 ± 5.4%). In addition, metabolite 1 (166 μg/disk) exhibited antimicrobial activities against a small panel of bacterial strains.     

Anti-Pseudomonas aeruginosa xanthones from the resin and green fruits of Cratoxylum cochinchinense

Cochinchinones I-L (1-3 and 13) along with 11 known xanthones (4-12, 14, and 15) were isolated from the resin and green fruits of Cratoxylum cochinchinense. In addition, four new acetylated compounds (16-19) were derivatized from 7-geranyloxy-1,3-dihydroxyxanthone (14) and 3-geranyloxy-1,7-dihydroxyxanthone (15). All compounds were characterized on the basis of spectroscopic analyses. The structures of cochinchinone I (1), a monoacetate (18) and a dibrosylate (20), were also confirmed by X-ray diffraction analysis. The antibacterial and antifungal activities of selected compounds were evaluated as well.     

Synthesis of (4R,15R,16R,21S)- and (4R,15S,16S,21S)-rollicosin

A convergent synthesis of (4R,15R,16R,21S)-rollicosin (1) and (4R,15S,16S,21S)-rollicosin (2) was accomplished. Hydroxy lactone 6a and/or 6b were synthesized from 4-pentyn-1-ol, and α,β-unsaturated lactone 7 was synthesized from γ-lactone 8 and 5-hexen-1-ol. Inhibitory activity of these compounds was examined with bovine heart mitochondrial complex I.     

3,4-seco-Diterpenoids from Trigonostemon flavidus

Phytochemical investigation on the stems of Trigonostemon flavidus resulted in the isolation of five new 3,4-seco-diterpenoids, trigoflavidones A-E (1-5), structurally related to the main co-occurring known 3,4-seco-sonderianic acid (6) and 3,4-seco-sonderianol (7). Compound 4 possesses new 3,4-seco rearranged ent-pimarane skeletal type, characteristic of a vinyl group at C-8, while 5 features a unique five-membered ring (C₁) fused with a cyclopropane ring (C₂). The structures of the new compounds were established by a combination of spectroscopic data and computational methods. Compounds 1-7 were tested for their cytotoxicities on HL-60, SMMC-7721, A-549, MCF-7, and SW480 human tumor cell lines.     

Two novel 3,4-seco-trinorlanostane triterpenoids isolated from Ganoderma fornicatum

Two novel 3,4-seco-25,26,27-trinorlanostane triterpeniod compounds, fornicatins A and B (1 and 2) have been isolated from the fruiting body of G. fornicatum. The structural elucidation of 1 and 2 were accomplished by extensive NMR analysis. The relative stereochemistry of 2 was established by single crystal X-ray crystallography, which also confirmed the novel carbon skeleton of the new triterpenoid. An ether linkage of C-4 with C-7 in 1 is unprecedented in natural triterpenoids. Both compounds were tested for their inhibitory effects on rabbit platelet aggregation induced by PAF, ADP, or AA.     

Bisleuconins A-D: a pair of epimeric ent-kauranoid dimers and two new asymmetric analogues isolated from Isodonleucophyllus

A phytochemical investigation of Isodon leucophyllus led to the isolation of four novel ent-kauranoid dimers: bisleuconins A-D (1-4), and one known compound, rabdoloxin A (5). It was interesting that the structures of bisleuconins A (1) and B (2) were elucidated as a pair of epimeric ent-kauranoid dimers with unique linkage pattern C-16→C-17′ to connect two monomers. Bisleuconins C (3) and D (4) were two new asymmetric ent-kauranoid dimers. A possible biogenetic pathway of 1 and 2 was also proposed.     

Five novel norcembranoids from Sinularia leptoclados and S. parva

Three new norcembrane-based diterpenoids, leptocladolides A (1), B (4) and C (5), along with five known metabolites 6-10, have been isolated from the dichloromethane extract of a Taiwanese soft coral Sinularia leptoclados. Furthermore, a chemical investigation on the dichloromethane extract of S. parva has resulted in the isolation of two new related isomers, 1-epi-leptocladolide A (2) and 7E-leptocladolide A (3), in addition to 1 and 7. The structures of new metabolites 1-5 were elucidated on the basis of extensive spectroscopic analyses and their relative stereochemistries were determined by NOESY experiments. The new metabolites 1 and 3 have been shown to exhibit significant cytotoxic activity against KB and Hepa59T/VGH cancer cell lines.     

Muchimangins E and F: novel diphenylmethyl-substituted xanthones from Securidaca longepedunculata

Two new highly oxygenated xanthones, named muchimangins E (1) and F (2), have been isolated from the root of Securidaca longepedunculata (Polygalaceae). Their structures were elucidated by the analyses of spectral data to be a novel xanthone with a diphenylmethyl substituent at C-2. Moreover, the structures of muchimangins B (4) and C (5) were revised by careful analysis of the spectral data and by comparing their NMR data with those of 1 and 2, to be xanthones with the diphenylmethyl substituent at C-2, not at C-4 reported previously.     

Three lanostane triterpenoids with antitrypanosomal activity from the fruiting body of Hexagonia tenuis

During the search for new antitrypanosomal drug leads, three new antitrypanosomal compounds, hexatenuins A–C (1–3), were isolated from the fruiting body of Hexagonia tenuis. 1 and 3 possessed an unusual malonate half-ester functional group at C-3 position, and 1 and 2 had a spirostructure in the side-chain. Their structures were elucidated using MS analyses, extensive 2D-heteronuclear NMR data interpretation. Compounds 1–3 showed in vitro antitrypanosomal activity against Trypanosoma brucei brucei with IC₅₀ values of 0.57, 8.60 and 5.62 μg/ml, respectively.     

New oxindole and indole alkaloids from Gelsemium rankinii

Six new humantenine-type (1-6) and two new gelsemine-type (7, 8) oxindole alkaloids and one new indole alkaloid (9) were isolated from the leaves and branches of Gelsemium rankinii. The structures of the new alkaloids were determined by spectroscopic analyses. Among them, 6-hydroxyhumantenine (5) is the first example of a Gelsemium alkaloid with an oxygen function at C-6 position, and is a plausible biogenetic precursor of gelsemine-type alkaloids.     

Cytotoxic cuparene sesquiterpenes from Laurencia microcladia

Three new cuparene sesquiterpenes 1-3 were isolated from the organic extract of the red alga Laurencia microcladia, collected at Chios island in the North Aegean Sea, Greece. The structures and the relative stereochemistry of the compounds are proposed on the basis of their spectral data. Metabolite 2 shows an unprecedented (for the cuparene class of sesquiterpenes) migration of the C-1 methyl group. All metabolites 1-3 were found to exhibit significant cytotoxic activity against two lung cancer cell lines.     

Gelegamines A-E: five new oxindole alkaloids from Gelsemium elegans

Five new oxindole alkaloids, gelegamines A-E (1-5), were isolated from the roots of Gelsemium elegans. Their structures were extensively elucidated on the basis of spectroscopic analysis. Among them, the epoxy ring (C-19/C-20) of gelegamine A (1) was assigned as α-orientation by ROESY experiment and DFT method at B3LYP/6-31g(d) level, and gelegamine B (2) is the first humantenine-type alkaloid with 19-(E) ethylidene configuration. The absolute configurations of gelegamines A-E (1-5) were established on biosynthetic consideration coupled with CD experiments.     

6,7-Seco-ent-kaurane-type diterpenoids from Isodon eriocalyx var. laxiflora

Twenty nine 6,7-seco-ent-kaurane-type diterpenoids including 18 new ones, laxiflorolides C–T (1–18), along with 21 known ones were obtained from Isodon eriocalyx var. laxiflora. Laxiflorolides E–G (3–5) are the first identified naturally occurring 6,7-seco-ent-kauranoids that feature a 3,6-epoxy unit, and laxiflorolide M (11) is the first identified naturally occurring 6-nor-6,7-seco-ent-kauranoid. The absolute configurations of compounds 1, 3, 6, and 11 were determined by single-crystal X-ray diffraction analyses. The cytotoxic activity of the isolates was evaluated by an MTT assay.     

Cannabioxepane, a novel tetracyclic cannabinoid from hemp, Cannabis sativa L.

Apart from large amounts of cannabidiol, the known stilbenoids 1-4 and the oxylipins 7 and 8, a fibre cultivar of Cannabis sativa derived from the historical Carmagnola variety gave the novel spiranic stilbenoid isocannabispiradienone (5) and the biphenyl-type cannabinoid cannabioxepane (CBX, 6), a tetracyclic compound characterized by an unprecedented C-5/C-8′ oxygen bridge and devoid of cannabinoid activity. Structures were established by analysis of MS and NMR data, and the biogenetic derivation of the new compounds is discussed.     

Lyconadins C and F, new Lycopodium alkaloids from Lycopodium complanatum

New Lycopodium alkaloids, lyconadins C (1) and F (2), were isolated from the club moss Lycopodium complanatum. Lyconadin C (1) is a new C₁₆N₂-type Lycopodium alkaloid possessing unique fused-tetracyclic ring system consisting of a cycloheptene ring fused to a decahydroquinoline and pyridone rings. Lyconadin F (2) possesses a primary amide moiety in its molecular, which is the first example of Lycopodium alkaloids. Biogenetically, lyconadins C (1) and F (2) might be related to lyconadins A (4) and B (5). The structures and relative stereochemistry of 1 and 2 were elucidated on the basis of spectroscopic data. The absolute stereochemistry of 2 was elucidated by chemical correlations with lyconadin B (5) through hemiaminal form of lyconadin F (3).     

New polyesters from Talaromyces flavus

Six new polyesters, talapolyesters A–F (1–4, 14, and 16), together with 11 known ones 15G256ν (5), 15G256ν-me (6), 15G256π (7), 15G256β-2 (8), 15G256α-2 (9), 15G256α-2-me (10), 15G256ι (11), 15G256β (12), 15G256α (13), 15G256α-1 (15), and 15G256ω (17), were isolated from the wetland soil-derived fungus Talaromyces flavus BYD07-13, and their structures were determined by NMR and MS spectroscopic data. Among them, 1–4 and 16 were assembled in a different manner from that of the known 256 polyesters. All the polyesters are composed of (R)-2,4-dihydroxy-6-(2-hydroxypropyl)benzoic acid and (R)-3-hydroxybutyric acid/(S)-3,4-dihydroxybutyric acid residues. The absolute configurations of the residues were determined by alkaline hydrolysis. The cytotoxicity against five tumor cell lines of these compounds was examined, and a tight structure–activity relationship is proposed.