Structures of new alkaloids sessilifoliamides A-D from Stemona sessilifolia

Four new Stemona alkaloids, sessilifoliamides A-D (1-4), were isolated from the roots of Stemona sessilifolia, along with five known alkaloids, stenine (5), 2-oxostenine (6), stemoninoamide (7), tuberostemonone (8), and neotuberostemonol (9). The structures and absolute configurations of the new alkaloids were determined by the spectral studies (HRMS, IR, ¹H, ¹³C, and 2D NMR), single-crystal X-ray analyses, and chemical correlations. The absolute configuration of 7 was also determined by the modified Mosher's method.     

Acyclic tertiary diamines and 1,4,7,10-tetraazacyclododecane with fluorine-containing β-diketones: Leading to low melting ionic adducts

N,N,N′,N′-Tetramethylmethanediamine (1a), N,N,N′,N′-tetramethylethanediamine (1b), N,N,N′,N′-tetramethyl-1,3-propanediamine (1c), and N,N,N′,N′-tetramethyl-1,6-hexanediamine (1d) were reacted at 25 °C with 1,1,1,5,5,5-hexafluoro-2,4-pentanedione (2a), 2,2-dimethyl-6,6,7,7,8,8,8-heptafluoro-3,5-octanedione (2b), 2-thenoyltrifluoroacetone (2c), and 4,4,4-trifluoro-1-(2-furyl)-1,3-butanedione (2d) to form the ionic adducts 3-18. 1,4,7,10-Tetraazacyclododecane (1e) reacted at 25 °C with β-diketones (2a-d) and 1,1,1-trifluoro-2,4-pentanedione (2e) to give ionic solids 19-23 in good yields. Some of the products are liquid at 25 °C and are thermally stable over long liquid ranges as determined by thermal gravimetric analyses. Single-crystal X-ray structure determinations show that compounds 9 and 21 crystallize in the monoclinic space groups P2(1)/c and P2(1)/n, respectively. All the new compounds were characterized by ¹H, ¹⁹F and ¹³C NMR, electrospray MS and/or elemental analyses.     

Synthesis of functional Δ-1,3,5-oxazaphospholene and 2H-1,4,2-diazaphosphole complexes via catalytic ring expansion reactions of a 2H-azaphosphirene complex

Catalytically-induced ring expansion of 2H-azaphosphirene complex 1 using ferrocenium hexafluorophosphate and acetone (2), diethylketone (3), cyclohexanone (4), benzaldehyde (5) or para-hydroxy-benzaldehyde (6) furnished selectively the Δ³-1,3,5-oxazaphospholene complexes 7-11, whereas with ortho- and para-hydroxy- or ortho- and para-amino-substituted benzonitriles the 2H-1,4,2-diazaphosphole complexes 16-19 were obtained. Two further findings are noteworthy: (1) The significant decreased reaction time in the case of the sterically more demanding carbonyl derivatives 2-4 and (2) the formation of diastereomers in the case of 10 and 11 with a ratio of 8:1 and 9:1, respectively. All products were characterized by NMR, MS and elemental analysis and the configuration of complexes 7 and 10a were determined by X-ray single-crystal diffraction analysis.     

Alkaloids and citrinins from marine-derived fungus Nigrospora oryzae SCSGAF 0111

A new pyrrolidinone, nigrospine (1), a new indole alkaloid, nigrospin A (2) and two new citrinins, nigrospins B and C (3-4) were isolated from a culture broth of the marine-derived fungal strain Nigrospora oryzae SCSGAF 0111. Their structures were determined by spectroscopic analysis, and the absolute configurations of 1 and 2 were determined by the Mosher ester technique. Compound 1 contains a rare 2,3-dihydro-benzofuran[2,3-c]2-pyrrolidone skeleton.     

Tabularisins A-D, phragmalin ortho esters with new skeleton isolated from the seeds of Chukrasia tabularis

Tabularisins A-D (1-4), a new class of phragmalins incorporating a cyclopropanyl ring, were isolated from Chukrasia tabularis. Compounds 1 and 2 are also the first examples of phragmalins with an 8,9,11-ortho ester. The structures of 1 and 3 were confirmed by single crystal X-ray studies. The absolute configuration of 2 was determined by CD exciton chirality method on its benzoate (2a), and those of 1, 3, and 4 were proposed by correlating with 2 chemically and biogenetically.     

Stabilization of (N-methyleneamino)imidoylketenes: synthesis of dipyrazolo[1,2-a;1′,2′-d][1,2,4,5]tetrazines

Thermolysis of substituted methyl 1-methyleneamino-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates 2a,b led to substituted dimethyl 3,9-dioxo-1,5,7,11-tetrahydro-1H,7H-dipyrazolo[1,2-a;1′,2′-d][1,2,4,5]tetrazine-1,7-dicarboxylates 4a,b and methyl 2,5-dihydro-5-oxo-1H-pyrazole-3-carboxylates 5a,b as minor products. The structure of compound 4a was determined by X-ray crystallography. The proposed mechanism of this conversion includes generation of (N-methyleneamino)imidoylketenes 6a,b and its intramolecular transformation to azomethine imines—5-oxo-2,5-dihydropyrazole-1-methylium-2-ides 7a,b, which undergo dimerization in head-to-tail manner yielding products 4a,b and partially hydrolyse to compounds 5a,b.     

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.     

Novel alkaloids, paxdaphnines A and B with unprecedented skeletons from the seeds of Daphniphyllum paxianum

Two novel Daphniphyllum alkaloids with unprecedented skeletons, namely paxdaphnines A (1) and B (2), have been isolated from the seeds of Daphniphyllum paxianum. Paxdaphnine A (1) is a 19-nor-Daphniphyllum alkaloid with highly caged skeleton, and paxdaphnine B (2) is the first 1,19-bisnor-Daphniphyllum alkaloid. The relative structures of 1 and 2 were elucidated by spectral methods, and their unique biosynthetic pathway postulated. The absolute structure of 1 was determined by X-ray diffraction of the iodide derivative (1a) of 1, and the absolute stereochemistry of 2 was proposed by correlation with the biosynthetic pathway for 1.     

Preparation of new pyrido[3,4-b]thienopyrroles and pyrido[4,3-e]thienopyridazines

Two new types of pyrido-fused tris-heterocycles (1a,b and 2a,b) have been prepared from 3-aminopyridine in five/six steps. A synthetic strategy for the preparation of the novel pyrido[3,4-b]thieno[2,3- and 3,2-d]pyrroles (1a,b) and pyrido[4,3-e]thieno[2,3- and 3,2-c]pyridazines (2a,b) has been studied. The Suzuki cross coupling of the appropriate 2- and 3-thienoboronic acids (3,4) and 4-bromo-3-pyridylpivaloylamide (9) afforded the biaryl coupling products (10,11) in high yields (85%). Diazotization of the hydrolysed (2-thienyl)-coupling product (12) and azide substitution gave the 3-azido-4-(2-thienyl)pyridine intermediate (72%, 14). 3-Azido-4-(3-thienyl)pyridine (15) was prepared by exchanging the previous order of reactions. The desired β-carboline thiophene analogues (1a,b) were obtained via the nitrene by thermal decomposition of the azido precursors (14,15). By optimising conditions for intramolecular diazocoupling, the corresponding pyridazine products (72-83%, 2a,b) were afforded.     

Feroniellins A-C, novel cytotoxic furanocoumarins with highly oxygenated C10 moieties from Feroniella lucida

Three new furanocoumarins, named feroniellins A (1), B (2), and C (3), were isolated from the roots of Feroniella lucida. Compounds 1-3 are novel structures having an oxolane, oxane, and oxepane moiety. Their overall structures and configurations were determined by spectral and chemical methods. The cytotoxicities of 1-3 were evaluated against human KB and HeLa carcinoma cells.     

Bioactive pregnane-type steroids from the soft coral Scleronephthya gracillimum

Nine new steroids, sclerosteroids A-I (1, 5, 6, 8-13), along with 18 known metabolites (2-4, 7, 14-27), were isolated from the soft coral Scleronephthya gracillimum. These structures were elucidated on the basis of detailed spectroscopic analysis. The absolute configurations of sugar moieties in steroidal glycosides 10-13 were determined by HPLC analysis of the o-tolylthiocarbamate derivatives of the liberated sugars from hydrolysis of these steroidal giycosides. Cytotoxic and anti-inflammatory activities of these compounds were measured in vitro.     

Dopamine derivatives from the insect Polyrhachis dives as inhibitors of ROCK1/2 and stimulators of neural stem cell proliferation

Polyrhachis dives is consumed as an insect food in some regions of China. In this study, new dopamine derivatives, (+)-polyrhadopamine A (1a) and (−)-polyrhadopamine A (1b), (+)-polyrhadopamine B (2a) and (−)-polyrhadopamine B (2b), and polyrhadopamines C–E (3–5), were isolated from this species. The structures and stereochemistry of these substances were assigned by using spectroscopic and computational methods. Compounds 1a, 1b, 2a, and 2b are dimeric N-acetyldopamine derivatives, 3 is a dopamine analog containing an unusual sulfone group, and 4 and 5 possess a rare benzo[d]thiazole moiety. The functions of these substances as ROCK1/2 inhibitors, neural stem cell (NSCs) proliferation stimulators, immunosuppressive, and anti-inflammatory agents were determined.     

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.     

Dimolybdenum complexes containing anions of N,N′-bis(pyrimidine-2-yl)formamidine and N-(2-pyrimidinyl)formamide

The reactions of Mo₂(O₂CCH₃)₄ with different equivalents of N,N′-bis(pyrimidine-2-yl)formamidine (HL1) and N-(2-pyrimidinyl)formamide (HL2) afforded dimolybdenum complexes of the types Mo₂(O₂CCH₃)(L1)₂(L2) (1) trans-Mo₂(L1)₂(L2)₂ (2) cis-Mo₂(L1)₂(L2)₂ (3) and Mo₂(L2)₄ (4). Their UV–Vis and NMR spectra have been recorded and their structures determined by X-ray crystallography. Complexes 2 and 3 establish the first pair of trans and cis forms of dimolybdenum complexes containing formamidinate ligands. The L1 ligands in 1–3 are bridged to the metal centers through two central amine nitrogen atoms, while the L2 ligands in 1–4 are bridged to the metal centers via one pyrimidyl nitrogen atom and the amine nitrogen atom. The Mo–Mo distances of complexes 1 [2.0951(17) Å], 2 [2.103(1) Å] and 3 [2.1017(3) Å], which contain both Mo?N and Mo?O axial interactions, are slightly longer than those of complex 4 [2.0826(12)–2.0866(10) Å] which has only Mo?O interactions.     

New microviridins from a water bloom of the cyanobacterium Microcystis aeruginosa

Three new microviridins namely, SD1684 (1), SD1634 (2), and SD1652 (3), were isolated from the hydrophilic extract of Microcystis aeruginosa. The planar structures of compounds 1-3 were determined by homonuclear and inverse-heteronuclear 2D-NMR techniques as well as by high-resolution mass spectrometry. The absolute configuration of the asymmetric centers was studied using Marfey's method for HPLC. Compounds 1-3 contain l-threo-β-hydroxy aspartic acid as a building block of the peptide chain. This is the first example where microviridins contain non-proteinogenic amino acid in their structure. Compound 2 is a mild serine protease inhibitor.     

Briarenolides A-C, briarane diterpenoids from the gorgonian coral Briareum sp.

Chemical investigation on the gorgonian coral Briareum sp. has led to the isolation of six oxygenated briaran diterpenes 1-6, including three new compounds briarenolides A-C (1-3). The structures of 1-3 were determined on the basis of extensive spectroscopic analysis and by comparison of their spectral data with those of related metabolites. Among these metabolites, 1 and 2 are rarely found 9-ketobriaranes. Also, 1 is the first briarane derivative possessing a 20-hydroxy group.     

Microwave assisted synthesis of novel imidazo [2,1-b]thiazole derivative attached to quinoxalinones

3-(6-Phenylimidazo[2,1-b]thiazol-5-yl)quinoxalin-2(1H)-ones (qunoxalinone) (6a-q) have been synthesized by the reaction of ethyl 2-oxo-2-(6-phenylimidazo[2,1-b]thiazol-5-yl)acetates (4a-e) with suitably substituted o-phenylenediamines (5a-f) under microwave heating. The ethyl 2-oxo-2-(6-phenylimidazo[2,1-b]thiazol-5-yl)acetates (4a-e) were prepared by the reaction of 6-phenylimidazo[2,1-b]thiazoles (3a-e) with ethyl chlorooxoacetate in refluxing 1,4-dioxane whereas the thiazoles (3a-e) were synthesized by the reaction of 2-bromo-1-phenylethanones (2a-e) with thiazol-2-amine in refluxing acetone.     

Daphcalycinosidines A and B, new iridoid-alkaloids from Daphniphyllum calycinum

Three new alkaloids, daphcalycinosidines A (1) and B (2) and daphcalycic acid (3) have been isolated from the seeds of Daphniphyllum calycinum. The structures and relative stereochemistries were determined on the basis of spectral studies including 2D NMR, mass spectrometry and chemical transformations. Structures 1 and 2 are characterized by an iridoid glucoside moiety linked to new Daphniphyllum alkaloid moieties.     

Five new eremophilane derivatives from Ligularia sagitta

Ligulasagitins A-E (1-5), five new eremophilane-derived metabolites possibly formed via a Diels-Alder reaction in the biosynthetic process, were isolated from Ligularia sagitta Maxim. Among them 1 and 2 possess a novel C19 skeleton, 4 and 5 are two novel dimeric eremophilane type derivatives. Their structures were determined by extensive spectroscopic analysis and the structure of 2 was also confirmed by a single-crystal X-ray diffraction analysis. Furthermore, 4 and 5 showed weak cytotoxic activity against HL-60 (human promyelocytic leukemia) cells.     

Banchromene and other secondary metabolites from the endophytic fungus Fusarium sp. obtained from Piper guineense inhibit the motility of phytopathogenic Plasmopara viticola zoospores

A new chromene, (S)-banchromene (1), together with seven known compounds, ergosterol, beauvericin (2), fusaproliferin (3), radicinin (4), poly(3-hydroxybutyric acid) (PHB, 5), N-methylpyrrolidone and an inseparable mixture of isochromene derivatives 6a, 6b, were isolated from a culture of Fusarium sp. strain CAMKT24b1, an endophytic fungus from the leaves and twigs of Piper guineense (Piperaceae). The structures of these metabolites were elucidated on the basis of their spectroscopic data; the absolute configuration of 1 was determined by ab initio-calculation of the optical rotation. In tests with the zoospores of the grapevine downy mildew pathogen Plasmopara viticola, compounds 1–4 showed moderate to high levels of motility-impairing activity at concentrations as low as 2.5 μg/mL. Compound 2 was the most active, exhibiting both motility-halting and lytic activities. Furthermore, compounds 2 and 3 displayed significant cytotoxic activity against brine shrimp larvae (Artemia salina) at 10 μg/mL. This is the first report on motility inhibitory and lytic activities of metabolites from an endophytic Fusarium species against the zoospores of the downy mildew pathogen P. viticola.