New briaranes from the octocorals Briareum excavatum (Briareidae) and Junceella fragilis (Ellisellidae)

Six 12-hydroxybriaranes, including four new diterpenoids, briaexcavatins I-L (1-4), and two known metabolites, excavatolides C (5) and E (6), have been isolated from the cultured scleraxonia Briareum excavatum. In addition, the gorgonian coral Junceella fragilis yielded a new chlorinated briarane, fragilide C (10). The structures of above compounds were determined by spectroscopic methods and the structures of 5 and 6 were further confirmed by X-ray data analysis for the first time. The absolute configuration of 6 was elucidated by chemical conversion. Some of these briaranes have displayed inhibitory effects on superoxide anion generation by human neutrophils.     

Ten new antifouling briarane diterpenoids from the South China Sea gorgonian Junceella juncea

Ten new antifouling briarane diterpenoids, juncins R-ZI (1-10) were isolated from the South China Sea gorgonian coral Junceella juncea. The structures of these new compounds were established by extensive spectroscopic analysis, including 1D and 2D NMR data. Compounds 1-10 all showed potent antifouling activities against the larval settlement of barnacle Balanus amphitrite at nontoxic concentrations with EC₅₀ values of 0.004, 0.34, 2.65, 1.61, 3.77, 21.06, 0.004, 0.14, 1.47, and 0.51 μg mL⁻¹. The structure-activity relationship was discussed.     

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.     

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.     

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.     

Synthesis and properties of novel 5-(cyclohepta-2′,4′,6′-trienylidene)pyrimidine-2(1H),4(3H),6(5H)-triones: methodology for synthesizing cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborates

Novel condensation reaction of tropone with N-substituted and N,N′-disubstitued barbituric acids in Ac₂O afforded 5-(cyclohepta-2′,4′,6′-trienylidene)pyrimidine-2(1H),4(3H),6(5H)-trione derivatives (8a-f) in moderate to good yields. The ¹³C NMR spectral study of 8a-f revealed that the contribution of zwitterionic resonance structures is less important as compared with that of 8,8-dicyanoheptafulvene. The rotational barriers (ΔG^‡) around the exocyclic double bond of mono-substituted derivatives 8a-c were obtained to be 14.51-15.03 kcal mol⁻¹ by the variable temperature ¹H NMR measurements. The electrochemical properties of 8a-f were also studied by CV measurement. Upon treatment with DDQ, 8a-c underwent oxidative cyclization to give two products, 7 and 9-substituted cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborates (11a-c·BF₄⁻ and 12a-c·BF₄⁻) in various ratios, while that of disubstituted derivatives 8d-f afforded 7,9-disubstituted cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborate (11d-f·BF₄⁻) in good yields. Similarly, preparation of known 5-(1′-oxocycloheptatrien-2′-yl)-pyrimidine-2(1H),4(3H),6(5H)-trione derivatives (14a-d) and novel derivatives 14e,f was carried out. Treatment of 14a-c with aq. HBF₄/Ac₂O afforded two kinds of novel products 11a-c·BF₄⁻ and 12a,c·BF₄⁻ in various ratios, respectively, while that of 14d-f afforded 11d-f. The product ratios of 11a-c·BF₄⁻ and 12a-c·BF₄⁻ observed in two kinds of cyclization reactions were rationalized on the basis of MO calculations of model compounds 20a and 21a. The spectroscopic and electrochemical properties of 11a-f·BF₄⁻ and 12a-c·BF₄⁻ were studied, and structural characterization of 11c·BF₄⁻ based on the X-ray crystal analysis and MO calculation was also performed.     

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.     

Novel polyisoprenylated benzophenone derivatives from Garcinia paucinervis

Four novel polyisoprenylated benzophenone derivatives, paucinones A-D (1-4), were isolated from the leaves of the plant Garcinia paucinervis. Paucinones A-C (1-3) contained an unexpected cyclohexane-spiro-tetrahydrofuran moiety. A 1-methylene-3,3-dimethylcyclohexane group never reported before was found in the structure of paucinone D (4). The structures of these compounds were elucidated with spectroscopic evidences. The relative stereochemistries of 1-4 were determined by NOESY correlations. These compounds showed significant cytotoxicities against HeLa cells.     

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.     

Eight new limonoids from Turraea pubescens

Eight new ring B-seco limonoids, turrapubesic acids A-C (1-3) and turrapubesins C-G (4-8), along with turraflorin E and isoazadironolide were isolated from the twigs and leaves of Turraea pubescens. Turrapubesic acids A-C (1-3) are a group of ring B-seco limonoid 17-carboxylic acids with a new C₂₃ skeleton, and turrapubesin C (4) incorporates an unprecedented 1,30-oxygen bridge. The structures including absolute stereochemistry of 1-8 were established on the basis of extensive NMR spectroscopic analysis and CD study. The cytotoxicity of the isolates against the P-388 and A-549 cells was evaluated.     

Facile synthesis of 4-phenylquinolin-2(1H)-one derivatives from N-acyl-o-aminobenzophenones

An efficient synthesis of 4-phenylquinolin-2(1H)-one derivatives has been achieved in a one-pot reaction from N-acyl-o-aminobenzophenones 1a-c (a: acyl=acetyl; b: acyl=propanoyl; c: acyl=heptanoyl) using NaH as a base. Treatment of 1 with NaH provided the quinolones 2a-c with 62-83% yields, whereas the reaction in the presence of alkyl iodide (alkyl=methyl, ethyl, n-octyl) gave the corresponding N-alkylated quinolones 3a-g in 75-95% yields. The alkylation reaction of 4-phenylquinolin-2(1H)-one 2a with alkyl halide gave a mixture of N-alkylated and O-alkylated products. Comparison of IR and NMR data of the N-alkylated and O-alkylated compounds with those of 2a-c indicated that 2a-c exist as the lactam form.     

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.     

Substituent-induced regioselective synthesis of 1,2-teraryls and pyrano[3,4-c]pyran-4,5-diones from 2H-pyran-2-ones

Substituent-controlled regioselective synthesis of highly functionalized 1,2-teraryls 3a-k has been achieved through ring transformation of 6-aryl-4-(pyrrolidin-1-yl/piperidin-1-yl)-2H-pyran-2-one-3-carbonitriles 1a-g by aryl acetones 2a-c in the presence of powdered KOH in DMF in very good yield. Under similar reaction conditions, 6-aryl-4-methylsulfanyl-2H-pyran-2-ones 5a-f afforded 1,7-diaryl-2-methyl-4H,5H-pyrano[3,4-c]pyran-4,5-diones 6a-j as major products and 3,4-diaryl-2-methyl-6-methylsulfanylbenzonitriles as minor constituents 7a-j.     

Synthesis and rearrangement of cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-8/9-ones: an access to cycloalkyl[1,2-d]oxazolo[3,2-a]pyrimidin-5-ones

2-Substituted-4a-hydroxy-9H-cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-9-ones 2a-c were synthesized by an one-step cyclocondensation from the 5-substituted-2-amino-2-oxazolines 1a-c with ethyl 2-oxocyclohexanecarboxylate in ethanol at room temperature, and easily dehydrated to provide 2-substituted-9H-cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-9-ones 3. In refluxing xylene, the reaction conducted with various ethyl 2-oxocycloalkanecarboxylates led to the two isomeric 2-substituted-8/9H-cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-8/9-ones 3 and 2-substituted-5H-cycloalkyl[1,2-d]oxazolo[3,2-a]pyrimidin-5-ones 4. The structure of some compounds was unambiguously established using X-ray crystallography. According to results from the DSC analysis of compound 2a, formation of the thermodynamically stable pyrimidinones 4 could be related to an intramolecular rearrangement of kinetically controlled pyrimidinones 3.     

Agelasines O-U, new diterpene alkaloids with a 9-N-methyladenine unit from a marine sponge Agelas sp.

New diterpene alkaloids, agelasines O-U (1-7), have been isolated from an Okinawan marine sponge Agelas sp. The gloss structures and relative stereochemistries of 1-7 were elucidated from the spectroscopic data. Agelasines O-R (1-4) were the third examples of diterpene alkaloid with a 9-N-methyladenine and a pyrrole units. Agelasine O (1) has a halimane skeleton, while agelasines P-R (2-4) have a clerodane skeleton. Agelasines S-U (5-7) were new diterpene alkaloids with a 9-N-methyladenine unit consisting of a halimane skeleton, a labdane skeleton, and a clerodane skeleton, respectively. Agelasines O-R (1-4) and T (6) showed antimicrobial activities against several bacteria and fungi.     

Calyciphyllines H-M, new Daphniphyllum alkaloids from Daphniphyllum calycinum

Six new Daphniphyllum alkaloids, calyciphyllines H-M (1-6), were isolated from the leaves and stems of Daphniphyllum calycinum (Daphniphyllaceae). The structures and relative stereochemistry of 1-6 were elucidated on the basis of spectroscopic data, and the absolute stereochemistry of 3 was assigned by PGME method.     

Further syphonosides from the sea hare Syphonota geographica and the sea-grass Halophila stipulacea

The unusual structural features of syphonoside (1), recently reported from the marine mollusc Syphonota geographica and its prey Halophila stipulacea, stimulated further investigations on the minor secondary metabolites of both organisms. The three novel macrocyclic glycoterpenoids 2-4, structurally related to the main co-occurring metabolite 1, have been isolated and chemically characterized mainly by NMR spectroscopic techniques and degradation methods. Compounds 2 and 3 were found only in the mollusc whereas compound 4 was isolated in trace quantities exclusively from the sea-grass.     

Psoracorylifols A-E, five novel compounds with activity against Helicobacter pylori from seeds of Psoralea corylifolia

Five novel compounds, psoracorylifols A-E (1-5) with important activity against Helicobacter pylori have been isolated from a well-known traditional Chinese medicine (TCM), the seeds of Psoralea corylifolia. The structures of compounds 1-5, including their absolute configurations, were established on the basis of spectral methods and biogenetic reason. The structure of 1 was confirmed by a single-crystal X-ray diffraction. Psoracorylifols D and E (4 and 5) represent an unprecedented carbon skeleton. The biogenetic origin of psoracorylifols A-E (1-5) was also postulated.     

Synthesis of 2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)-ones by the domino Michael addition retro-ene reaction of 2-alkoxyiminoimidazolidines and acetylene carboxylates

2-Alkoxyiminoimidazolidines 2-3 react with acetylene dicarboxylates and ethyl phenylpropiolate to give 8-alkoxy-imidazo[1,2-a]pyrimidin-5(3H)-ones C, which subsequently undergo a sterically induced multihetero-retro-ene fragmentation to give imidazo[1,2-a]pyrimidin-5(1H)-ones 4-7 together with formaldehyde or benzaldehyde. On the other hand, a similar reaction of 2-3 with ethyl propiolate gives corresponding 8-alkoxy-imidazo[1,2-a]pyrimidin-5(3H)-ones 8-10. The unsubstituted imidazo[1,2-a]pyrimidin-5(1H)-one 11 can be prepared by retro-ene reaction of 9 upon prolonged heating in refluxing ethanol. A direct synthetic approach to 1-formyl-7-phenyl-imidazo[1,2-a]pyrimidine-5(1H)-one 14 is reported using DMF/sulfonyl chloride as a new Vilsmeier-type N-formylating reagent.     

Isolation and characterization of miscellaneous terpenoids of Schisandra chinensis

Two new bisnortriterpenoids with 18-norschiartane skeleton, wuweizidilactones G (1) and H (2), four new highly oxygenated nortriterpenoids based on a schisanartane skeleton, schindilactones D-G (3-6), a pre-schisanartane skeleton, pre-schisanartanin B (7), and a novel 3,4-seco-21,26-olide-artane triterpenoid wuweizilactone acid (8), along with 24 known terpenoids with different carbon frameworks, have been isolated from the acetone extract of the stems and leaves of Schisandra chinensis. The terpenoids produced by this plant have chemical diversity. The structures of new compounds 1-8 have been characterized by spectroscopic data interpretation. The cytotoxicity and anti-HIV-1 activity of all the Schisandra nortriterpenoids were evaluated.