Feroniellides A and B, apotirucallane triterpenes with novel cyclic acetals from Feroniella lucida

The isolation and structure elucidation of two new triterpenes named feroniellides A (1) and B (2) from Feroniella lucida are described. Feroniellide A has a novel dioxabicyclic [3.2.1]octane moiety, and feroniellide B is the C-3 epimer of the known triterpenoid 3. Their overall structures and relative configurations were established by combined spectral data analysis. The cytotoxicity of 1 and 2 was also evaluated against human KB and HeLa carcinoma cells.     

Solvent-free reactions of N,N′-thiocarbonyldiimidazole with ferrocenylcarbinols

The efficient and simple routes for the synthesis of various ferrocenyl derivatives from ferrocenylcarbinols and N,N′-thiocarbonyldiimidazole (TCDI) are described. It involves grinding the two substrates in a Pyrex tube with a glass rod at room temperature. The reaction of ferrocenylmethanol (1a) provided S,S-bis(ferrocenylmethyl)dithiocarbonate (1b), whose crystal structure and a plausible mechanism for its formation are also reported. The reaction of 1-ferrocenyl-1-phenylmethanol (2a) and 1-ferrocenylbutanol (2b) gave the products 2c and 2d, respectively. The reaction of ω-ferrocenyl alcohols 4-ferrocenylphenol (3a) and 6-ferrocenylhexan-1-ol (3b) yielded the products 3c and 3d, respectively. Reaction of 1,1′-ferrocenedimethanol (3e) afforded 3f in moderate yield, and by contrast, it was not similar to 1b. Reaction of [4-(trifluoromethyl)phenyl]methanol (4a) provided the thiocarbonate 4b in good yield.     

Absolute configuration of gomadalactones A, B and C, the components of the contact sex pheromone of Anoplophora malasiaca

Absolute configuration of gomadalactones A (1), B (2) and C (3), the pheromone components of the white-spotted longicorn beetle (Anoplophora malasiaca) was assigned as (1S,4R,5S)-1, (1R,4R,5R)-2 and (1S,4R,5S,8S)-3 by comparing their published CD spectra with those of (1R,5R)-(+)-4,4,8-trimethyl-3-oxabicyclo[3.3.0]oct-7-ene-2,6-dione (4) and (1S,5R,8S)-(+)-4,4,8-trimethyl-3-oxabicyclo[3.3.0]octane-2,6-dione (5) prepared from (R)-(−)-carvone (6).     

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.     

Synthesis and properties of 4,9-methanoundecafulvenes and their transformation to 3-substituted 7,12-methanocycloundeca[4,5]furo[2,3-d]pyrimidine-2,4(1H,3H)-diones: photo-induced autorecycling oxidizing reaction toward amines

The synthesis and properties of 4,9-methanoundecafulvene [5-(4,9-methanocycloundeca-2′,4′,6′,8′,10′-pentaenylidene)pyrimidine-2,4,6(1,3,5H)-trione] derivatives 8a,b were studied. Their structural characteristics were investigated on the basis of the ¹H and ¹³C NMR and UV-vis spectra. The rotational barrier (ΔG^‡) around the exocyclic double bond of 8a was found to be 12.55 kcal mol⁻¹ by the variable temperature ¹H NMR measurement. The electrochemical properties of 8a,b were also studied by CV measurement. Furthermore, the transformation of 8a,b to 3-substituted 7,12-methanocycloundeca[4,5]furo[2,3-d]pyrimidine-2,4(1H,3H)-diones 16a,b was accomplished by oxidative cyclization using DDQ and subsequent ring-opening and ring-closure. The structural details and chemical properties of 16a,b were clarified. Reaction of 16a with deuteride afforded C13-adduct 19 as the single product, and thus, the methano-bridge controls the nucleophilic attack to prefer endo-selectivity. The photo-induced oxidation reaction of 16a and a vinylogous compound, 3-methylcyclohepta[4,5]furo[2,3-d]pyrimidine-2,4(3H)-dione 2a, toward some amines under aerobic conditions were carried out to give the corresponding imines (isolated by converting to the corresponding 2,4-dinitrophenylhydrazones) with the recycling number of 6.1-64.0 (for 16a) and 2.7-17.2 (for 2a), respectively.     

Synthesis, molecular structure, and chemical reactivity of azuleno[1,2-a]acenaphthylene

The azuleno[1,2-a]acenaphthylene (1a) was prepared from 1-pyrrolidinylacenaphthylene (5) and 2H-cyclohepta[b]furan-2-one (6) by the method of the Takase-Yasunami azulene synthesis. Its ¹H and ¹³C NMR spectra indicate that 1a comprises azulene and naphthalene rather than acenaphtylene and heptafulvene in accordance with speculation drawn from a previous study of the DEPE calculations. The solid-state structure of 1a was elucidated by X-ray crystallographical analysis, indicating that 1a is nearly planar and exhibits little bond alternation as seen in the optimized structure at the MB3LYP/6-311G^∗ level of theory. All bond lengths observed by the X-ray analysis are in good agreement within 0.024 Å with those calculated. Under pyrolytic conditions 1a underwent azulene-naphthalene rearrangement to give 9 and 10. The electrophilic substitution of 1a was observed at the 7-position and the second reaction at the 3-position. The cycloaddition reaction of 1a with dimethyl acetylenedicarboxylate (DMAD) yielded the 1:1 cycloadduct with a heptalene skeleton 16a and the 1:2 cycloadduct 19, along with the substitution product 17. The X-ray structural analysis of the cycloadducts 16a and 19 is also described.     

trans-Spanning ferrocene amidodiphosphine ligand: Synthesis, palladium complexes and catalytic use in Suzuki-Miyaura cross-coupling

Amide coupling between [2-(diphenylphosphino)phenyl]methylamine and 1′-(diphenylphosphino)ferrocene-1-carboxylic acid (Hdpf) afforded a novel diphosphine-amide, 1-{N-[(2-(diphenylphosphino)phenyl)methyl]carbamoyl}-1′-(diphenylphosphino)ferrocene (1), which was subsequently studied as a ligand for palladium(II) complexes. Depending on the metal precursor, the following complexes were isolated: [PdCl₂(1-κ²P,P′)] (2), [PdCl(Me)(1-κ²P,P′)] (3), [(μ-1){PdCl₂(PBu₃)}₂] (4) and [(μ-1){PdCl(L^NC)}₂] (L^NC = 2-[(dimethylamino-κN)methyl]phenyl-κC¹), featuring this ligand either as a trans-chelating or as a P,P′-bridging donor. The crystal structure of 2·1.25CH₂Cl₂ was established by X-ray crystallography, corroborating that 1 coordinates as a trans-spanning diphosphine without any significant distortion to the coordination sphere. Complex 2 together with a catalyst prepared in situ from 1 and palladium(II) acetate were tested in Suzuki-Miyaura reaction of aryl bromides with phenylboronic acid in dioxane.     

PhP-PPh group bound to 1,8-positions of naphthalene: Preparation of cis isomer and synthesis of binuclear complex

A thermodynamically less stable cis isomer of 1,2-diphosphacycle was prepared from the corresponding trans isomer. Diphosphine, in which a PhP-PPh bond bridges the 1,8-positions of naphthalene, 1,2-diphenyl-1,2-dihydronaphtho[1,8-cd][1,2]diphosphole (1), was first prepared according to a previously reported method, and the trans isomer of 1 was irradiated in tetrahydrofuran with UV-vis light to reach equilibrium with cis-1 in a trans:cis ratio of 1:2. When a similar photochemical conversion was carried out using a saturated hexane solution of trans-1, cis-1 was precipitated in a good yield of 94%. The configuration of cis-1 was confirmed by X-ray analysis. Both cis- and trans-1 diphosphine ligands were used for the preparation of binuclear gold complexes. The crystal structure of (μ-cis-1)-[AuCl]₂ demonstrated that the two lone pairs of cis-1 are suitably directed for arrangement of the two gold centers in close proximity to each other. The two independent (μ-cis-1)-[AuCl]₂ molecules in the crystal were found to form a dimer through the multiple intermolecular interaction among the gold centers.     

An unusual indole alkaloid with anti-adenovirus and anti-HSV activities from Alstonia scholaris

A novel alkaloid, 17-nor-excelsinidine (1), possessing an unusual 1-azoniatricyclo [4.3.3.0] undecane moiety was isolated from the twigs and leaves of Alstonia scholaris alongside its biogenetically related strictamine (2). The structure and absolute stereochemistry of compound 1 were rigorously determined by a combination of NMR spectroscopy and X-ray crystallography. The 17-nor-excelsinidine (1) and strictamine (2) showed significant inhibitory activity against herpes simplex virus (HSV) and adenovirus (ADV).     

Cyclic tetrapeptides from marine bacteria associated with the seaweed Diginea sp. and the sponge Halisarca ectofibrosa

A Pseudomonas sp. was cultured which was associated with the Japanese seaweed Diginea sp. Crude extracts prepared from this bacterial culture were found to inhibit the growth of other marine bacterial strains. From this bacterial culture, two new peptides cyclo-[phenylalanyl-prolyl-leucyl-prolyl] (3) and cyclo-[isoleucyl-prolyl-leucyl-alanyl] (4) have been isolated together with two known peptides (1) and (2). The crude extract from a culture of Pseudoalteromonas sp. associated with the Thai sponge Halisarca ectofibrosa was found to inhibit the growth of Bacillus subtilis and Vibrio anguillarum. Isolation studies yielded a fraction containing two peptides that were identified as cyclo-[phenylalanyl-leucyl]₂ (5) and cyclo-[leucyl-isoleucyl]₂ (6) by means of LC-MS and 2D NMR data. Absolute stereochemistry was confirmed by the synthesis of cyclo-[l-phenylalanyl-l-leucyl]₂. Peptides (1)-(3) were also isolated from this bacterial strain. None of the individual peptides isolated in this study showed antibiotic activity.     

Photoinduced cycloadditions of N-methyl-1,8-naphthalenedicarboximides with alkynes

Photoinduced cycloadditions of N-methyl-1,8-naphthalenedicarboximide 1 with phenylacetylenes 2a-2c, cyclopropylacetylene 2d, diphenylacetylenes 2e-2f and 1-phenylpropyne 2g were investigated. In the case of phenylacetylenes 2a, 2b and cyclopropylacetylene 2c, photoreaction with 1 takes place at the naphthalene C(1)C(2) bond to give the cyclobutene products. For 4-methoxyphenylacetylene 1c, the cyclobutene 3c is obtained together with the 4-benzo[a]thebenidinone 4c derived from a primary oxetene product formed by [2+2] addition of the imide carbonyl with the alkyne. Similar to 2c, photocycloaddition of 1 with 2e and 2f gave the cyclobutenes 7e, 7f, 8f and the 4-benzo[a]thebenidinone products 9e, 9f and 10f, respectively, derived from the corresponding oxetenes. Photoreaction of 1 with 2g gave cyclobutene 7g and benzo[a]thebenidinone 9g. Sensitization experiment and internal heavy atom effect study showed that these reactions proceed from the ππ* singlet excited state of 1. Estimation of the free energy change for electron transfer between ¹1* and the alkynes and the calculation of charge and spin density distribution in the anion radical of 1 and the cation radical of the alkynes suggested that the cyclobutene products are formed by direct [2+2] cycloaddition of ¹1* with the alkyne, while the formation of the oxetene products is the result of electron transfer interaction between ¹1* and the alkyne. The regioselectivity in the oxetene formation is accounted for by charge and spin density distribution in the anion radical of 1 and the cation radical of the alkyne.     

Reactions of some anellated 2-aminothiophenes with electron poor acetylenes

The reactivity of 2-aminothiophenes in two different anellations: (a) [b]-anellation to a saturated carbocycle and (b) [3,4-c]-anellation to benzopyrans, towards typical acetylenic dienophiles has been investigated. Because of the absence of conjugation, the thiophenes of type (a) do not undergo [4+2]-cycloaddition with acetylenic dienophiles. Instead, the N-vinylated products 2 and 3 were obtained with dimethyl acetylene dicarboxylate (DMAD). Electron poor alkynes react with the thiophenes of type (b) in three main ways: DMAD reacts in a [4+2]-mode in dioxane to give the products 7, 8 and 14; a Michael addition type reaction also takes place at the doubly vinylene homologous carbon atoms (C-1 in the starting materials 4, 9 and 10) in dioxane, methanol or ethanol. Methyl propiolate reacts in a similar way. The doubly N-vinylated product 26 was obtained from 10 in toluene and the C-1 vinylated products 24B and 27 were obtained from 9 in dioxane and 10 in methanol. The reaction of 10 with phenyl ethyl propiolate in dimethylformamide gave no addition product, instead a dimer of the acetylenic reagent was the isolated product. The accuracy of the assigned structures 5, 12 and 13a could be achieved on the basis of a single-crystal X-ray structure analysis of compound 13a. The reaction mechanism and the nature of the isolated products are dependent on the nature of the solvent. No addition reaction was observed between 17 and DMAD. The influence of the N-substitution on the nature of the addition (Michael or Diels-Alder) could be settled through the reactions of 18 and 21 with DMAD, which gave 19 and 14 (via 22), respectively as the only isolable products.     

Amarusine A,a new dioxaspiro[4.4]nonane derivative with a butyrolactone ring from Pleioblastus amarus

Amarusine A (1), a new polyketide derivative possessing an unusual dioxaspiro[4.4]nonane derivative with a butyrolactone ring, was isolated from the leaves of Pleioblastus amarus. The structure and absolute stereochemistry of compound 1 were rigorously determined using UV, IR, HRESIMS, and 1D and 2D NMR techniques and by comparing experimental and calculated electronic circular dichroism (ECD) spectra. Amarusine A (1) exhibits a good antioxidant activity for scavenging the DPPH radical. A possible biosynthetic pathway was postulated.     

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.     

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.     

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.     

Trichiol and 3-epitrichiol acetate, novel cytotoxic sterols with an unprecedented 2,6-dioxabicyclo[2.2.2]octan-3-one ring system from the myxomycete Trichia favoginea var. persimilis

Trichiol (1) and 3-epitrichiol acetate (2), two new sterols, have been isolated from field-collected fruit bodies of the myxomycete, Trichia favoginea var. persimilis, and their structures elucidated by spectral data. Trichiol (1) and 3-epitrichiol acetate (2) possess an unprecedented 2,6-dioxabicyclo[2.2.2]octan-3-one ring system. Trichiol (1) was cytotoxic against HeLa cells, while compound 2 proved to exhibit reversal effect against TNF-related apoptosis inducing ligand (TRAIL)-resistant Jurkat cell lines.     

Bacilosarcins A and B, novel bioactive isocoumarins with unusual heterocyclic cores from the marine-derived bacterium Bacillus subtilis

Two novel isocoumarins, bacilosarcins A (1) and B (2) were isolated from a culture broth of the marine-derived bacterium Bacillus subtilis TP-B0611. The structures and absolute configurations of 1 and 2 were determined on the basis of spectroscopic analyses and chemical conversions. Compound 1 possesses an unprecedented 3-oxa-6,9-diazabicyclo[3.3.1]nonane ring system while 2 has a 2-hydroxymorpholine moiety that is rare in nature. These compounds showed growth inhibition against barnyard millet.     

Short-step syntheses and complexation properties of Z,Z-tribenzodidehydro- and all-Z-tribenzo[12]annulenes

Syntheses of all-Z-tribenzo[12]annulenes (1a-c) and Z,Z-tribenzodidehydro[12]annulenes (2a-c) by the reduction of the corresponding tribenzohexadehydro[12]annulenes 3a-c were carried out using a low valent titanium complex generated from Ti(O-i-Pr)₄ and i-PrMgCl. The unique structure of the first reduction products 2a-c as well as 1a-c was fully characterized. Complexation of these annulenes with silver(I) ions produces the corresponding silver complexes. Among them, the silver complexes of 2a-c exhibit interesting monomer-dimer equilibrium.     

An expedient, regioselective synthesis of 2-alkylamino- and 2-alkylthiothiazolo[5,4-e]indoles

1-Benzenesulfonyl-5-aminoindole 5, prepared from 5-nitroindole 3, was condensed with alkyl isothiocyanates and separately with carbon disulfide and alkyl bromides/iodides to furnish efficiently the corresponding N-alkyl-thioureidoindoles 6a-c and the alkyl N-(indol-5′-yl)dithiocarbamates 9a-e, respectively. Their cyclisation using N-bromosuccinimide (NBS) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), in the cold, followed by indolic N-deprotection, furnished regioselectively the 2-alkylamino- and the 2-alkylthiothiazolo[5,4-e]indoles 8a-c and 11a-e, respectively, in good overall yields.