Synthesis and odor of optically active trans-2,2,6-trimethylcyclohexyl methyl ketones and their related compounds

The synthesis characterized by cationic olefin cyclizations accomplished using ketone enol esters and odor of novel (1R,6S)- and (1S,6R)-2,2,6-trimethylcyclohexyl methyl ketones (5) are described. The stereoselective syntheses of (E)-(1R,6S)- and (E)-(1S,6R)-1-(2,2,6-trimethylcyclohexyl)-2-buten-1-one (6) and (1R,6S)-ethyl 2,2,6-trimethylcyclohexylcarboxylate (7), useful raw materials for flavor and fragrance, starting from the (1R,6S)- and (1S,6R)-5 are also described.     

Stereochemical challenges in characterizing nitrogenous spiro-axane sesquiterpenes from the Indo-Pacific sponges Amorphinopsis and Axinyssa

An investigation was conducted to identify the structures and bioactive properties of five compounds isolated from the Halichondrida sponges Amorphinopsis foetida and Axinyssa aplysinoides. All compounds possessed the spiro-axane sesquiterpene core and all were substituted at C-2 with nitrogen containing functionality. The stereochemistry of one known compound has been revised to (2R,5R,10S)-2-formamido-6-axene (3). It exhibited mild selective solid tumor and mild antibacterial activity and was found from Axinyssa. A second known substance whose stereochemistry has also been revised, (2R,5R,10S)-2-isothiocyanato-6-axene (4) plus its undescribed diastereomer (5) were isolated from Amorphinopsis. Both sponges were the source of two new N-phenethyl-2-formamido-6-axene diastereomeric compounds 6 and 7. No solid tumor or antibacterial activity was found for 4-7.     

Synthesis and characterization of n=5, 6 members of the La4Srn−4TinO3n+2 series with layered structure based upon perovskite

Layered compounds have been synthesized and structurally characterized for the n=5 and 6 members of the perovskite-related family La₄Sr_n−4Ti_nO_3n+2 by combining X-ray diffraction and transmission electron microscopy. Their structure can be regarded as comprising [(La,Sr)₅Ti₅O₁₇] and [(La,Sr)₆Ti₆O₂₀] perovskite blocks joined by crystallographic shears along the a-axis, with consecutive blocks shifted by 1/2 [100]_p. The n=5 member is similar to the previously reported n=5 member of other A_nB_nO_3n+2-related series. The n=6 member, which has only been briefly reported in other systems previously, is also a well-behaved member of this A_nB_nO_3n+2 series.     

Application of N,3-diaryl-3-oxo-propanethioamide in synthesis: an efficient and mild domino approach to highly substituted fused chromenones

A convenient and rapid synthesis of hitherto unknown 3-aroyl-4-aryl-2-phenylamino-4H-benzo[g]chromene-5,10-diones in high yield from β-aroyl-thioacetanilide, aromatic aldehyde, and 2-hydroxy-1,4-naphthoquinone via InCl₃ catalyzed one-pot three-component tandem Knoevenagel condensation–Michael addition–intramolecular cyclization–elimination reaction sequence is disclosed for the first time. This domino protocol has been used to obtain highly substituted pyrano[3,2-c]chromen-5(4H)-ones and 7,7-dimethyl-7,8-dihydro-4H-chromen-5(6H)-ones from N,3-diaryl-3-oxo-propanethioamide, aromatic aldehyde, and 4-hydroxycoumarine or dimedone under mild reaction conditions. A plausible reaction mechanism is proposed. The 4H-pyrano[3,2-c]chromen-5-one and 7,7-dimethyl-7,8-dihydro-4H-chromen-5(6H)-one derivatives possessing 3-(2-chlorobenzoyl)-2-phenylamino-substituents further cyclized under basic conditions to yield penta-cyclic 7,13-diaryl-5,14-dioxa-13-aza-benzo[a]naphthacen-6,8(7H,13H)-dione and tetra-cyclic 6,12-diaryl-3,3-dimethyl-3,4-dihydro-2H-chromeno[2,3-b]quinolin-1,11(6H,12H)-dione, respectively.     

Polyhydroxylated macrolide isolated from the endophytic fungus Pestalotiopsis mangiferae

A new polyhydroxylated macrolide, named mangiferaelactone (1) was isolated from a solid culture of the endophytic fungus Pestalotiopsis manguiferae, together with ten known compounds [(6S,1′S)-LL-P880α; (6S,1′S,2′R)-LL-P880β; (1′S,2′R)-LL-880γ; (1′R)-dehydropestalotin; (−)-5-carboxylmellein; (−)-5-methylmellein; (−)-5-hydroxylmethylmellein; arabenoic acid; 5,6-dihydro-4-methoxy-2H-pyran-2-one; and the (−)-2-hexylidene-3-methylsuccinic acid]. P. manguiferae was isolated from Hyptis dilatata, a small shrub common in the central region of Panama. The structure of compound 1 was elucidated by a combination of spectroscopic methods (IR, MS, optical rotation, 1D and 2D NMR spectroscopy). The absolute configuration of 1 was established as 4R,7R,8R,9S by application of vibrational circular dichroism (VCD). Compound 1 showed a minimum inhibitory concentration (MIC) of 1.6863 mg/mL against Listeria monocytogenes, and 0.5529 mg/mL against Bacillus cereus. No activity was observed for compound 1 against Plasmodium falciparum or Trypanosoma cruzi; likewise, no cytotoxic activity was observed against A2058 and H522-T1 cells.     

Hupermine A,a novel C16N2-type Lycopodium alkaloid from Huperzia phlegmaria

A novel C₁₆N₂-type Lycopodium alkaloid consisting of a quinolizidine with a 6-dimethylaminohexyl side chain, hupermine A (1), was isolated from the club moss of Huperzia phlegmaria, and the structure and relative stereochemistry were elucidated on the basis of spectroscopic data.     

Synthesis, characterization and crystal structures of cyclometallated palladium (II) compounds containing difunctional ligands with [P,P], [As,As], [N,N], [P,As], [P,N] and [P,O] donor atoms

Treatment of the chloro-bridged dinuclear complex [Pd{3,4-(MeO)₂C₆H₂C(H)N(Cy)-C6,N}(μ-Cl)]₂ (1) with homobidentate [P,P], [As,As], [N,N], and heterobidentate [P,As], [P,N] ligands in a 1:1 molar ratio gave the dinuclear complexes [{Pd[3,4-(MeO)₂C₆H₂C(H)N(Cy)-C6,N](Cl)}₂{μ-L}] (L = Ph₂PC₄H₆(NH)CH₂PPh₂ (2); Ph₂As(CH₂)₂AsPh₂ (3); 1,3-(NH₂CH₂)₂C₆H₄ (4); Ph₂P(CH₂)₂AsPh₂ (5); Ph₂P(CH₂)₂NH₂ (6)), with the bidentate ligands bridging the two cyclometallated fragments.The reaction with the homobidentate ligands in a 1:2 molar ratio in the presence of NaClO₄ afforded the mononuclear compounds [[Pd{3,4-(MeO)₂C₆H₂C(H)N(Cy)-C6,N}{L-P,P}][ClO₄] (L = Ph₂PC₄H₆(NH)CH₂PPh₂ (7); (o-Tol)₂P(CH₂)₂P(o-Tol)₂ (8)), [Pd{3,4-(MeO)₂C₆H₂C(H)N(Cy)-C6,N}{Ph₂As(CH₂)₂AsPh₂-As,As}][ClO₄] (9) and [Pd{3,4-(MeO)₂C₆H₂C(H)N(Cy)-C6,N}{L-N,N}][ClO₄] (L = NH₂(CH₂)₃NH₂ (10); NH₂(C₆H₈)CH₂(C₆H₈)NH₂ (11); 1,3-(NH₂CH₂)₂C₆H₄ (12); 1,3-(NH₂)₂C₅H₃N (13); NH₂(C₆H₄)O(C₆H₄)NH₂ (14); NMe₂(CH₂)₂NMe₂ (15)), in which the chloro ligands are absent and the bidentate ligands are chelated to the palladium atom.Reaction of 1 with Ph₂P(CH₂)₂AsPh₂ in 1:2 molar ratio in acetone in the presence of NH₄PF₆ afforded the analogous mononuclear compound [Pd{3,4-(MeO)₂C₆H₂C(H)N(Cy)-C6,N}{Ph₂P(CH₂)₂AsPh₂-P,As}][PF₆] (16); whereas reaction with Ph₂P(CH₂)₃NH₂ gave [Pd{3,4-(MeO)₂C₆H₂C(H)N(Cy)-C6,N}{Ph₂P(CH₂)₃N(CMe₂)-P,N}][PF₆] (17), derived from intermolecular condensation between the aminophosphine and acetone. Condensation of the NH₂ group was precluded by change of solvent, using dichloromethane.Iminophoshines also reacted with 1 in 1:2 molar ratio in acetone to give a new series of mononuclear cyclometallated complexes: [Pd{3,4-(MeO)₂C₆H₂C(H)N(Cy)-C6,N}{L-P,N}][ClO₄] (L = Ph₂PC₆H₄C(H)NCy (20); Ph₂PC₆H₄C(H)NC(CH₃)₃ (21); Ph₂PC₆H₄C(H)NNMe₂ (22); Ph₂PC₆H₄C(H)NNHMe (23); Ph₂PC₆H₄C(H)NNHPh (24)). Analogous complexes with a stable P,O-chelate were obtained using bidentate [P,O] donor ligands: [Pd{3,4-(MeO)₂C₆H₂C(H)N(Cy)-C6,N}{L-P,O}][Cl] (L = 2-(Ph₂P)C₆H₄CHO (25); Ph₂PN(Me)C(O)Me (26)).The crystal structures of compounds 1, 5, 15, 16, 18, 20 have been determined by X-ray crystallography.     

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.     

Cytotoxic cembranoids from the Red Sea soft coral, Sarcophyton auritum

Chemical investigation of the Red Sea soft coral Sarcophyton auritum led to the isolation and structure elucidation of two new diterpene cembranoids; 2-epi-sarcophine (2) and (1R,2E,4S,6E,8R,11R,12R)-2,6-cembradiene-4,8,11,12-tetrol (4), as well as two known diterpene cembranoids, reported for the first time from this species, namely sarcophine (1) and (+)-7α,8β-dihydroxydeepoxysarcophine (3). Structure elucidation was achieved using spectroscopic techniques, including 1D and 2D NMR and HRMS. The isolated cembranoids were found to display high cytotoxicity against HepG2 (liver cancer cell line) and MCF-7 (breast cancer cell line).     

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.     

Synthesis and characterization of new Rh complexes bearing CO, PPh3 and chelating P,O- or Se,Se-ligands: Application to hydroformylation of styrene

The complexes [Rh(CO)(PPh₃){Ph₂PNP(O)Ph₂-P,O}] (3), [Rh(CO)₂{Ph₂P(Se)NP(Se)Ph₂-Se,Se′}] (5), and [Rh(CO)(PPh₃){Ph₂P(Se)NP(Se)Ph₂-Se,Se′}] (6), were synthesised by stepwise reactions of CO and PPh₃ with [Rh(cod){Ph₂PNP(O)Ph₂-P,O}] (2) and [Rh(cod){Ph₂P(Se)NP(Se)Ph₂-Se,Se′}] (4), respectively. The complexes 3, 5 and 6 have been studied by IR, as well as ¹H and ³¹P NMR spectroscopy. The ν(CO) bands of complexes 3 and 6 appear at approximately 1960 cm⁻¹, indicating high electron density at the Rh^I centre. The structure of complexes 3 and 6 has been determined by X-ray crystallography, and the ³¹P NMR chemical shifts have been resolved via low temperature NMR experiments. Both complexes exhibit square planar geometry around the metal centre, with the five-membered ring of complex 3 being almost planar, and the six-membered ring of complex 6 adopting a slightly distorted boat conformation. The C-O bond of the carbonyl ligand is relatively weak in both complexes, due to strong π-back donation from the electron rich Rh^I centre. The catalytic activity of the complexes 2, 3 and 6 in the hydroformylation of styrene has been investigated. Complexes 2 and 3 showed satisfactory catalytic properties, whereas complex 6 had effectively no catalytic activity.     

Biotransformation of (+)-(1R,2S)-fenchol by the larvae of common cutworm (Spodoptera litura)

Biotransformation of (+)-(1R,2S)-fenchol by the larvae of Spodoptera litura was carried out. Substrate was converted to three new terpenoids, (+)-(1R,2S)-10-hydroxyfenchol, (+)-(1R,2R,3S)-8-hydroxyfenchol and (−)-(1S,2S,6S)-6-exo-hydroxyfenchol, and one known terpenoid, (−)-(1R,2R,3R)-9-hydroxyfenchol. These structures were established by NMR, IR, specific rotation and mass spectral studies.     

A xanthone and a polyketide derivative from the leaves of Cassia obtusifolia (Leguminosae)

A new xanthone, 1,8-dihydroxy-3-methoxy-6-methylxantone and a new polyketide derivative, (4R^∗,5S^∗,6E,8Z)-ethyl-4-((E)-but-1-enyl)-5-hydroxypentdeca-6,8-dienoate, together with 20 known secondary metabolites, including 2 steroids, 4 xanthones, 10 anthraquinones, 2 triterpenoids, 1 fatty ester, and (E)-eicos-14-enoic acid, were isolated from the leaves of Cassia obtusifolia. To the best of our knowledge, the last compound was isolated from a natural source for the first time. The structures of all the compounds were elucidated on the basis of 1D and 2D NMR experiments. Some of the compounds were tested against Salmonella typhi, Staphylococcus aureus, Candida albicans ATCC 9002, and Candida tropicalis, they did not show any activity.     

Crystal growth and structural investigation of A2BReO6 (A=Sr, Ba; B=Li, Na)

Single crystals of the double perovskite rhenates A₂BReO₆ (A=Sr, Ba; B=Li, Na) were grown out of molten hydroxide fluxes. Single crystals of orange/yellow Ba₂LiReO₆, Ba₂NaReO₆ and Sr₂LiReO₆ were solved in the cubic, Fm-3m space group with a=8.1214(11) Å, 8.2975(3) Å, and 7.9071(15) Å, respectively, while Sr₂NaReO₆ was determined to be monoclinic P2₁/n with a=5.6737(6) Å, b=5.7988(6) Å, c=8.0431(8) Å, and β=90.02(6) °. The cubic structure consists of a rock salt lattice of corner-shared ReO₆ and MO₆ (M=Li, Na) octahedra which, in the monoclinic structure, are both tilted and rotated. A discrepancy exists between the symmetry of Sr₂LiReO₆ indicated by the single-crystal refinement of flux-grown crystals (cubic, Fm-3m) and the symmetry indicated by the powder diffraction data collected on polycrystalline samples prepared by the ceramic method (tetragonal, I4/m). It is possible that the cubic crystals are a kinetic product that forms in small quantities at low temperatures, while the powder represents the more stable polymorph that forms at higher reaction temperature.     

Stereoselective total synthesis of the (Z)-isomer of a novel phytotoxic nonenolide from Phomopsis sp. HCCB03520 and its C-6 epimer

The (Z)-isomer of a phytotoxic nonenolide, (6S,7R,9R)-6,7-dihydroxy-9-propylnon-4-eno-9-lactone isolated from Phomopsis sp. HCCB03520 and its C-6 epimer have been synthesized through a common route starting from butyraldehyde. The synthesis involves enantioselective Maruoka allylation, Sharpless asymmetric epoxidation and intramolecular ring closing metathesis as the important steps.     

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.     

Isolation of secondary metabolites from Hortia oreadica (Rutaceae) leaves through high-speed counter-current chromatography

High-speed counter-current chromatography (HSCCC) with a two-phase solvent system (hexane–ethanol–acetonitrile–water 10:8:1:1, v/v) was applied to examine the leaves of Hortia oreadica, which afforded the known limonoid guyanin (1), the alkaloids rutaecarpin (2) and dictamnine (6), the dihydrocinnamic acid derivatives methyl 5,7-dimethoxy-2,2-dimethyl-2H-1-benzopyran-6-propanoate (3), 5,8-dimethoxy-2,2-dimethyl-2H-1-benzopyran-6-propanoic acid (4), together with the new E-3,4-dimethoxy-α(3-hydroxy-4-carbomethoxyphenyl)cinnamic acid (5). The recovery of compounds 1–6 was determined by comparison with LC-atmospheric pressure chemical ionization MS/MS data: 66.2%, 93.1%, 102.5%, 101.2%, 99.0% and 84.9%, respectively. Compound 3 showed IC₅₀ of 23.6 μM against Plasmodium falciparum and 15.6 μM against Trypanosoma brucei rhodesienses and was not toxic to KB cells (IC₅₀ > 100 μM).     

Isolation of naturally occurring dactylomelane metabolites as Laurencia constituents

Dactylomelol 1, initially isolated from molluscs of the genus Aplysia, was the first example of a monocarbocyclic diterpene skeleton with a C-6-C-11 cyclisation. This paper reports on the identification and structural elucidation of six new diterpenes, compounds 4-9, isolated from specimens of Laurencia sp., together with dactylomelol, all with this particular carbon backbone that we named dactylomelane. This result is the first to confirm a red alga as the biogenetic origin of this class of compounds.     

Identification of novel substituted fused aromatic compounds, meshimakobnol A and B, from natural Phellinus linteus fruit body

Novel 1H,6H-pyranyl[4,3-c][2]benzopyrane-1,6-diones, meshimakobnol A and B, were isolated from natural Phellinus linteus fruit body. The structure elucidation of these fused aromatic compounds was achieved by a spectroscopic method including the measurement of FG-HMBC with various delay times.     

Selective functionalization at the small rim of calix[6]arene. Synthesis of novel non-symmetrical N3, N4 and N3ArO biomimetic ligands

Eight novel calix[6]arene-based biomimetic ligands for transition metal ions have been synthesized. They display a non-symmetrical N₃, N₄ or N₃ArO binding core that mimics enzyme active sites presenting histidine and tyrosine residues. The key step for their synthesis is the mono-alkylation at the small rim of the C_3v symmetrical trimethyl ether derivative of tBu-calix[6]arene with N-Boc-2-chloroethylamine to yield a novel calix[6]arene synthon. Its combined O-alkylation with a chloromethyl aromatic amine and N-deprotection or alkylation or reductive alkylation with a salicylaldehyde derivative yielded the calix[6]arene-based ligands with mixed N/O donors.