Two new 3D (3,8)-connected metal-organic frameworks based on zinc-triazole secondary building units and benzenetricarboxylate linkers

Two new zinc-triazole-carboxylate frameworks constructed from secondary building units (SBUs), [Zn₅(trz)₄(btc)₂(DMF)₂(H₂O)₂]·2H₂O·DMF (1) and [Zn₄(trz)₃(btc)₂(CH₃CN)(H₂O)]·5H₂O·(Bu₄N) (2), [Htrz = 1,2,4-triazole, H₃btc = 1,2,4-benzenetricarboxylate, Bu₄N = tetrabutylammonium], have been synthesized by solvothermal reactions and characterized by single-crystal X-ray diffraction analyses, X-ray power diffraction, elemental analyses, infrared spectra and thermogravimetric analyses. Both compounds 1 and 2 exhibit 3D (3,8)-connected tfz-d nets with {4³}₂{4⁶.6¹⁸.8⁴} topology symbol built from rod-shaped {[Zn₅(trz)₄]⁶⁺}_n SBUs (1) and {[Zn₄(trz)₃]⁵⁺}_n SBUs (2). In two compounds, rodlike units are connected by btc ligands via different modes. Additionally, solid state fluorescent emission spectra of two compounds show fluorescent properties at room temperature.     

Limonoids from the seeds of a Godavari mangrove, Xylocarpus moluccensis

Ten limonoids, named godavarins A-J (1-7, 9-11), were isolated from seeds of an Indian mangrove (Xylocarpus moluccensis) collected in the mangrove wetlands of Godavari estuary, Andhra Pradesh. Eight known limonoids, viz. xyloccensins L (8), P (12), Q (13), mexicanolide (14), 6-deoxy-3-detigloyl-swietenine acetate (15), fissinolide (16), methyl 3β-acetoxy-1-oxomeliaca-8(30),14-dienoate (17), and methyl 3β-acetoxy-1-oxomeliaca-8(9),14-dienoate (18), were also obtained. The structures of these compounds were established on the basis of spectroscopic data or comparison with data in the literature (known compounds). The stereostructure of godavarin D was confirmed by means of single-crystal X-ray analysis. Godavarins A-C are the first mexicanolide derivatives with a C₇-C₂₈ ester-linked δ-lactone ring, while godavarins D-G are further additions to the small group of limonoids with a C₁-C₂₉ oxygen bridge. Godavarin H is a phragmalin with five acetoxy groups. Two limonoids, mexicanolide and fissinolide, were found to exhibit marked antifeedant activity against the third-instar larvae of Brontispa longissima (Gestro) at a concentration of 0.5 mg/mL. The most potent compound was mexicanolide. It also showed moderate insecticidal activity.     

Preparation of cobalt sandwich diphosphine ligand [(η-C5H4Pr)Co(η-C4(PPh2)2Ph2)] and its chelated palladium complex: Application of diphosphine ligand in the preparation of mono-substituted ferrocenylarenes

The reaction of (η⁵-C₅H₄ⁱPr)Co(PPh₃)₂ with PhCCPPh₂ furnished two isomeric cyclobutadiene-substituted Cp′CoCb diphosphines, [(η⁵-C₅H₄ⁱPr)Co(η⁴-1,2-(PPh₂)₂C₄Ph₂)] (5-cis) and [(η⁵-C₅H₄ⁱPr)Co(η⁴-1,3-(PPh₂)₂C₄Ph₂)] (5-trans). Further reaction of 5-cis with one molar equivalent of Pd(COD)Cl₂ gave palladium complex [(η⁵-C₅H₄ⁱPr)Co(η⁴-1,2-(PPh₂)₂C₄Ph₂)-PdCl₂] (6) in good yield. Both of the molecular structures of 5-cis and 6 were determined by single-crystal X-ray diffraction methods. Unexpectedly, the palladium complex 6 was found to be more efficient than the combination of the commonly used Buchwald’s ligand, biphenyl-2-yl-di-tert-butyl-phosphane, with Pd(OAc)₂ as the catalytic precursor in the Suzuki-Miyaura reaction between ferroceneboronic acid and 4-bromoaldehyde. The X-ray structural analysis and DFT study of several palladium complexes containing sandwich-type diphosphine chelating ligands revealed that the variations in bite angles are much larger than those in bite distances. The more energetically favorable conformation in the Pd(II) complexes is the one with bite angle close to 90°.     

Assembly of coordination networks: Role of the different M(II)-cysteate chain in structural diversification

In this paper, we have presented the synthesis and crystal structures of five coordination polymers, namely, {[Ni₂(cysteate)₂(bpy)₂(H₂O)₂]·3H₂O}_n (1), {[Cu₂(cysteate)₂(bpy)₂(H₂O)₂]·4H₂O}_n (2), {[Mn₂(cysteate)₂(bpy)(H₂O)₄](bpy)·H₂O}_n (3), {[Zn₂(cysteate)₂(bpy)(H₂O)₄](bpy)·H₂O}_n (4), {[Cd(cysteate)(bpy)(H₂O)]·4H₂O}_n (5), using homochiral l-cysteate and 4,4′-bipyridine (bpy) as mixed ligands, reacted with Ni(II), Cu(II), Mn(II), Zn(II) and Cd(II) ions, respectively. When different metal centers being used, l-cysteate gave rise to three different architectures based on coordination polymeric chains: (1) a helical chain, which is further connected by bpy pillars to generate a racemic twofold 3D (4².8⁴)-lvt net in 1 and 2; (2) a zigzag chain, which is further linked by bpy pillars into a homochiral 2D brick-wall structure in 3 and 4; (3) a zigzag chain, which is further linked by bpy pillars into a homochiral 2D 4⁴ grid network in 5. These results indicate that the metal-directed M(II)-cysteate chain has an important effect on the structural diversification of such complexes.     

Selective antagonists of mouse trace amine-associated receptor 1 (mTAAR1): discovery of EPPTB (RO5212773)

High throughput screening of the Roche compound library identified benzanilides such as 1 and 2 as antagonists of TAAR1. Optimisation of this hit series led to the first selective TAAR1 antagonist (N-(3-Ethoxy-phenyl)-4-pyrrolidin-1-yl-3-trifluoromethyl-benzamide EPPTB (RO5212773, 9f) having IC₅₀ of 28 nM at mouse TAAR1.     

Synthesis and antimicrobial activity of some new N-glycosides of 2-thioxo-4-thiazolidinone derivatives

5-Arylidene-2-thioxo-4-thiazolidinones 3a-f react with each of 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl and α-d-galactopyranosyl bromides 4a,b in acetone in the presence of aqueous potassium hydroxide at room temperature to afford N-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl) or N-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl) 2-thioxo-4-thiazolidinone derivatives 5a-f. Similarly, the reaction of 5-cycloalkylidene-2-thioxo-4-thiazolidinones 7a,b with 4a gave the corresponding N-glucosides 8a,b. Also, 5-pyrazolidene rhodanines 10a-e react with 4a to afford the new N-glucosides 11a-e. Treatment of compounds 15 and 16 with 4a in the presence of few drops of triethylamine or in KOH solution accomplished the mono- and bis-nucleosides 17 and 18, respectively. Some selected products were tested for their antimicrobial activities.     

Iridoid glycosides from Gardeniae Fructus for treatment of ankle sprain

The iridoid glycosides, genipin 1-O-β-d-isomaltoside (1) and genipin 1,10-di-O-β-d-glucopyranoside (2), together with six known iridoid glycosides, genipin 1-O-β-d-gentiobioside (3), geniposide (4), scandoside methyl ester (5), deacetylasperulosidic acid methyl ester (6), 6-O-methyldeacetylasperulosidic acid methyl ester (7), and gardenoside (8) were isolated from an EtOH extract of Gardeniae Fructus. The structures and relative stereochemistries of the metabolites were elucidated on the basis of 1D- and 2D-NMR spectroscopic techniques, high-resolution mass spectrometry, and chemical evidence. Geniposide (4), one of the main compounds of Gardeniae Fructus, was tested for treatment of ankle sprain using an ankle sprain model in rats. From the second to fifth day, the geniposide (4) (100 mg/ml) treated group exhibited significant differences (p < 0.01) with ∼21-34% reduction in swelling ratio compared with those of the vehicle treated control group. This indicated the potential effect of geniposide (4) for the treatment of disorders such as ankle sprain.     

Bis(pyrazolyl) palladium(II), platinum(II) and gold(III) complexes: Syntheses, molecular structures and substitution reactions with l-cysteine

A series of pyrazolyl palladium(II), platinum(II) and gold(III) complexes, [PdCl₂(3,5-R₂bpza)] {R = H (1), R = Me (2), bpza = bis-pyrazolyl acetic acid}, [PtCl₂(3,5-R₂bpza)] {R = H (3a), R = Me (4)}, [AuCl₂(3,5-R₂bpza)]Cl {R = H (5a), R = Me (6a)} and [PdCl₂(3,5-R₂bpzate)] {R = Me (7)} have been synthesised and structurally characterised. Single crystal X-ray crystallography showed that the pyrazolyl ligands exhibit N^N-coordination with the metals. Anticancer activities of six complexes 1-6a were investigated against CHO cells and were found to have low activities. Substitution reactions of selected complexes 1, 2, 3a and 5a with l-cysteine show that the low anticancer activities compounds and that the rate of substitution with sulfur-containing compounds is not the cause of the low anticancer activities.     

Exploration of antimicrobial and antioxidant potential of newly synthesized 2,3-disubstituted quinazoline-4(3H)-ones

A series of 2-(chloromethyl)-3-(4-methyl-6-oxo-5-[(E)-phenyldiazenyl]-2-thioxo-5,6-dihydropyrimidine-1(2H)-yl)quinazoline-4(3H)-ones 9a-j was synthesized by treating 2-(chloroacetyl)amino benzoic acid with 3-amino-6-methyl-5-[(E)-phenyldiazenyl]-2-thioxo-2,5-dihydropyrimidine-4(3H)-one 8a-j and was screened for in vitro antibacterial activities against a representative panel of Gram-positive and Gram-negative bacteria. The compounds were synthesized in excellent yields and the structures were corroborated on the basis of IR, ¹H NMR, Mass and elemental analysis data. All the synthesized compounds elicited the potent inhibitory action against all the tested bacterial stains. Furthermore, in order to explore the antioxidant potential of newly synthesized compounds, the free radical scavenging activity measurement were performed by the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) assay method. It is revealed from the antioxidant screening results that the compounds 9c and f manifested profound antioxidant potential.     

Allelopathy is involved in the formation of pure colonies of the fern Gleichenia japonica

The fern Gleichenia japonica is one of the most widely distributed fern and occurs throughout East to South Asia. The species often dominates plant communities by forming large monospecific colonies. However, the potential mechanism for this domination has not yet been described. The objective of this study was to test the hypothesis that allelochemicals are involved in the formation of G. japonica colonies. An aqueous methanol extract of G. japonica inhibited the growth of seedlings of garden cress (Lepidium sativum), lettuce (Lactuca sativa), ryegrass (Lolium multiflorum) and timothy (Phleum pratense). Increasing extract concentration increased the inhibition. These results suggest that G. japonica contain allelopathic substances. The extract was then purified by several chromatographies with monitoring the inhibitory activity and two growth inhibitory substances causing the allelopathic effect were isolated. The chemical structures of the two substances were determined by spectral data to be a novel compound 3-O-β-allopyranosyl-13-O-β-fucopyranosyl-3β-hydroxymanool (1) and 18-O-α-l-rhamnopyranosyl-(1→2)-β-d-glucopyranosyl-13-epitorreferol (2). These compounds inhibited the shoot and root growth of garden cress, lettuce, alfalfa (Medicago sativa), timothy, ryegrass and barnyardgrass (Echinochloa crus-galli) at concentrations greater than 0.1–1.0 mM. The concentrations required for 50% growth inhibition of root and shoot growth of these test plants ranged from 0.72 to 3.49 mM and 0.79 to 3.51 mM for compounds 1 and 2, respectively. Concentration of compounds 1 and 2 in soil under the pure colony of G. japonica was 4.9 and 5.7 mM, respectively, indicating concentrations over those required for 50% growth inhibition are potentially available under monocultural stands of these ferns. Therefore, these compounds may contribute to the allelopathic effects caused by presence of G. japonica and may thus contribute to the establishment of monocultural stands by this fern.     

Synthesis of new N-substituted 3,4,5-trihydroxypiperidin-2-ones from d-ribono-1,4-lactone

d-Ribono-1,4-lactone was treated with ethylamine in DMF to afford N-ethyl-d-ribonamide 8a in quantitative yield. Using this reaction procedure, N-butyl, N-hexyl, N-dodecyl, N-benzyl, N-(3-methyl-pyridinyl)-, N-(2-hydroxy-ethyl)-, and N-(2-cyano-ethyl)-d-ribonamides 8b-h were obtained in quantitative yield. Bromination of the amides 8a-e with acetyl bromide in dioxane followed by acetylation gave 2,3,4-tri-O-acetyl-5-bromo-5-deoxy-N-ethyl, N-butyl, N-hexyl, N-dodecyl, and N-benzyl-d-ribonamides 9a-e in 40-54% yields. To obtain 2,3,4-tri-O-acetyl-5-bromo-5-deoxy-N-(3-methyl-pyridinyl)-, N-(2-hydroxy-ethyl)-, and N-(2-cyano-ethyl)-9f-h, the bromination is necessary before the amidation reaction. Treatment of the bromoamides 9a-h with NaH in DMF followed by methanolysis affords N-alkyl-d-ribono-1,5-lactams 12a-h in quantitative yield.     

New pyridyl modified phosphines: Synthesis and late transition-metal coordination studies

Using a phosphorus based Mannich condensation reaction the new pyridylphosphines {5-Ph₂PCH₂N(H)}C₅H₃(2-Cl)N (1-Cl) and {2-Ph₂PCH₂N(H)}C₅H₃(5-Br)N (1-Br) have been synthesised in good yields (60% and 88%, respectively) from Ph₂PCH₂OH and the appropriate aminopyridine. The ligands 1-Cl and 1-Br display variable coordination modes depending on the choice of late transition-metal complex used. Hence P-monodentate coordination has been observed for the mononuclear complexes AuCl(1-Cl) (2), AuCl(1-Br) (3), RuCl₂(p-cymene)(1-Cl) (4), RuCl₂(p-cymene)(1-Br) (5), RhCl₂(Cp^∗)(1-Cl) (6), RhCl₂(Cp^∗)(1-Br) (7), IrCl₂(Cp^∗)(1-Cl) (8), IrCl₂(Cp^∗)(1′-Cl) (8′), IrCl₂(Cp^∗)(1-Br) (9), cis-/trans-PdCl₂(1-Cl)₂ (10), cis-/trans-PdCl₂(1-Br)₂ (11), cis-PtCl₂(1-Cl)₂ (12) and cis-PtCl₂(1-Br)₂ (13). Reaction of Pd(Me)Cl(cod) (cod = cycloocta-1,5-diene) with either 1 equiv. of 1-Br or the known pyridylphosphines 1′-Cl, 1-OH or 1-H gave the P/N-chelate complexes Pd(Me)Cl(1-Br-1-H) (14)-(17). All new compounds have been fully characterised by spectroscopic and analytical methods. Furthermore the structures of 4, 5, 10 and 16 · (CH₃)₂SO have been elucidated by single crystal X-ray crystallography. A crystal structure of the dinuclear metallocycle trans,trans-[PdCl₂{μ-P/N-{Ph₂PCH₂N(H)}C₅H₄N}]₂ · CHCl₃, 18 · CHCl₃, has also been determined. Here 1-H bridges, using both P and pyridyl N donors, two dichloropalladium centres affording a 12-membered ring with the PdCl₂ units adopting a head-to-tail arrangement.     

Isolation and structure elucidation of 5′-O-β-d-glucopyranosyl-dihydroascorbigen from Cardamine diphylla rhizome

From the methanol extract of Cardamine diphylla rhizome, 5′-O-β-d-glucopyranosyl-dihydroascorbigen (1) and 6-hydroxyindole-3-carboxylic acid 6-O-β-d-glucopyranoside (2) were isolated. The structures of the compounds were elucidated using spectroscopic methods. This is the second report on the presence of a glucosylated indole ascorbigen in plants.     

Effect of metal coordination and intra-molecular H-bond on the acidity of phenolic proton in a set of structurally characterized octahedral Ni(II) complexes of l-histidine derivative

Four different mononuclear octahedral Ni(II) complexes with protonated and deprotonated form of the same ligand have been synthesized by controlling reaction conditions and structurally characterized. The complexes are [Ni(HL^l-his)(benzoate)(MeOH)] (1), [Ni(HL^l-his)(SCN)(MeOH)] (2), [Ni(HL^l-his)₂] (3) and [Ni(L^l-his)(imidazole)₂] (4) where H₂L^l-his is (S)-2-(2-hydroxybenzylamino)-3-(1H-imidazol-4-yl)-propionic acid. The ligand behaves as a monobasic tetradentate ligand in 1 and 2, monobasic tridentate ligand in 3 and dibasic tetradentate ligand in 4. Ni(II) coordinated phenolic proton of the ligand in the complexes 1-2 shows strong intra-molecular H-bonding with benzoate in 1 and lattice water in 2, whereas 3 shows intermolecular H-bonding between uncoordinated phenols with neighbouring carboxylate. The pH titration of the complexes revealed that metal coordination and H-bond in complexes 1 and 2 considerably lowers the acidity of ligand phenol (pK_a 6.8 and 7.0 respectively) compared to phenol (pK_a 10). The complex 4 does not show any proton loss due to the absence of phenolic proton. All the complexes show extensive H-bonded network in the crystals including narrow (7.8 × 5.2 Å) water filled one dimensional channel in 2.     

Stereoselective entry into the d-GalNAc series starting from the d-Gal one: a new access to N-acetyl-d-galactosamine and derivatives thereof

A new stereoselective preparation of N-aceyl-d-galactosamine (1b) starting from the known p-methoxyphenyl 3,4-O-isopropylidene-6-O-(1-methoxy-1-methylethyl)-β-d-galactopyranoside (10) is described using a simple strategy based on (a) epimerization at C-2 of 10 via oxidation-reduction to give the talo derivative 11, (b) amination with configurational inversion at C-2 of 11 via a S_N2-type reaction on its 2-imidazylate, (c) anomeric deprotection of the p-methoxyphenyl β-d-galactosamine glycoside 14, (d) complete deprotection. Applying the same protocol to 2,3:5,6:3′,4′-tri-O-isopropylidene-6′-O-(1-methoxy-1-methylethyl)-lactose dimethyl acetal (4), directly obtained through acetonation of lactose, the disaccharide β-d-GalNAcp-(1→4)-d-Glcp (1a) was obtained with complete stereoselectivity in good (40%) overall yield from lactose.     

Synthesis and antitumor activity of new d-seco and d-homo androstane derivatives

Starting from 3β-hydroxy-17-oxo-16,17-secoandrost-5-ene-16-nitrile (1), the new 16,17-secoandrostane derivatives 4-9 were synthesized. On the other hand, 3β-hydroxy-17-oxa-d-homoandrost-5-ene-16-one (10) yielded the new d-homo derivatives 12, 13 and 15. In vitro antiproliferative activity of selected compounds against three tumor cell lines (human breast adenocarcinoma ER+, MCF-7, human breast adenocarcinoma ER−, MDA-MB-231, prostate cancer AR−, PC-3, and normal fetal lung fibroblasts, MRC-5) was evaluated. Compounds 3 and 12 showed strong antiproliferative activity against PC-3 cells, the IC₅₀ values being 2 μM and 0.55 μM, respectively. Compounds 6 (10 μM) and 14 (9 μM) showed moderate activity against MDA-MB-231 cells. The synthesized compounds 1-3, 5-8, 10 and 12-15 were not toxic to normal fetal lung fibroblasts cells, MRC-5.     

Synthesis and biological properties of macrolactam analogs of the natural product macrolide (−)-A26771B

Promising synthetic derivatives of macrolactone natural product (−)-A26771B have been designed and synthesized both from semisynthesis and total synthesis. Further optimization led to the first synthesis of macrolactam analogs of (−)-A26771B with improved antibacterial activity and metabolic stability.     

Caffeoyl arbutin and related compounds from the buds of Vaccinium dunalianum

Dunalianosides A-I (1-9), esters of arbutin and related phenolic glucosides, were isolated from the buds of Vaccinium dunalianum Wight (Ericaceae) together with 20 known compounds, and their structures were established on the basis of 1- and 2D NMR spectroscopic evidence. Dunalianosides F-H were dimers of p-hydroxyphenyl 6-O-trans-caffeoyl-β-d-glucopyranoside (10). The latter was obtained in extraordinary high yield (22% of dry weight), and dunalianoside I (9) was found to be a conjugate of arbutin with an iridoid glucoside.     

Synthesis of monodeoxy and mono-O-methyl congeners of methyl β-d-mannopyranosyl-(1→2)-β-d-mannopyranoside for epitope mapping of anti-Candida albicans antibodies

A panel of six complementary monodeoxy and mono-O-methyl congeners of methyl β-d-mannopyranosyl-(1→2)-β-d-mannopyranoside (1) were synthesized by stereoselective glycosylation of monodeoxy and mono-O-methyl monosaccharide acceptors with a 2-O-acetyl-glucosyl trichloroacetimidate donor, followed by a two-step oxidation-reduction sequence at C-2′. The β-manno configuration of the final deprotected congeners 2-7 was confirmed by measurement of ¹J_C1,H1 heteronuclear and ³J_1′,2′ homonuclear coupling constants. These disaccharide derivatives will be used to map the epitope recognized by a protective anti-Candida albicans monoclonal antibody C3.1 (IgG3) and to determine its key polar contacts with the binding site.     

Novel and facile synthesis of furanodictines A and B based on transformation of 2-acetamido-2-deoxy-d-glucose into 3,6-anhydro hexofuranoses

A novel synthesis of furanodictines A [2-acetamido-3,6-anhydro-2-deoxy-5-O-isovaleryl-d-glucofuranose (1)] and B [2-acetamido-3,6-anhydro-2-deoxy-5-O-isovaleryl-d-mannofuranose (2)] is described starting from 2-acetamido-2-deoxy-d-glucose (GlcNAc). The synthetic protocol is based on deriving the epimeric bicyclic 3,6-anhydro sugars [2-acetamido-3,6-anhydro-2-deoxy-d-glucofuranose (4) and 2-acetamido-3,6-anhydro-2-deoxy-d-mannofuranose (5)] from GlcNAc. Reaction with borate upon heating led to a facile transformation of GlcNAc into the desired epimeric 3,6-anhydro sugars. The C5 hydroxyl group of the 3,6-anhydro compounds 4 and 5 was regioselectively esterified with the isovaleryl chloride to complete the synthesis of furanodictines A and B, respectively. The targets 1 and 2 were synthesized in only two steps requiring no protection/deprotection.