Xanthones from Hypericum chinense

Six xanthones, 1,3,7-trihydroxy-2-(2-hydroxy-3-methyl-3-butenyl)-xanthone (1), 1,7-dihydroxy-2,3-[2'-(1-hydroxy-1-methylethyl)-dihydrofurano]-xanthone (2), 1,3,7-trihydroxy-5-methoxyxanthone (3), 1,7-dihydroxy-5,6-dimethoxyxanthone (4), 4,5-dihydroxy-2,3-dimethoxyxanthone (5), 1,3-dihydroxy-2,4-dimethoxyxanthone (6) and 21 known xanthones were isolated from the leaves and stems of Hypericum chinense. Their structures were established based on spectroscopic studies.     

Flavonoids from Iryanthera laevis

Trunk wood of Iryanthera laevis Markgr. (Myristicaceae) contains 2′,4′-dihydroxy- 4,6′dimethoxydihydrochalcone, three 2′-hydroxy-4′,5′-methylenedioxyflavans with differently substituted A-rings (7-OH-6,8-diMe; 7-OH-5,8-diMe; 5-OH-7-OMe-6,8-diMe) and 1-(2′-hydroxy-4′-methoxy-5′-methylphenyl)-3(2″-hydroxy-4″,5″-methylenedioxphenyl)- propane, as well as three additional known diarylpropanes.     

Syntheses of benzophenone-xanthone hybrid polyketides and their antibacterial activities

Muchimangins are benzophenone-xanthone hybrid polyketides produced by Securidaca longepedunculata. However, their biological activities have not been fully investigated, since they are minor constituents in this plant. To evaluate the possibility of muchimangins as antibacterial agent candidates, five muchimangin analogs were synthesized from 2,4,5-trimethoxydiphenyl methanol and the corresponding xanthones, by utilizing p-toluenesulfonic acid monohydrate for the Brønsted acid-catalysis. The antibacterial assays against Gram-positive bacteria, Staphylococcus aureus and Bacillus subtilis, and Gram-negative bacteria, Klebsiella pneumoniae and Escherichia coli, revealed that the muchimangin analogs (±)-1,3,6,8-tetrahydroxy-4-(phenyl-(2′,4′,5′-trimethoxyphenyl)methyl)-xanthone (1), (±)-1,3,6-trihydroxy-4-(phenyl-(2′,4′,5′-trimethoxyphenyl)methyl)-xanthone (2), and (±)-1,3-dihydroxy-4-(phenyl-(2′,4′,5′-trimethoxyphenyl)methyl)-xanthone (3) showed significant activities against S. aureus, with MIC values of 10.0, 10.0, and 25.0 μM, respectively. Analogs (±)-1 and (±)-2 also exhibited antibacterial activities against B. subtilis, with MIC values of 50.0 and 12.5 μM, respectively. Furthermore, (+)-3 enhanced the antibacterial activity against S. aureus, with a MIC value of 10 μM.     

Mononuclear and tetranuclear palladacycles with terdentate [C,N,N] and [C,N,O] Schiff base ligands. C-H versus C-Br activation reactions

Reaction of the Schiff base ligands 2-Br-4,5-(OCH₂O)C₆H₂C(H)NCH₂CH₂NMe₂ (a) and 4,5-(OCH₂CH₂)C₆H₃C(H)NCH₂CH₂NMe₂ (b) with Pd(OAc)₂ or K₂[PdCl₄] leads to the mononuclear cyclometallated compounds [Pd{2-Br-4,5-(OCH₂O)C₆HC(H)NCH₂CH₂NMe₂-C6,N,N}(OCOMe)] (1a) and [Pd{4,5-(OCH₂CH₂)C₆H₂C(H)NCH₂CH₂NMe₂-C6,N,N}(Cl)] (1b), derived from C-H activation at the C6 carbon. Treatment of a with Pd₂(dba)₃ gave [Pd{4-5-(OCH₂O)C₆H₂C(H)NCH₂CH₂NMe₂-C2,N,N}(Br)] (2a), via C-Br activation.The metathesis reaction of 1a with aqueous sodium chloride gave [Pd{2-Br-4,5-(OCH₂O)C₆HC(H)NCH₂CH₂NMe₂-C6,N,N}(Cl)] (3a), with exchange of the acetate group by a chloride ligand. Treatment of the cyclometallated monomers 1a-3a with PPh₃ in a 1:1 molar ratio yielded the mononuclear complexes [Pd{2-Br-4,5-(OCH₂O)C₆HC(H)NCH₂CH₂NMe₂-C6,N}(L)(PPh₃)] (L: OAc, 4a; Cl, 5a) and [Pd{4-5-(OCH₂O)C₆H₂C(H)NCH₂CH₂NMe₂-C2,N}(Br)(PPh₃)] (6a), with Pd-NMe₂ bond cleavage. However, treatment of a solution of 3a or 2a with silver trifluoromethanesulfonate, followed by reaction with PPh₃ in acetone yielded the cyclometallated complexes [Pd{2-Br-4,5-(OCH₂O)C₆HC(H)NCH₂CH₂NMe₂-C6,N,N}(PPh₃)][CF₃SO₃] (7a) and [Pd{4-5-(OCH₂O)C₆H₂C(H)NCH₂CH₂NMe₂-C2,N,N}(PPh₃)][CF₃SO₃] (8a), respectively, where the Pd-NMe₂ bond was retained.The reaction of the ligands 2-Br-4,5-(OCH₂O)C₆H₂C(H)N(2′-OH-5′-^tBuC₆H₃) (c) and 4,5-(OCH₂CH₂)C₆H₃C(H)N(2′-OH-5′-^tBuC₆H₃) (d) with Pd(OAc)₂ gave the tetranuclear complexes [Pd{2-Br-4,5-(OCH₂O)C₆HC(H)N(2′-O-5′-^tBuC₆H₃)-C6,N,O}]₄ (1c) and [Pd{4,5-(OCH₂CH₂)C₆H₂C(H)N(2′-O-5′-^tBuC₆H₃)-C6,N,O}]₄ (1d), respectively. Treatment of 1c with PPh₃ in 1:4 molar ratio, gave the mononuclear species [Pd{2-Br-4,5-(OCH₂O)C₆HC(H)N(2′-(O)-5′-^tBuC₆H₃)-C6,N,O}(PPh₃)] (2c) with opening of the polynuclear structure after P-O_bridging bond cleavage.The structure of compounds 2a, 1c and 1d has been determined by X-ray diffraction analysis.     

Discovery of pyrrolo[2,3-d]pyrimidin-4-ones as corticotropin-releasing factor 1 receptor antagonists with a carbonyl-based hydrogen bonding acceptor

A new class of pyrrolo[2,3-d]pyrimidin-4-one corticotropin-releasing factor 1 (CRF₁) receptor antagonists has been designed and synthesized. In general, reported CRF₁ receptor antagonists possess a sp²-nitrogen atom as hydrogen bonding acceptor (HBA) on their core scaffolds. We proposed to use a carbonyl group of pyrrolo[2,3-d]pyrimidin-4-one derivatives as a replacement for the sp²-nitrogen atom as HBA in classical CRF₁ receptor antagonists. As a result, several pyrrolo[2,3-d]pyrimidin-4-one derivatives showed CRF₁ receptor binding affinity with IC₅₀ values in the submicromolar range. Ex vivo ¹²⁵I-sauvagine binding studies showed that 2-(dipropylamino)-3,7-dimethyl-5-(2,4,6-trimethylphenyl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one (16b) (30 mg/kg, po) was able to penetrate into the brain and inhibit radioligand binding to CRF₁ receptors (frontal cortex, olfactory bulb, and pituitary) in mice. We identified pyrrolo[2,3-d]pyrimidin-4-one derivatives as the first CRF₁ antagonists with a carbonyl-based HBA.     

Synthesis and characterization of cobalamines with anionic and neutral phosphorous donor ligands

In dimethyl formamide as solvent aquacobalamine reacts with the triorganyl phosphites 3–7 to give the corresponding (diorganylphosphito-P)cobalamines, their new β-axial ligands [P(O)(OR)₂]⁻ (3a–7a) being formed by partial hydrolysis. In methanol, however, additional methanolysis normally leads to (dimethylphosphito-P)cobalamine with the axial ligand [P(O)-(OMe)₂]⁻ (2a). Exceptions are P(OCH₂CH₂NMe₂)₃ (4) giving a complex with the only partially methanolized chiral ligand [P(O)(OCH₂CH₂NMe₂)- (OMe)]⁻ (4b), too, and the bicyclic phosphite 5 which is also coordinated in the unchanged, nonhydrolyzed form. All complexes are characterized by elementary analysis, electrophoresis, UVVis and ¹H, ³¹P NMR spectra. The chirality of the cobalamine moiety causes diatropism of the two organyl groups in the prochiral ligands [P(O)(OR)₂]⁻ which is well seen in the NMR spectra of the complexes with the methyl and phenyl derivatives 2a and 6a, whereas the spectra with ligands 3a and (in part) 4a are not resolved well enough to distinguish the two forms. With the chiral ligand 4b two diastereomers are obtained in different yields; this asymmetric induction is indicated by the intensities of the respective signals in the NMR spectra.     

Vasodilatory actions of xanthones isolated from a Tibetan herb,Halenia elliptica

In this study, six major xanthones, isolated and identified from Halenia elliptica were investigated for their vasodilatory actions in isolated rat coronary artery. The xanthones, including 1-hydroxy-2,3,5-trimethoxy-xanthone (HM-1), 1-hydroxy-2,3,4,7-tetramethoxy-xanthone (HM-2), 1-hydroxy-2,3,4,5-tetramethoxy-xanthone (HM-3), 1,7-dihydroxy–2,3,4,5-tetramethoxy-xanthone (HM-4), 1,5-dihydroxy-2,3-dimethoxy-xanthone (HM-5) and 1,7-dihydroxy-2,3-dimethoxy-xanthone (HM-7) caused vasodilation in the coronary artery pre-contracted with 1 μM 5-hydroxytryptamine (5-HT), with EC₅₀ values ranging from 1.4±0.1 μM (HM-1) to 6.6±1.4 μM (HM-2). The EC₅₀ values of the other xanthones were between those of HM-1 and HM-2. Removal of endothelium of the coronary artery led to decreases in the vasorelaxant effects of HM-1, HM-7 but not HM-2, HM-3, HM-4 and HM-5. Our results showed that xanthones isolated from Halenia elliptica are vasoactive substances which exhibit either endothelium-dependent or endothelium-independent mechanisms in rat coronary artery. The potency and mechanism(s) of the vasorelaxant effects of these xanthones may be relevant to the structure–activity differences in the level and the position of the substituent groups with the primary xanthone structure.     

Vasodilatory actions of xanthones isolated from a Tibetan herb,Halenia elliptica

In this study, six major xanthones, isolated and identified from Halenia elliptica were investigated for their vasodilatory actions in isolated rat coronary artery. The xanthones, including 1-hydroxy-2,3,5-trimethoxy-xanthone (HM-1), 1-hydroxy-2,3,4,7-tetramethoxy-xanthone (HM-2), 1-hydroxy-2,3,4,5-tetramethoxy-xanthone (HM-3), 1,7-dihydroxy–2,3,4,5-tetramethoxy-xanthone (HM-4), 1,5-dihydroxy-2,3-dimethoxy-xanthone (HM-5) and 1,7-dihydroxy-2,3-dimethoxy-xanthone (HM-7) caused vasodilation in the coronary artery pre-contracted with 1 μM 5-hydroxytryptamine (5-HT), with EC₅₀ values ranging from 1.4±0.1 μM (HM-1) to 6.6±1.4 μM (HM-2). The EC₅₀ values of the other xanthones were between those of HM-1 and HM-2. Removal of endothelium of the coronary artery led to decreases in the vasorelaxant effects of HM-1, HM-7 but not HM-2, HM-3, HM-4 and HM-5. Our results showed that xanthones isolated from Halenia elliptica are vasoactive substances which exhibit either endothelium-dependent or endothelium-independent mechanisms in rat coronary artery. The potency and mechanism(s) of the vasorelaxant effects of these xanthones may be relevant to the structure–activity differences in the level and the position of the substituent groups with the primary xanthone structure.     

Triaryl (Z)-olefins suitable for radiolabeling with carbon-11 or fluorine-18 radionuclides for positron emission tomography imaging of cyclooxygenase-2 expression in pathological disease

A group of (Z)-1,1-diphenyl-2-(4-methylsulfonylphenyl)alk-1-enes were synthesized using methodologies that will allow incorporation of a [¹¹C]OCH₃ substituent at the para-position of the C-1 phenyl ring, a [¹¹C]SO₂CH₃ substituent at the para-position of the C-2 phenyl ring, a [¹⁸F]OCH₂CH₂F substituent at the para-position of the C-1 phenyl ring, and a [¹⁸F]CH₂CH₂F substituent at the C-2 position of the olefinic bond. The [¹¹C] and [¹⁸F] radiotracers are designed as potential radiopharmaceuticals to image cyclooxygenase-2 (COX-2) expression in any organ where COX-2 is upregulated. The COX-1/COX-2 inhibition data acquired suggest that compounds having a [¹¹C]OMe or [¹⁸F]OCH₂CH₂F substituent at the para-position of the C-1 phenyl ring may be more suitable for imaging COX-2 expression in view of their ability to exclusively inhibit the COX-2 isozyme.     

New cell wall glycopolymers of the representatives of the genus Kribbella

Each of the cell walls of four representatives of the genus Kribbella (order Actinomycetales; suborder Propionibacterineae; family Nocardioidaceae) contains a neutral polysaccharide and an acidic polysaccharide with unusual structures. Common to all four strains studied is a mannan with the following repeating unit: In the cell wall of the strain VKM Ac-2541, a teichulosonic acid was identified with a monosaccharide component that has not hitherto been found in Gram-positive bacteria, viz., pseudaminic acid, and an unusual linkage type in the polymeric chain,

Full-size image (1K)

where R = Н (45%), α-d-Galp3OMe (37%) or α-d-Galp2,3OMe (18%).The anionic cell wall components of three other strains are represented by teichuronic acids with a rare constituent, viz., a diaminosugar, 2,3-diacetamido-2,3-dideoxyglucopyranose. The structures of their repeating units differ in the nature of the acidic components:→4)-β-d-Manp2,3NAcA-(1→6)-α-d-Glcp2,3NAc-(1→ (VKM Ас-2538 and VKM Ас-2540) and →4)-β-d-ManpNAcA-(1→6)-α-d-Glcp2,3NAc-(1→ (VKM Ас-2539).The structures of all the glycopolymers were established by chemical and NMR spectroscopic methods; they are identified in Gram-positive bacteria for the first time.     

Reactivity studies of highly electrophilic ruthenium complexes

The 16-electron, coordinatively unsaturated, dicationic ruthenium complex [Ru(P(OH)₂(OMe))(dppe)₂][OTf]₂ (1a) brings about the heterolysis of the C-H bond in phenylacetylene to afford the phenylacetylide complex trans-[Ru(CCPh)(P(OH)₂(OMe))(dppe)₂][OTf] (2). The phenylacetylide complex undergoes hydrogenation to give a ruthenium hydride complex trans-[Ru(H)(P(OH)₂(OMe))(dppe)₂][OTf] (3) and phenylacetylene via the addition of H₂ across the Ru-C bond. The 16-electron complex also reacts with HSiCl₃ quite vigorously to yield a chloride complex trans-[Ru(Cl)(P(OH)₂(OMe))(dppe)₂][OTf] (4). On the other hand, the other coordinatively unsaturated ruthenium complex [Ru(P(OH)₃)(dppe)₂][OTf]₂ (1b) reacts with a base N-benzylideneaniline to afford a phosphonate complex [Ru(P(O)(OH)₂)(dppe)₂][OTf] (5) via the abstraction of one of the protons of the P(OH)₃ ligand by the base. The phenylacetylide, chloride, and the phosphonate complexes have been structurally characterized. The phosphonate complex reacts with H₂ to afford the corresponding dihydrogen complex trans-[Ru(η²-H₂)(P(O)(OH)₂)(dppe)₂][OTf] (5-H₂). The intact nature of the H-H bond in this species was established using variable temperature ¹H spin-lattice relaxation time measurements and the observation of a significant J(H,D) coupling in the HD isotopomer trans-[Ru(η²-HD)(P(O)(OH)₂)(dppe)₂][OTf] (5-HD).     

Synthesis, structures and luminescent behaviour of tridentate salicylaldiminato-type borate complexes

Treatment of the ligands 3,5-tBu₂-2-(OH)C₆H₂CHNR [R = 2-(CO₂H)C₆H₄ (1a) and 2-(CO₂H)C₁₀H₆ (1b)] with trimethylborate, B(OMe)₃, in toluene yields, after work-up, the yellow crystalline complexes {[3,5-tBu₂-2-(O)C₆H₂CHNR]B(OMe)} [R = 2-(CO₂)C₆H₄ (2a) and 2-(CO₂)C₁₀H₆ (2b)], respectively. Further treatment of these complexes with trifluoromethanesulfonic (triflic) acid, CF₃SO₃H, followed by recrystallisation from tetrahydrofuran (thf) afforded the triflate salts [{3,5-tBu₂-2-(O)C₆H₂CHNR}B(thf)][CF₃SO₃] [R = 2-(CO₂)C₆H₄ (3a) and 2-(CO₂)C₁₀H₆ (3b)]. An electroluminescent device was constructed using 2a, which produced orange-green light with broad emission spectra (maximum brightness of 5 cd/m² being observed at 13 V). Compounds 1a and 2b·2MeCN have been characterised by single crystal X-ray structure determinations.     

Development of selective inhibitors for the treatment of rheumatoid arthritis: (R)-3-(3-(Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)pyrrolidin-1-yl)-3-oxopropanenitrile as a JAK1-selective inhibitor

A series of 3(R)-aminopyrrolidine derivatives were designed and synthesized for JAK1-selective inhibitors through the modification of tofacitinib’s core structure, (3R,4R)-3-amino-4-methylpiperidine. From the new core structures, we selected (R)-N-methyl-N-(pyrrolidin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine as a scaffold for further SAR studies. From biochemical enzyme assays and liver microsomal stability tests, (R)-3-(3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)pyrrolidin-1-yl)-3-oxopropanenitrile (6) was chosen for further in vivo test through oral administration. Compound 6 showed improved selectivity for JAK1 compared to that of tofacitinib (IC₅₀ 11, 2.4?×?10², 2.8?×?10³, and 1.1?×?10²?nM for JAK1, JAK2, JAK3, and TYK2, respectively). In CIA and AIA model tests, compound 6 exhibited similar efficacy to tofacitinib citrate.     

Palladium complexes with hydrophosphorane ligands (HP∼O and HP∼N), catalysts for Heck cross-coupling reactions

The synthesis and structural characterization of palladium complexes 1-3 incorporating H-spirophosphorane HP(OCMe₂CMe₂O)₂ and H-phosphonate congener HP(O)(OCMe₂CMe₂O) ligands are reported. The chemical composition of the complexes [PdCl(μ-Cl){P(OCMe₂CMe₂O)OCMe₂CMe₂OH}]₂ (1), [Pd{P(O)(OCMe₂CMe₂O)}₂]_n (2), and [Pd(μ-Cl){P(OCMe₂CMe₂O)OH}{P(OCMe₂CMe₂O)O}]₂ (3) was established by means of NMR, IR, ESI-MS spectroscopic methods. The relative stereochemistry of 1 and 3 was unambiguously determined by single X-ray diffraction studies. It was proved that complexes 1-3, and complex [PdCl₂P(OCH₂CMe₂NH)OCH₂CMe₂NH₂] (4) previously described in the literature, are very efficient catalysts for the Heck cross-coupling of bromobenzene with n-butyl acrylate. Moreover, they were also found to be effective catalysts in the stereoselective synthesis of trans-stilbenes.     

3- and 6-Substituted 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines as A1 adenosine receptor allosteric modulators and antagonists

A series of 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines were prepared and evaluated as potential allosteric modulators at the A₁ adenosine receptor. The structure–activity relationships of the 3- and 6-positions of a series of 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines were explored. Despite finding that 3- and 6-substituted 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines possess the ability to recognize an allosteric site on the agonist-occupied A₁AR at relatively high concentrations, the structural modifications we have performed on this scaffold favor the expression of orthosteric antagonist properties over allosteric properties. This research has identified 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines as novel class of orthosteric antagonist of the A₁AR and highlighted the close relationship between structural elements governing allosteric modulation and orthosteric antagonism of agonist function at the A₁AR.     

Glycolysis in human erythrocytes containing elevated concentrations of 2,3-P2-glycerate

In studies on the mechanism of the inhibitory effect of 2,3-diphosphoglycerate on glycolysis in human erythrocytes, the following results were obtained:1) Glucose consumption and lactate production are reduced by 70 and 40% relative to normal erythrocytes in red blood cells containing five times the normal amount of 2,3,-P₂-glycerate (“high-diphosphoglycerate” cells) at an extracellular pH of 7.4. The marked dependency of glycolysis on the extracellular pH observed in normal erythrocytes is almost completely lost in the “high-diphosphoglycerate” cells.2) About 50% of the inhibition of glycolysis in “high-diphosphoglycerate” cells can be accounted for by the 2,3-P₂-glycerate-induced decrease of the red-cell pH. This fall of the red-cell pH which occurs as a consequence of the Donnan effect of the non-penetrating 2,3-P₂-glycerate anion leads to a reduction of the glycolytic rate due to the properties of the enzyme phosphofructokinvse.3) The remaining part of the inhibitory effect must be attributed to an inhibition by 2,3-P₂-glycerate of glycolytic enzymes. From measurements of glycolytic rates and of the concentrations of glycolytic intermediates in the absence and presence of methylene blue it is concluded that the hexokinase reaction is inhibited by an elevation of 2,3-P₂-glycerate concentration. A marked increase of 3-P-glycerate concentration in “high-diphosphoglycerate” cells suggests that also the enzyme pyruvate kinase is inhibited by 2,3-P₂-glycerate.4) The dependencies of net-change of 2,3-P₂-glycerate concentration on the red-cell pH are identical in normal and “high-diphosphoglycerate” cells indicating that the balance between formation and decomposition of 2,3-P₂-glycerate is the same in erythrocytes with normal and very high concentrations 2,3-P₂-glycerate.     

Identification and characterization of xanthone biosynthetic genes contributing to the vivid red coloration of red-flowered gentian

Cultivated Japanese gentians traditionally produce vivid blue flowers because of the accumulation of delphinidin-based polyacylated anthocyanins. However, recent breeding programs developed several red-flowered cultivars, but the underlying mechanism for this red coloration was unknown. Thus, we characterized the pigments responsible for the red coloration in these cultivars. A high-performance liquid chromatography with photodiode array analysis revealed the presence of phenolic compounds, including flavones and xanthones, as well as the accumulation of colored cyanidin-based anthocyanins. The chemical structures of two xanthone compounds contributing to the coloration of red-flowered gentian petals were determined by mass spectrometry and nuclear magnetic resonance spectroscopy. The compounds were identified as norathyriol 6-O-glucoside (i.e., tripteroside designated as Xt1) and a previously unreported norathyriol-6-O-(6′-O-malonyl)-glucoside (designated Xt2). The copigmentation effects of these compounds on cyanidin 3-O-glucoside were detected in vitro. Additionally, an RNA sequencing analysis was performed to identify the cDNAs encoding the enzymes involved in the biosynthesis of these xanthones. Recombinant proteins encoded by the candidate genes were produced in a wheat germ cell-free protein expression system and assayed. We determined that a UDP-glucose-dependent glucosyltransferase (StrGT9) catalyzes the transfer of a glucose moiety to norathyriol, a xanthone aglycone, to produce Xt1, which is converted to Xt2 by a malonyltransferase (StrAT2). An analysis of the progeny lines suggested that the accumulation of Xt2 contributes to the vivid red coloration of gentian flowers. Our data indicate that StrGT9 and StrAT2 help mediate xanthone biosynthesis and contribute to the coloration of red-flowered gentians via copigmentation effects.     

Photo-oxygenation of polyhydroxyalkylfurans: rearrangement of O-acetyl derivatives

The photo-oxygenation of ethyl 2-methyl-5-(1,2,3,4-tetra-O-acetyl-d-lyxo-tetritol-1-yl)-3-furoate, ethyl 2-methyl-5-(1,2,3,4-tetra-O-acetyl-d-arabino-tetritol-1-yl)-3-furoate, 3-acetyl-2-methyl-5-(1,2,3,4-tetra-O-acetyl-d-arabino-tetritol-1-yl)furan, and ethyl 5-(1,4-di-O-acetyl-2,3-O-isopropylidene-d-lyxo-tetritol-1-yl)-2-methyl-3-furoate yielded the corresponding 1,4-endo-peroxides (3a–3d as pairs of diastereomers). Each diastereomer of the pairs 3a and 3d was isolated by fractional crystallisation. The rearrangement of the endo-peroxides at room temperature, by dissolution in CDCl₃, yielded the corresponding diepoxides and monoepoxides. The reduction of 3a–3d with methyl sulphide yielded the corresponding γ-diketones, ethyl (E)-2-C-acetyl-5,6,7,8-tetra-O-acetyl-2,3-dideoxy-d-lyxo-oct-2-en-4-ulosonate, ethyl (E)-2-C-acetyl-5,6,7,8-tetra-O-acetyl-2,3-dideoxy-d-arabino-oct-2-en-4-ulosonate, 3-C-acetyl-6,7,8,9-tetra-O-acetyl-1,3,4-trideoxy-d-arabino-non-3-eno-2,5-diulose, and ethyl (E)-2-C-acetyl-5,8-di-O-acetyl-2,3-dideoxy-6,7-O-isopropylidene-d-lyxo-oct-2-en-4-ulosonate, which can isomerise into the corresponding Z isomers.     

Synthesis of novel 2-amino-4-(5′-substituted 2′-phenyl-1H-indol-3′-yl)-6-aryl-4H-pyran-3-carbonitrile derivatives as antimicrobial and antioxidant agents

As a part of systematic investigation of synthesis and biological activities of indole analogues linked to various heterocyclic systems, we have synthesized new compounds viz., 2-amino-4-(5′-substituted 2′-phenyl-1H-indol-3′-yl)-6-aryl-4H-pyran-3-carbonitriles (2a–i), 4,5-diamino-6-(5′-substituted 2′-phenyl-1H-indol-3′-yl)-8-aryl-2-oxo-2,6-dihydrodipyrano [2,3-b:3,2-e]pyridine-3-carbonitriles (3a–i), 4-amino-5-(5′-substituted 2′-phenyl-1H-indol-3-yl)-7-aryl-1H-pyrano[2,3-d]pyrimidin-2(5H)-ones (4a–i), 4-amino-5-(5′-substituted 2′-phenyl-1H-indol-3′-yl)-7-aryl-1H-pyrano[2,3-d]pyrimidin-2(5H)-thiones (5a–i), 4-(5′-subtituted 2′-phenyl-1H-indol-3′-yl)-6-aryl-1,4-dihydropyrano[2,3-c]pyrazol-3-amines (6a–i) and 5-(5′-substituted 2′-phenyl-1H-indol-3′-yl)-7-aryl-3H-pyrano[2,3-d]pyrimidin-4(5H)-ones (7a–i). Antibacterial activity results revealed that, compound 6a showed promising activity versus Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae. Compound 6d exhibited good activity against S. aureus, K. pneumoniae and Pseudomonas aeruginosa. Antifungal activity results indicated that, compound 4d exhibited maximum zone of inhibition against Aspergillus oryzae and Aspergillus flavus. In case of antioxidant activity, compound 4a showed promising radical scavenging activity, ferric ions (Fe³⁺) reducing antioxidant power (FRAP) and metal chelating activity.     

Facile synthesis and characterization of μ-chloro, azido, thiocyanato bridged cyclometallated Pd(II) containing Schiff-base ligands

μ-Chloro bridged dinuclear cyclometallated Pd(II) complexes [Pd{(4-R)C₆H₃CHNC₆H₃-2,6-i-Pr₂}(μ-Cl)]₂ (R = H, OMe) were prepared by reaction of Na₂PdCl₄ with benzylideneanilines. Unexpectedly, Na₂PdCl₄ reacted with Schiff-bases bearing a furyl or a thienyl ring to give N-coordinated non-cyclometallated Pd(II) species [Pd(C₄H₃XCHNC₆H₃-2,6-i-Pr₂)₂Cl₂] (X = O, S). Treating [Pd{(4-R)C₆H₃CHNC₆H₃-2,6-i-Pr₂}(μ-Cl)]₂ (R = H, OMe) with an excess of NaN₃ or NH₄SCN generated μ-N₃ bridged or μ-SCN bridged cyclometallated Pd(II) complexes [Pd{(4-R)C₆H₃CHNC₆H₃-2,6-i-Pr₂}(μ-Y)]₂ (R = H, OMe; Y = N₃, NCS). The complexes were characterized by FTIR, NMR spectroscopy, elemental analysis and X-ray crystallography.