N-{2-(4-methoxyphenyltelluro)ethyl}morpholine (L1) and its platinum(II) and ruthenium(II) complexes. Synthesis and crystal structure of L1 and trans-[PtCl2(L1)2]

The first tellurated derivative of morpholine, N-{2-(4-methoxyphenyltelluro)ethyl}morpholine (L¹) has been synthesized by reacting in situ generated ArTe⁻ with 4-(2-chloroethyl)morpholine hydrochloride under N₂ atmosphere. The compound L¹ gives molecular ion peak at m/z 351 and is characterized structurally. The donor atoms N and Te in compound L¹ are rightly oriented for its ligation in bidentate mode. The TeC(alkyl) is 0.02 Å longer than TeC(aryl). The complexes of ligand L¹ having composition [PtCl₂(L¹)₂] (1) and [RuCl₂(p-cymene)L¹] (2) have been synthesized. The compound 1 has been characterized structurally. The Pt has a square planar geometry in complex 1 and two molecules of ligand L¹ bonded through Te alone are trans to each other (PtTe=2.583(2) Å). The ¹³C{¹H} NMR spectrum of complex 1 is as expected. The ¹H NMR spectrum of single crystals of complex 1 shows multiplication of signals, which is supported by HETCOR experiments. The complex 2 also has ligand L¹ in a monodentate coordination mode, bonded through Te alone. This is supported by deshielded CH₂Te and ArCTe signals in ¹H and ¹³C{¹H} NMR spectra of complex 2 with respect to those of free ligand L¹. The HETCOR spectrum of complex 2 has been used to authenticate the assignments of CH₂Te group, as its two protons appear to be magnetically non-equivalent.     

Eudistomidin G,a new β-carboline alkaloid from the Okinawan marine tunicate Eudistoma glaucus and structure revision of eudistomidin B

A new β-carboline alkaloid, eudistomidin G (1), has been isolated from the Okinawan marine tunicate Eudistoma glaucus, and the structure was elucidated from spectroscopic data. Furthermore, the structure of eudistomidin B (2), which has been isolated from the same tunicate, was revised from 2a to 2b by detailed analyses of spectroscopic data. Asymmetric synthesis of the revised structure (2b) of eudistomidin B (2) and its (1S,10S)-diastereomer (2c) has been accomplished with the Noyori catalytic asymmetric hydrogen-transfer reaction. The absolute configuration of eudistomidin B (2) was confirmed to be 2b possessing (1R,10S)-configuration, from comparison of the ¹H NMR data, CD spectra, [α]_D values, and HPLC analysis of 2b, 2c, and natural eudistomidin B.     

4-(2′-Carboxyphenyl)-4-oxobutyrate: An obligatory intermediate in lawsone biosynthesis

4-(2′-Carboxyphenyl)-4-oxobutyric acid (6) has been detected in cuttings of Impatiens balsamina. It is labelled under conditions where activity from U-¹⁴C-glutamate is incorporated effectively into lawsone (1). 3-(2′-Carboxyphenyl)-3-oxopropionic acid (7) has also been encountered in the cuttings.     

Three new compounds isolated from the bulbs of Fritillaria pallidiflora Schrenk and their anti-inflammatory activity

Three new compounds, 17β-cevanin-6-oxo-5α,20β-diol yibeinine (1), 2-(tetrahydro-5-(2-hydroxyphenyl)-2H-pyran-3-yl) phenol (2), 1,3-O-diferuloyl-2-methoxypropane diol (3), as well as four known compounds (4–7), have been isolated from the ethanol extract of dried bulbs of Fritillaria pallidiflora Schrenk. All structures were determined based on their spectroscopic data (1D and 2D NMR (including ¹H NMR, ¹³C NMR, ¹H-¹H COSY, HMBC, HSQC, HSQC-TOCSY, and NOESY experiments), and MS). Biological evaluation showed that compounds 1–4 inhibited the production of nitric oxide (NO) in LPS-stimulated RAW 264.7 cells with IC₅₀ values of 18.0, 38.7, 29.5, and 47.1 μM, respectively. These results indicated that compound 1 has potential anti-inflammatory activity.     

Conformational difference in the solid state and in solution of methyl 2,3,4-trideoxy-2,4-di-C-methyl-6-O-trityl-α-d-lyxo-hexopyranoside

The conformational difference of the title compound (1) in the solid state and in solution has been investigated by X-ray crystallography and high-field proton n.m.r. spectrometry. In the solid state, compound 1 adopts the ⁴C₁(d) conformation (1a), whereas 1 exists preferentially in the ¹C₄(d) conformation (1b) in chloroform solution.     

Synthesis and characterization of three geometric isomers of ruthenium(2,2-bipyridyl)(salicylaldehyde)2

A new synthesis of Ru^II(bpy)(sal)₂ (1) (bpy=2,2^′-bipyridyl, sal=salicylaldehyde) has been developed and the separation and characterization of all three geometric isomers have been completed. The isomers are denoted 1a (phenolic oxygens trans), 1b, (aldehyde oxygens trans), and 1c (aldehyde oxygen trans to phenolic oxygen). All three isomers have been characterized by ¹H NMR, high resolution FAB-MS, UV-Vis, and cyclic voltammetry. Additionally, 1a has been characterized by solid-state UV-Vis and a single-crystal X-ray structural study. The solid-state packing of the Ru^II(bpy)(sal)₂ molecules in the structure of 1a displays intermolecular π-π interactions between bpy ligands of adjacent molecules. The bpy interactions form infinite π-stacks with alternating short stacking distances of 3.437 and 3.402 Å.     

Acid-base properties of 4-nitro-l-histidine and related compounds

Acid-base properties of 4-nitro-l-histidine (3), N^α-acetyl-4-nitro-l-histidine (2), and N^α-acetyl-4-nitro-l-histidine methyl ester (1) are studied. Their pK_a^II values can be conveniently determined by ultraviolet spectroscopy. Potentiometric titration and ¹H-nuclear magnetic resonance (nmr) titration can also be used. Introduction of a nitro group strongly enhances the acidity of all the compounds. pK_a¹ of compound (3) has been also spectrophotometrically determined. Observed differences in acidity, in those cases where solvation does not play a major role, can be explained by assessing the influence of electrostatic charges on pK_a following Bjerrum's general theory with the aid of data from ¹H-nmr conformational analysis.     

Synthesis and characterization of a chiral Schiff base containing α-d-altropyranoside unit and its zinc(II) complex

A novel chiral Schiff base containing α-d-altropyranoside unit, methyl 4,6-O-benzylidene-3-deoxy-3-(2-salicylideneaminoethylamino)-α-d-altropyranoside (3, Me-Alt-NNOH), has been prepared. Treatment of zinc chloride with 3 in the presence of triethylamine afforded a five-coordinated zinc(II) complex [Zn(Me-Alt-NNO)Cl] (4). Both 3 and 4 have been characterized by infrared, ¹H NMR, ¹³C NMR, MS, and elemental analysis. The crystal structure of 4 has been determined by X-ray diffraction. Crystal structure analysis shows that the complex 4 exits a distorted triangular bipyramid geometry and the Schiff base motif acts as a uninegatively charged tetradentate chelating agent. The methoxy and amino groups cis-chelate to the zinc atom and the pyrano-ring is in an ideal ⁴C₁ chair conformation.     

Regioselectivity in the glycosylation of 5-(3-chlorobenzo[b]thien-2-yl)-4H-1,2,4-triazole-3-thiol

The glycosylation of 5-(3-chlorobenzo[b]thien-2-yl)-4H-1,2,4-triazole-3-thiol (1) and its 3-benzylsulfanyl and 3-methylsulfanyl derivatives with different glycosyl halides 2-4 has been studied in presence of base. The S-glycosides 5-7 were obtained in the presence of triethylamine, whereas the respective S,N⁴-bis(glycosyl) derivatives 8-10 were synthesized in the presence of potassium carbonate; the S,N²-bis(glycosyl) isomer 11 could also be isolated in the case of the galactosyl analog. Similarly, after protecting 1 as 3-benzyl(methyl)sulfanyl derivatives 12 or 13, the N⁴-glycosyl analogs 14-19 as well as minor amounts of S,N²-bis(galactosyl) isomers 20 and 21 were formed. The theoretical calculations using AM1 semiempirical methods agreed with the experimental results. Microwave irradiation (MWI) led to higher yields in much less time than the conventional methods, and no change in regioselectivity has been noticed.     

Antifungal activity of alkyl and heterocyclic aza-derivatives of gossypol as well as their complexes with NaClO4 against Fusarium oxysporum f. sp. lupini

Eight alkyl and six heterocyclic aza-derivatives of gossypol (2–15) have been synthesized using gossypol (1) extracted from Gossypium Herbaceum cottonseeds. The ability of gossypol aza-derivatives to form complexes with NaClO₄ has been investigated by electrospray ionisation (ESI) mass spectra recorded in the positive and negative ion detection modes. The gossypol aza-derivatives have been characterized by FT-IR, ¹H and ¹³C NMR spectroscopic methods and subsequently tested for their antifungal properties against Fusarium oxysporum. Four alkyl aza-derivatives (2–5), present in the enamine–enamine tautomeric form, have shown activity comparable or higher than that of gossypol against this fungus. To improve the antifungal activity the complexes of the most active compounds 2–5 with NaClO₄ were prepared. Complexes of 2 and 5 with NaClO₄ have shown antifungal activity higher than that of the uncomplexed compounds.     

Discrete and infinite metal–organometallic coordination networks consisting of europium(III) nodes and quinone π-complexes as spacers

The reaction of the organometalloligand [(η⁴-benzoquinone)Mn(CO)₃]⁻ (p-QMTC) with Eu³⁺ nodes has been utilized to generate the discrete and polymeric supramolecular metal–organometallic coordination networks [Eu(DMSO)(NO₃)₂(p-QMTC)₂]₂ (1) and the polymeric [Eu(p-QMTC)₃]_∞ (2). The X-ray structures of 1 and 2 are reported.     

Cytotoxic palladium(II) complexes of 8-aminoquinoline derivatives and the interaction with human serum albumin

Palladium(II) complexes are potential antitumor metallodrugs for their chemical resemblance to platinum(II) complexes. Two palladium(II) complexes (1 and 2) in the formula of [PdLⁿCl] [L¹ = N-(tert-butoxycarbonyl)-l-methionine-N′-8-quinolylamide, L² = L-alanine-N′-8-quinolylamide] have been synthesized accordingly. The structures of the complexes were fully characterized by X-ray crystallography. The palladium(II) center in 1 is coordinated by two N atoms and an S atom from L¹ with one chloride anion as the leaving group; while that in 2 is coordinated by three N atoms from L² with one chloride anion as the leaving group. The interaction between complex 1 and human serum albumin (HSA) has been investigated using fluorescence and circular dichroism spectroscopies. The complex seems to react with HSA chiefly through hydrophobic and electrostatic interactions, and it does not alter the α-helical nature of HSA. The cytotoxicity of these complexes has been tested against the human cervical cancer (HeLa), human mammary cancer (MCF-7), and human lung cancer (A-549) cell lines. Complex 1 displays a cytotoxic activity comparable to that of cisplatin, but complex 2 is less active than cisplatin.     

Synthesis and evaluation of new endomorphin analogues modified at the Pro2 residue

Six new endomorphin analogues, incorporating constrained amino acids in place of native proline have been synthesized. Residues of (S)-azetidine-2-carboxylic acid (Aze), 3,4-dehydro-(S)-proline (Δ³Pro), azetidine-3-carboxylic acid (3Aze) and dehydro-alanine (ΔAla) have been used to prepare [Δ³Pro²]EM-2 (1), [Aze²]EM-1 (2), [Aze²]EM-2 (3), [3Aze²]EM-1 (4), [3Aze²]EM-2 (5) and [ΔAla²]EM-2 (6). Binding assays and functional bioactivities for μ- and δ-receptors are reported. The highest affinity, bioactivity and selectivity are shown by peptides 2 and 3 containing the Aze residue.     

Design and synthesis of some new quinoline-3-carbohydrazone derivatives as potential antimycobacterial agents

A series of 26 new quinoline derivatives carrying active pharmacophores has been synthesized and evaluated for their in vitro antituberculosis activity against Mycobacterium tuberculosis H37Rv (MTB), Mycobacterium smegmatis (MC²), and Mycobacterium fortuitum following the broth micro dilution assay method. Compounds 13e, 13i, 13k, 14a, 14c, 14i, and 14k exhibited significant minimum inhibition concentrations, when compared with first line drugs isoniazid (INH) and rifampicin (RIF) and could be ideally suited for further modifications to obtain more efficacious compounds in the fight against multi-drug resistant tuberculosis.     

A comparison of the coordination of two linkage isomers of bis(1-methylthioimidazolyl)methane to zinc salts

A structural comparison of the coordination chemistry of the two linkage isomeric forms of bis(1-methylthioimidazolyl)methane, [H₂C(N-mt)₂] (L^S), and [H₂C(S-mt)₂] (L^N) to a number of zinc complexes has been carried out. The complexes ZnX₂L^S and ZnX₂L^N (where X = Cl, Br and I) have all been prepared in good to high yields and have been characterised by spectroscopic and analytical methods. X-ray crystallography studies were also carried out on all of the newly prepared compounds, revealing κ²-SS and κ²-NN coordination modes for L^S and L^N containing complexes, respectively.     

Design,synthesis, anti-inflammatory activity and molecular docking of potential novel antipyrine and pyrazolone analogs as cyclooxygenase enzyme (COX) inhibitors

As a part of a directed program for development of new active agents, novel heterocyclic derivatives with antipyrine and pyrazolone moieties -incorporated in- have been designed and synthesized. Starting with 4-arylidene-3-methyl-1-phenyl-5-pyrazolone derivative 2a,b novel Mannich bases derivatives have been synthesized and biologically evaluated for their anti-inflammatory activity. Furthermore, the activity of such compounds has been tested interestingly as COX-1 and COX-2 inhibitors. Structure elucidation of the synthesized compounds was attained by the use of elemental analysis, IR, ¹H NMR, ¹³C NMR, and Mass spectrometry techniques. Compounds 3b, 3d and 4b represent the high % inhibition values for both COX-1 and COX-2. On the other hand, compound 8 showed little selectivity against COX-2 while compound 10 showed good selectivity against COX-1 only. Structure activity relationship has been discussed and the results were confirmed by molecular docking calculations.     

Competitive neutrophil elastase inhibitory isoflavones from the roots of Flemingia philippinensis

Flemingia philippinensis has been used throughout history to cure rheumatism associated with neutrophil elastase (NE). In this study, we isolated sixteen NE inhibitory flavonoids (1–16), including the most potent and abundant prenyl isoflavones (1–9), from the F. philippinensis plant. These prenyl isoflavones (2, 3, 5, 7, and 9) competitively inhibited NE, with IC₅₀ values of 1.3–12.0 μM. In addition, they were reversible, simple, slow-binding inhibitors according to their respective parameters. Representative compound 3 had an IC₅₀ = 1.3 μM, k₃ = 0.04172 μM⁻¹ min⁻¹, k₄ = 0.0064 min⁻¹, and K_i^app = 0.1534 μM. The K_ik/K_iv ratios (18.5 ∼ 24.6) for compound 3 were consistent with typical competitive inhibitors. The prenyl functionality of isoflavones significantly affected inhibitory potencies and mechanistic behavior by shifting the competitive mode to a noncompetitive one. The remaining flavonoids (10–16) were confirmed as mixed type I inhibitors that preferred to bind free enzyme rather than the enzyme-substrate complex. Fluorescence quenching analyses indicated that the inhibitory potency (IC₅₀) closely followed the binding affinity (K_SV).     

Proton magnetic resonance studies of 9-(β-d-xylofuranosyl)adenine 3′,5′-cyclic monophosphate and 9-(β-d-arabinofuranosyl)adenine 2′,5′-cyclic monophosphate

A detailed ¹H 220-MHz n.m.r. study of 9-(β-d-xylofuranosyl)adenine 3′,5′-cyclic monophosphate (3′,5′-xylo-cAMP, 1) and 9-(?-d-arabinofuranosyl)adenine 2′,5′-cyclic monophosphate (2′,5′-ara-cAMP, 2) in D₂O solution is described. The sugar-ring conformations in 1 and 2 are shown to be ³E and ²E, respectively, and the phosphate rings are in a chair form. An unusual ⁴J_P,H coupling of 2.4 Hz is observed between H-4′ and phosphorus in 1 and a vicinal J_P,H of 30.8 Hz between H-5′ and phosphorus in 2. This latter coupling verifies a similar value found previously in the ara-cytidine analog of 2. A comparison of the conformational properties of cyclic nucleotides having fused phosphate and sugar rings has been made, together with an assessment of the use of the Karplus constants in such ring-systems.     

Biotransformation of dehydroepiandrosterone (DHEA) with Penicillium griseopurpureum Smith and Penicillium glabrum (Wehmer) Westling

Microbial transformation of dehydroepiandrosterone (DHEA, 1) using Penicillium griseopurpureum Smith and Penicillium glabrum (Wehmer) Westling has been investigated. Neither fungi had been examined previously for steroid biotransformation. One novel metabolic product of DHEA (1) transformed with P. griseopurpureum Smith, 15α-hydroxy-17a-oxa-d-homo-androst-4-ene-3,17-dione (5), was reported for the first time. The steroid products were assigned by interpretation of their spectral data such as ¹H NMR, ¹³C NMR, IR, and HR-MS spectroscopy. P. griseopurpureum Smith was proven to be remarkably efficient in oxidation of the DHEA (1) into androst-4-en-3,17-dione (2). The strain was also observed to yield different monooxygenases to introduce hydroxyl groups at C-7α, -14α, and -15α positions of steroids. Preference for Baeyer–Villiger oxidation to lactonize D ring and oxidation of the 3β-alcohol to the 3-ketone were observed in both incubations. The strain of P. glabrum (Wehmer) Westling catalyzed the steroid 1 to generate both testololactone 3, and d-lactone product with 3β-hydroxy-5-en moiety 8. In addition, the strain promoted hydrogenation of the C-5 and C-6 positions, leading to the formation of 3β-hydroxy-17a-oxa-d-homo-5α-androstan-3,17-dione (9).The biotransformation pathways of DHEA (1) with P. glabrum (Wehmer) Westling and P. griseopurpureum Smith have been investigated, respectively. Possible metabolic pathways of DHEA (1) were proposed.