1,6-diamino-2,5-anhydro-1,6-dideoxy-l-iditol and some derivatives thereof

1,6-Diamino-2,5-anhydro-1,6-dideoxy-l-iditol (31) and its derivatives were synthesized, starting from 2,4-O-benzylidene-1,6-di-O-tosyl-d-glucitol. The 1,6-bis-(acetamido)-l-talo epoxide was readily hydrolyzed to the corresponding l-iditol derivative under anchimeric assistance of the 1-acetamido group. On treatment with formaldehyde-formic acid, diamine 31 gave a tricyclic, 1,4:3,6-bis(N,O-methylene) derivative which was stable under acidic conditions but, according to ¹³C-n.m.r. spectroscopy, was readily hydrolyzed to an equilibrium mixture in neutral, aqueous solution. The corresponding 1,6-bis(dimethylamino) derivative could be obtained by reducing this equilibrium mixture with borohydride. The different, quaternary salts obtained on methylation of the corresponding 1,6-bis(dimethylamino) derivatives with methyl iodide (aiming at the structure of epi-allo-muscarine) showed no muscarine-like, biological activity.     

Preparation, spectroscopy, X-ray analysis, and water-solubility studies of the first bis-PTA (PTA = 1,3,5-triaza-7-phosphaadamantane) derivatives

The bis-phosphines, 1,1′-[1,2-phenylenebis(methylene)]bis-3,5-diaza-1-azonia-7-phosphatricyclo[3.3.1.1]decane dibromide (1), 1,1′-[1,3-arenebis(methylene)]bis-[3,5-diaza-1-azonia-7-phosphatricyclo [3.3.1.1]decane dibromide (arene = phenyl (2), tolyl (3), anisolyl (4)), and 1,1′-[1,4-phenylenebis(methylene)]bis-3,5-diaza-1-azonia-7-phosphatricyclo[3.3.1.1]decane dibromide (5) were prepared in over 90% yield by refluxing 1,2-bis(bromomethyl)benzene, 1,3-bis(bromomethyl)benzene, 1,3-bis(bromomethyl)-5-methyl-benzene, 1,3-bis(bromomethyl)-5-methoxy-benzene, and 1,4-bis(bromomethyl)benzene with 1,3,5-triaza-7-phosphaadamantane (PTA) in acetone or chloroform. Compounds 1-5 are the first phosphines reported that contain two PTA moieties. All five compounds were characterized by ESI-MS, elemental analysis, ¹H, ¹³C, and ³¹P NMR spectroscopy, while 3 and 4 were additionally analyzed via single crystal X-ray diffraction. The relative positions of the PTA units on the aromatic ring as well as the substituents of the ring had a pronounced effect on the water-solubilities of the systems. The ortho compound (1, 2000 mg/mL) was more than two orders of magnitude more soluble than the para compound (5, 12.5 mg/mL). The meta substituted phenyl (2) and tolyl (3) compounds had solubilities (810 mg/mL) that were more than triple that of PTA (235 mg/mL) while the anisolyl analog (4) was half as soluble (121 mg/mL).     

Synthesis and characterization of alkynes β-diketonate copper(I) complexes

The reactions of 1,3,5-tris-(trimethylsilylethynyl)benzene (1) with Cu₂O and 1,1,1,5,5,5,-hexafluoroacetylacetone in alkyne to Cu ratios 1:0.5, 1:1 and 1:3 in CH₂Cl₂ at room temperature give copper complexes (η²-1,3,5-tris(trimethylsilylethynyl)benzene)(Cu(hfac)) (2), (η²:η²-1,3,5-tris(trimethylsilylethynyl)benzene)(Cu(hfac))₂ (3) and (η²:η²:η²-(1,3,5- tris(trimethylsilylethynyl)benzene))₂(Cu(hfac))₃(4), respectively. In the same conditions, 2,5-bis-(trimethylsilylethynyl)thiophene (5) reacts with 0.5 or 1 equiv. of Cu₂O to give (η²:η²-2,5-bis(trimethylsilylethynyl)thiophene)(Cu(hfac)) (6) and (η²:η²-2,5-bis(trimethylsilylethynyl)thiophene)(Cu(hfac))₂ (7), respectively, and 1,4-bis(trimethylsilyl)-1,3-butadiyne (8) with 0.5 equiv. of Cu₂O give (η²:η²-1,4-bis(trimethylsilyl)-1,3-butadiyne)(Cu(hfac))₂(9). All the new compounds have been characterized by analytical and spectroscopic methods and their thermal properties were examined by thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC).     

Hydrolysis of neutral phosphate and phosphonate esters catalysed by Co2+-chelates of tris-imidazolyl phosphines

The hydrolysis of two neutral phosphate esters, (tris-2-pyridylphosphate and tris-p-nitrophenylphosphate, 5 and 4 respectively) and a phosphonate ester (ethyl-p-nitrophenylmethylphosphonate (6)) were studied in the presence of Co²⁺-complexes of two tris- imidazolylphosphines. In the hydrolyses of both 5 and 6, the Co²⁺-complex of bis-[4,5-diisopropyl- imidazol-2-yl]imidazole-2-yl phosphine (2) appears to act as the anionic form, generated by ionization of a Co²⁺-bound H₂O having a pK_a of ～8 at 37 °C in 80% ethanol-H₂O. On the other hand, the Co²⁺-complex of bis-[4,5-diisopropylimidazol-2-yl]-4(5)- hydroxyethylimidazol-2-yl phosphine (3) catalyses the hydrolyses of 5 and 6 with an activity which increases linearly with pH. In this case, the active form of Co²⁺:3 has a pK_a in excess of 8.3 which apparently obtains from ionization of the Co²⁺- associated hydroxyethyl group. Evidence is presented that Co²⁺:3 functions as a general base catalyst in the hydrolysis of 5.     

Multimetallic compounds containing cyclometalated Ir(III) units: Synthesis, structure, electrochemistry and photophysical properties

The reaction of the cyclometalated Ir^III dimer [{(ppy)₂Ir}₂(μ-Cl)₂] (ppyH = 2-phenylpyridine) with silver triflate followed by a multidentate ligand [1,4-bis[3-(2-pyridyl)pyrazolylmethyl]benzene (bppb), 1,3,5-tri[3-(2-pyridyl)pyrazolylmethyl]-2,4,6-trimethylbenzene (tppb), 2,4,6-tris(2-pyridyl)-1,3,5-triazine (tptz), 2-chloro-4,6-bis(dipyridin-2-ylamino)-1,3,5-triazine (cddt) or 2,4,6-tris(dipyridin-2-ylamino)-1,3,5-triazine (tdat)] afforded di- or trinuclear compounds: [{Ir(ppy)₂}₂(μ-bppb)](OTf)₂ (1), [{Ir(ppy)₂}₃(μ-tppb)](OTf)₃ (2), [{Ir(ppy)₂}₂(μ-tptz-OH)](OTf) (3), [{Ir(ppy)₂}₂(μ-cddt)](OTf)₂ (4) and [{Ir(ppy)₂}₂(μ-tdat)](OTf)₂ (5). All of these compounds contain cationic metal cores with corresponding triflate counter anions. The molecular structures of 1-4 reveal that the structural feature of the Ir(ppy)₂ center of the starting precursor is conserved in the products. Also, because of the nature of the ligands, there is virtually no electronic communication between the Ir^III centers except in 3 where a ring hydroxylation at the triazine carbon atom is effected upon metalation. Compounds 1-5 are robust in solution where they retain their structural integrity. The UV-Vis and emission spectra of 1-5 compounds are very similar to each other with the exception of 3 which seems to possess a different electronic structure. All the compounds are luminescent at room temperature. The emission bands indicate significant contribution from ³LC. Increase in the number of ‘Ir(ppy)₂’ units does not have any effect on emission color.     

Cadmium(II) and zinc(II) coordination polymers with mixed building blocks of benzenedicarboxyl and 2,5-bipyridyl-1,3,4-oxadiazole: Syntheses, crystal structures, and properties

Three Cd(II) and Zn(II) coordination polymers, including {[Cd(3-bpo)(mip)(H₂O)](H₂O)₂}_n (1), {[Cd(4-bpo)(hip)(H₂O)](H₂O)₄}_n (2), and {[Zn(4-bpo)(tp)](CH₃OH)}_n (3) were synthesized from the reactions of Cd^II or Zn^II nitrate with mixed organic ligands [3-bpo = 2,5-bis(3-pyridyl)-1,3,4-oxadiazole, H₂mip = 5-methylisophthalic acid, 4-bpo = 2,5-bis(4-pyridyl)-1,3,4-oxadiazole, H₂hip = 5-hydroxylisophthalic acid, H₂tp = terephthalic acid] under the similar layered diffusion condition. The resulting crystalline materials 1-3 were characterized by IR, microanalysis, powder X-ray diffraction (PXRD) techniques. Single-crystal X-ray diffraction indicates a 1-D tubular motif for 1, a 1-D dual-track array for 2, and a 2-D grid-like pattern for 3, constructed via different metal-ligand coordination contacts. Higher-dimensional supramolecular architectures are further assembled in 1-3 via H-bonding and aromatic stacking interactions. In addition, thermal stability and fluorescence of these polymeric complexes were also investigated and discussed.     

Palladium(II) and platinum(II) complexes with polypyridylbenzene ligands

The ligands 1,3-bis(3-pyridyl)benzene (1), 1,3-bis(4-pyridyl)benzene (2) and 1,3,5-tris(4-pyridyl)benzene (3) have been prepared by Stille coupling of 3- or 4-trimethylstannylpyridine with the appropriate bromoarene. Ligands 1 and 2 react with [M(OTf)₂(dppp)] (M=Pd, Pt) to produce the dipalladium- or diplatinum-containing macrocycles [M₂(μ-1)₂(dppp)₂](OTf)₄ or [M₂(μ-2)₂(dppp)₂](OTf)₄. These have been characterized by NMR spectroscopy and mass spectrometry and, in the case of [Pd₂(μ-1)₂(dppp)₂](OTf)₄, by X-ray crystallography. The molecular structure of the [Pd₂(μ-1)₂(dppp)₂]⁴⁺ cation reveals a shallow arrangement of the aromatic rings, with the palladium atoms lying above and below. The tridentate ligand 3 reacts with [Pd(OTf)₂(dppp)] to produce a trimetallic species of the form [Pd₃(μ₃-3)₂(dppp)₃](OTf)₆.     

Nickel(II) complexes bearing a pincer ligand containing thioamide units: Comparison between SNS- and SCS-pincer ligands

Nickel(II) complexes bearing a κ³SNS pincer ligand, 2,5-bis(benzylaminothiocarbonyl)pyrrolyl (L1) and a κ³SCS-pincer ligand, 2,6-bis(benzylaminothiocarbonyl)phenyl (L2), were synthesized, and their structures and electrochemical properties were elucidated. The crystal structures of [Ni(SNS)Br] (2) and [Ni(SCS)Br] (5) were determined by X-ray crystallography. The electrochemical and crystallographic data obtained from the complexes revealed that the κ³SCS ligand has a stronger electron-donating ability than the κ³SNS ligand.     

Autohydrolysis of phytic acid.

The autohydrolysis of phytic acid at 120 degrees C resulted in the formation of most of the phosphate esters of myo-inositol in varying amounts depending upon the reaction time. Eighteen of the 39 chromatographically distinct myo-inositol mono-, bis-, tris-, tetrakis-, pentakis-, and hexakisphosphates have been characterized using two different HPLC systems. These myo-inositol phosphates were partially purified by preparative anion-exchange chromatography under acidic and alkaline elution conditions. The combination of these two methods provides a two-tiered chromatographic approach to the rapid and sensitive identification of inositol phosphates in complex mixtures. Identification of the products was confirmed by 1D and 2D (1)H NMR analysis. The analytical procedure was applied to the autohydrolysis of the mixture of inositol phosphates from corn steep water.     

Artemisinin-derived dimer phosphate esters as potent anti-cytomegalovirus (anti-CMV) and anti-cancer agents: A structure–activity study

We recently reported the anti-cancer and anti-cytomegalovirus (CMV) activity of artemisinin-derived trioxane diphenylphosphate dimer 838. To probe the relationship between chemical structure and anti-CMV and anti-cancer activities, we now report synthesis and evaluation of a series of eight new dimer phosphate ester analogs of 838. This series of novel molecules was screened against human foreskin fibroblasts (HFFs) infected with CMV and against the human Jurkat T cell acute lymphoblastic leukemia cell line. This SAR study confirms the very high anti-CMV and anti-cancer potencies of dimer diphenyl phosphate ester 838 without its being toxic to normal cells.     

Syntheses of 3-fluoro-, 3-epi-3-fluoro-, and 3,3-difluoro-3-de(methoxy)sporaricin A

3-Fluoro- (4), 3-epi-3-fluoro- (3), and 3,3-difluoro-3-de(methoxy)sporaricin A (5) have been prepared by reaction of diethylaminosulfur trifluoride with the corresponding precursors: 1,2′,6′-tris(N-benzyloxycarbonyl)-4-N, 5-O-carbonyl-3-de(O-methyl)sporaricin B (6), its 3-epi-3-hydroxy isomer (10), and the 3-oxo derivative (9). The structures of 3,4, and 5 were determined by ¹H-, ¹³C-, and ¹⁹F-n.m.r. spectroscopy.     

Synthesis, characterization and selective fluorescent zinc(II) sensing property of three Schiff-base compounds

Three Schiff-base compounds, 4-methyl-2,6-bis(1-(2-piperidinoethyl)iminomethyl)-phenol (HL¹), 4-methyl-2,6-bis(1-(2-pyrrolidinoethyl)- iminomethyl)-phenol (HL²) and (4-methyl-2,6-bis(1-(2-morpholinoethyl)iminomethyl)-phenol) (HL³), have been synthesized and characterized by elemental analysis, FT-IR, ¹H NMR, UV-Vis, electrospray ionisation mass and fluorescence spectroscopy. The emission quantum yield of the compounds increases by ca. 10-17 times by the addition of Zn²⁺ ion. Introduction of other metal ions of biological and environmental relevance either keeps unaltered or quenches the emission intensity of the ligands. This happens because of large binding constant (∼10⁴ M⁻¹) of the ligand with Zn²⁺ ion in acetonitrile. Each of the three ligands forms 1: 2 (ligand:metal) complexes which are characterized by single crystal X-ray diffraction analyses. This imposes rigidity to the ligand due to the complexation and, as a result, the radiative decay constant increases and the corresponding nonradiative decay parameter decreases. All of the ligands react with zinc chloride in acetonitrile to form dinuclear complexes which have been characterized by the elemental analysis, FT-IR, UV-Vis, electrospray ionisation mass spectroscopies and single crystal X-ray structural determinations.     

2,5:3,4-Dianhydro-1,6-dideoxy-6-(trimethylamino)-d-allitol and -d-galactitol

A new, four-step synthesis of 2,5:3,6-dianhydro-1-deoxy-d-glucitol 16 was worked out, starting from 1,6-dibromo-1,6-dideoxy-d-mannitol. Compound 16 was converted into different 4-O-acyl derivatives, the 3,6-anhydro rings of which where opened with hydrogen bromide, yielding the corresponding 6-bromo compounds. These were converted, via the 6-azides, into the 6-(dimethylamino) derivatives, the sulfonic esters of which gave, on treatment with base, the 2,5:3,4-dianhydro-d-allitol and -d-galactitol derivatives. These were converted with methyl iodide into the corresponding quaternary salts. On biological testing, only the d-allitol derivative showed weak, muscarine-like activity.     

Isolation of 2,5-anhydro-1,3-O-isopropylidene-6-O-trityl-D-glucitol and conformations of its 4-O-substituted and deprotected,acylated derivatives

Acidic dehydration of D-mannitol (1) gave a mixture of anhydrides (2) that was isopropylidenated and subsequently tritylated. A single component crystallized from the resulting mixture and was shown to be the novel 2,5-anhydro-1,3-O-isopropylidene-6-O-trityl-D-glucitol (4) by chemical and physical analysis and by comparison of its deprotected, dibenzoylated derivative (10) with authentic 2,5-anhydro-1,6-di-O-benzoyl-D-glucitol. Acid hydrolysis of 4 afforded pure 2,5-anhydro-D-glucitol (9) in better yield than by the previously reported route. The 4-O-acetyl (5), 4-O-chloro-acetyl (6), 4-O-methyl (7), and 4-O-(methylsulfonyl) (8) derivatives of 4, the tetra-O-acetyl (11) derivative of 9, and the 3,4-di-O-acetyl (12) derivative of 10, have been prepared and spectrally characterized. Complete proton-n.m.r. analysis yields first-order coupling constants that indicate the E₁ (D) conformation for the tetrahydrofuran ring and the chair conformation for the 1,3-dioxane ring of 4-2-8. Obtainable coupling constants suggest that 11 and 12 exist in the ^oE and/or ^oT₁, conformations.     

Synthesis, and characterization of cobalt(III) complexes with Schiff bases derived from 2-hydroxynaphthaldehyde, (naph)2dien and (naph)2dpt, and monodentate amine ligands: Crystal structure, spectral and redox properties

Two series of complexes of the type [Co^III{(naph)₂dien}(amine)]BPh₄ {(naph)₂dien = bis-(2-hydroxy-1-naphthaldimine)-N-diethylenetriamine dianion, and amine = piperidine (pprdn) (1), pyrrolidine (prldn) (2), pyridine (py) (3), N-methylimidazole (N-MeIm) (4)}, and [Co^III{(naph)₂dpt}(amine)]BPh₄ {(naph)₂dpt = bis-(2-hydroxy-1-naphthaldimine)-N-dipropylenetriamine dianion, and amine = piperidine (pprdn) (5), 3-methylpyridine (3-Mepy) (6)} have been synthesized and characterized by elemental analyses, IR, UV-Vis, and ¹H NMR spectroscopy. The crystal structures of (2) and (6) have been determined by X-ray diffraction. The redox potentials of the central cobalt ion show a relatively good correlation with the σ-donor ability of the axial ligands. The spectroscopic and electrochemical properties of these complexes are also influenced by the mutual steric hindrance between the pentadentate Schiff base and the ancillary ligands.     

Synthesis of an intensely sweet chlorodeoxysucrose: Mechanism of 4′-chlorination of sucrose by sulphuryl chloride

Reaction of 6-O-acetylsucrose¹ with sulphuryl chloride in chloroform-pyridine affords, after dechlorosulphation and acetylation, a mixture of two isomeric 2,3,6-tri-O-acetyl-4-chloro-4-deoxy-α-d-galactopyranosyl 3-O-acetyl-1,4,6-trichloro-1,4,6-trideoxy-β-d-hexulofuranosides (6 and 7) and 2,3,6-tri-O-acetyl-4-chloro-4-deoxy-α-d-galactopyranosyl 3,4-di-O-acetyl-1,6-dichloro-1,6-dideoxy-β-d-fructofuranoside (4). Chlorination of C-4, C-1′, and C-6′ occurs by direct displacement of the initially formed chlorosulphonyloxy groups by chloride ions, but displacement of the 4′-chlorosulphate is sterically hindered. The introduction of a 4′-chloro substituent involves ring opening of intermediate 3′,4′-epoxides by chloride ions, the ribo-epoxide producing the sorbo-isomer 6 and the lyxo-epoxide giving the fructo-isomer 7. The proposed mechanism is supported by the formation of 4-chloro-4-deoxyfructofuranosides when 3′,4′-lyxo-hexulofuranosides are treated with sulphuryl chloride under the same conditions.     

Phenolic compounds from parasitic Sapria himalayana f. albovinosa and Sapria myanmarensis (Rafflesiaceae) in Myanmar

Three anthocyanins, four flavonols, three aromatic acids and five gallotannins were isolated from Sapria himalayana f. albovinosa in Myanmar. They were identified as cyanidin 3-O-glucoside (1), cyanidin 3-O-xyloside (2) and peonidin 3-O-glucoside (3) (anthocyanins), quercetin 3-O-glucoside (4), quercetin 7-O-glucoside (5), quercetin 3-O-glucuronide (6) and isorhamnetin 3-O-glucoside (7) (flavonols), ellagic acid (8), gallic acid (9) and ethyl gallate (10) (aromatic acids), and 1,2,4,6-tetragalloylglucose (11), 1,4,6-trigalloylglucose (12), 1,2,6-trigalloylglucose (13), 1,2,4-trigalloylglucose (14) and 1,6-digalloylglucose (15) (gallotannins) by UV, LC-MS, acid hydrolysis, NMR and/or HPLC comparisons with authentic samples. The chemical composition of S. myanmarensis was qualitatively the same with that of S. himalayana f. albovinosa. Phenolic compounds of the Rafflesiaceae species including Sapria, Rafflesia and Rhizanthes were isolated and identified in this survey for the first time.     

Synthesis of new platinum(II) complexes containing hybrid thioether-pyrazole ligands: Structural analysis by H and C{H} NMR spectroscopy and X-ray crystal structures

Treatment of the ligands 1,8-bis(3,5-dimethyl-1-pyrazolyl)-3,6-dithiaoctane (bddo), 1,9-bis(3,5-dimethyl-1-pyrazolyl)-3,7-dithianonane (bddn), and 1,6-bis(3,5-dimethyl-1-pyrazolyl)-2,5-dithiahexane (bddh) with several platinum starting materials as K₂PtCl₄, PtCl₂, [PtCl₂(CH₃CN)₂] and [PtCl₂(PhCN)₂] was developed under different conditions. The reactions did not yield pure products. The ratio of the NSSN, NS, SS, NN, and 2NS isomers has been calculated through NMR experiments. Treatment of the mixtures of complexes with NaBPh₄ affords [Pt(NSSN)](BPh₄)₂ (NSSN = bddo, bddn). These Pt(II) complexes have been characterised by elemental analyses, conductivity measurements, IR and ¹H and ¹³C NMR spectroscopy. The X-ray structures of the complexes [Pt(NSSN)](BPh₄)₂ (NSSN = bddo, bddn) have also been determined. In these complexes, the metal atom is tetracoordinated by the two azine nitrogen atoms of the pyrazole rings and two thioether sulfur atoms. When the [Pt(NSSN)](BPh₄)₂ (NSSN = bddo, bddn) complexes were heated under reflux in a solution of Et₄NBr in CH₂Cl₂/CH₃OH (1:1), a mixture of isomers was obtained.     

Bis(benzoyl) phosphate inactivators of beta-lactamase C from Mtb

The class A β-lactamase BlaC is a cell surface expressed serine hydrolase of Mycobacterium tuberculosis (Mtb), one of the causative agents for Tuberculosis in humans. Mtb has demonstrated increased susceptibility to β-lactam antibiotics upon inactivation of BlaC; thus, making BlaC a rational enzyme target for therapeutic agents. Herein, we present the synthesis and structure-activity-relationship data for the 1st-generation library of bis(benzoyl) phosphates (1–10). Substituent effects ranged from σ_p = −0.27 to 0.78 for electronic and π = −0.41 to 1.98 for hydrophobic parameters. Compounds 1, 4 and 5 demonstrated the greatest inhibitory potency against BlaC in a time-dependent manner (k_obs = 0.212, 0.324, and 0.450 mn⁻¹ respectively). Combined crystal structure data and mass spectrometric analysis of a tryptic digest for BlaC inactivated with 4 provided evidence that the mechanism of inactivation by this bis(benzoyl) phosphate scaffold occurs via phosphorylation of the active-site Ser-70, ultimately leading to an aged form of the enzyme.     

Preparation of inositol phosphates from sodium phytate by enzymatic and nonenzymatic hydrolysis

Procedures for preparing myo-inositol bis-, tris-, tetrakis-, and pentakisphosphates from sodium phytate were established. Hydrolysis was achieved by autoclaving or enzymatic treatment; the inositol phosphates were separated by anion-exchange chromatography and were identified by fast atom bombardment-mass spectrometry. Enzymatic hydrolysis was more specific than autoclaving for isomer formation, whereas autoclaving was more efficient for producing the bis- and trisphosphates, which did not accumulate in significant amounts under the conditions of enzymatic hydrolysis. Sodium salts of the inositol phosphates were more powdery and less hygroscopic than the potassium salts. The procedures were satisfactory for producing gram quantities of each inositol phosphate, amounts adequate for animal studies of effects on mineral bioavailability.