Ultraviolet-visible spectroscopic study of ion-pairs of sodium and potassium monoethyl benzeneazophosphonates and their crown ether complexes in acetonitrile

The u.v.-vis spectroscopic study of ion-pairs of the sodium and potassium monoethyl ester of [α-(4-benzeneazoanilino)-N-benzyl] phosphoric acid, [α-(4-benzeneazoanilino)-N-4-hydroxybenzyl] phosphonic acid and [α-(4-benzeneazoanilino)-N-4-methoxybenzyl] phosphonic acid and their complexes with dibenzo-18-crown-6 and dibenzo-24-crown-8 is described. While the free sodium salts of monoethyl benzeneazophosphonic acids, with an extremely low solubility in acetonitrile, may be classified as tight ion-pair salts, the correspondingly more soluble potassium salts exist as solvated loose ion-pairs in acetonitrile solutions. The interaction of crown ether either with sodium or potassium monoethyl benzeneazophosphonates produces crown separated ion-pairs.     

Synthesis and characterization of new complexes between sodium monoalkyl benzeneazophosphonates and dibenzo-18-crown-6

A new series of crystalline complexes of sodium monoethyl ester and sodium monobutyl ester of [α-(4-benzeneazoanilino)-N-benzyl]phosphonic acid,     

Complexes of macrocyclic polyethers with some potassium monoethyl benzeneazophosphonates

Complexes of the potassium monoethyl ester of [-(4-benzeneazoanilino)-N-benzyl]phosphonic acid, [-(4-benzeneazoanilino)-N-4-hydroxybenzyl]phosphonic acid and [-(4-benzeneazoanilino)-N-4-methoxybenzyl]phosphonic acid with dibenzo- 18-crown-6 and dibenzo-24-crown-8 have been studied. The new complexes were identified and characterized on the basis of elemental and thermogravimetric analysis, conductivity measurements, and UV, IR and ¹H NMR spectra. The results obtained were compared with those obtained for the corresponding sodium monoalkyl benzeneazophosphonate complexes. It has been observed that the formation of salt complexes is controlled by a combination of factors, including the metal cation size in relation to the polyether hole, size and charge density of the anion, as well as the choice of the reaction solvent.     

Sodium and potassium benzeneazophosphonate complexes with crown ethers: Solid-state microwave synthesis, characterization and biological activity

The eco-friendly synthesis, spectroscopic (IR, MS, ¹H and ¹³C NMR) study and biological (cytostatic, antiviral) activity of sodium and potassium benzeneazophosphonate complexes, obtained by reaction in the solid state under microwave irradiation of the alkali salts of ethyl [α-(4-benzeneazoanilino)-N-benzyl]phosphonic acid and [α-(4-benzeneazoanilino)-N-4-methoxybenzyl]phosphonic acid with crown ethers containing 18-membered (dibenzo-18-crown-6 and bis(4′-di-tert-butylbenzo)-18-crown-6), 24-membered (dibenzo-24-crown-8) and 30-membered (dibenzo-30-crown-10) macrocyclic rings, have been described. The simple work-up solvent free reaction is an efficient green procedure for the formation of mononuclear crown ether complexes in which the sodium/potassium ion is bound to oxygen atoms of the macrocycle and the phosphonic acid oxygen. The free crown ethers, alkali benzeneazophosphonate salts and their complexes were evaluated for their cytostatic activity in vitro against murine leukemia L1210, murine mammary carcinoma FM3A and human T-lymphocyte CEM and MT-4 cell lines, as well as for their antiviral activity against a wide variety of DNA and RNA viruses. The investigated compounds showed no specific antiviral activity, whereas all the free crown ethers and their complexes demonstrated cytostatic activity, which was especially pronounced in the case of bis(4′-di-tert-butylbenzo)-18-crown-6 and its complexes.     

Synthesis of Dye-Labeled Lysine Derivatives

The N′-dabcyl-N ^α-(9-fluorenylmethoxy)-carbonyllysine was prepared by reaction of lysine-Cu²⁺ complex with the N-hydroxysuccinimide (HOSu) activated ester of [4-(4'-dimethylamino)phenylazo]benzoic acid (dabcyl acid) followed by treatment with EDTA and acylation with Fmoc-OSu, and the N ^α-tert-butyloxycarbonyl-N′-dabcyllysine was prepared by reaction of N ^α-tert-butyloxycarbonyllysine with dabcyl-OSu.     

New atropoisomeric alkenylphenylglycine derivatives: Synthesis of (5R*)- and (5S*)-isomers of (1R*,3aR*,4S*,11S*)-3a,5,9,11-tetramethyl-4,5-dihydro-3aH-1,4-methano[1,3]oxazolo[3,2-a]quinolin-2-one

We synthesized methyl ester of N-(1-methylbut-2-en-1-yl)-N-phenylglycine which underwent acid catalyzed aromatic amino Claisen rearrangement to provide methyl-N-[2-(1-methylbut-2-en-1-yl)phenyl]glycinate. A mixture of syn- and anti-atropisomeric methyl-N-acetyl-N-[4-methyl-2-(1-methylbut-2-en-1-yl)phenyl]glycinates was obtained either by the reaction of this ester with acetyl bromide or by the reaction of the sodium salt of N-acetyl-2-(1-methylbut-2-en-1-yl)-4-methylaniline with methyl bromoacetate. Upon saponification of the synthesized ester mixture the syn-atropisomer of N-acetyl-N-[4-methyl-2-(1-methylbut-2-en-1-yl)phenyl]glycine was isolated by fractional crystallization. Treatment of the obtained acids with acetic anhydride, ethyl chloroformate, dicyclohexylcarbodiimide or isopropenylacetate leads to compounds of 4,5-dihydro-3aH-methano[1,3]oxazolo[3,2-a]quinolin-2-one structure.     

Functional mimics of copper enzymes. Synthesis and stereochemical properties of the copper(II) complexes of a trinucleating ligand derived from l-histidine

The ligand piperazine-1,4-bis[4-(N-(1-acetoxy-3-(1-methyl-1H-imidazol-4-yl))-2-propyl)-N-(1-methyl-1H-imidazol-2-ylmethyl)aminobutyl] (PHI) was synthesized by a multistep procedure starting from N^τ-methyl-l-histidine, piperazine-1,4-bis[4-(4-oxo-4-butanoic) acid] and 1-methyl-1H-imidazole-2-carbaldehyde. This ligand has two potential tridentate, aminobis(imidazole) (A sites), and one bidentate, piperazine (B site), binding sites for metal ions and was employed for the synthesis of the binuclear [Cu₂PHI]⁴⁺ and the trinuclear [Cu₃PHI]⁶⁺ complexes, the latter of which features a coordination environment mimicking that present in the trinuclear clusters of the blue copper oxidases. For comparison purposes, the mononucleating ligand l-N^α-(1-methyl-1H-imidazol-2-ylmethyl)-N^τ-methylhistidine methyl ester (IH) and its complex [CuIH]²⁺ have been also prepared. These copper(II) model complexes are the first reported which are directly derived from chiral l-histidine residues. A detailed analysis of the UV–vis, CD and EPR spectra of the complexes has established that the Cu(II) centers bound to PHI A sites are square-pyramidal in solution, with the amino and one imidazole donor in the equatorial plane and the additional imidazole group bound axially. This arrangement implies the adoption of an unusual conformation of λ chirality by the l-histidine residue and is determined by the attempts to minimize steric interference between the substituents at the tertiary amine donor group and the histidine residue bearing the C-α substituent acetoxymethylene group of the bound PHI ligand. For the less sterically crowded secondary amine group of the bound IH ligand, the histidine C-α substituent can occupy a pseudoaxial position, so that in the complex [CuIH]²⁺ the `normal' arrangement with three equatorial nitrogen donors and δ chirality in the l-histidine chelate ring occurs.     

Synthesis of Four Enantiomers of (1-Amino-3-Hydroxypropane-1,3-Diyl)Diphosphonic Acid as Diphosphonate Analogues of 4-Hydroxyglutamic Acid

All the enantiomers of (1-amino-3-hydroxypropane-1,3-diyl)diphosphonic acid, newly design phosphonate analogues of 4-hydroxyglutamic acids, were obtained. The synthetic strategy involved Abramov reactions of diethyl (R)- and (S)-1-(N-Boc-amino)-3-oxopropylphosphonates with diethyl phosphite, separation of diastereoisomeric [1-(N-Boc-amino)-3-hydroxypropane-1,3-diyl]diphosphonates as O-protected esters, followed by their hydrolysis to the enantiomeric phosphonic acids. The absolute configuration of the enantiomeric phosphonates was established by comparing the ³¹P NMR chemical shifts of respective (S)-O-methylmandelic acid esters obtained from respective pairs of syn- and anti-[1-(N-Boc-amino)-3-hydroxypropane-1,3-diyl]diphosphonates according to the Spilling rule.     

Regioselectivity of the reaction of 4H-1,2,4-triazole-3-thiol derivatives with chloroethynylphosphonates and structure of the products

Chloroethynylphosphonates reacted with 4H-1,2,4-triazole-3-thiols in anhydrous acetonitrile to afford fused heterocyclic compounds, 6-(dialkoxyphosphoryl)-3H-thiazolo[3,2-b][1,2,4]triazol-7-ium chlorides, with high regioselectivity. The products were converted into inner salts (zwitterions) of the corresponding phosphonic acids or their monoesters with the positive charge localized on N⁷. A probable reaction mechanism implies initial formation of sulfonium ion via attack by the thionic sulfur atom on the acetylenic carbon atom linked to chlorine, followed by intramolecular cyclization involving attack on the other acetylenic carbon atom by N² of the triazole ring.     

Quantitative evaluation of the biosynthetic pathways leading to δ-aminolevulinic acid from the Shemin precursor glycine via the C5 pathway in Arthrobacter hyalinus by analysis of 13C-labeled coproporphyrinogen III biosynthesized from [2-13C]glycine, [1-13C]acetate, and [2-13C]acetate using 13C NMR spectroscopy

The biosynthetic pathways leading to δ-aminolevulinic acid (ALA) from the Shemin precursor glycine via the C5 pathway in Arthrobacter hyalinus were quantitatively evaluated by means of feeding experiments with [2-¹³C]glycine, sodium [1-¹³C]acetate, and sodium [2-¹³C]acetate, followed by analysis of the labeling patterns of coproporphyrinogen III (Copro’gen III) (biosynthesized from ALA) using ¹³C NMR spectroscopy. Two biosynthetic pathways leading to ALA from glycine via the C5 pathway were identified: i.e., transformation of glycine to l-serine catalyzed by glycine hydroxymethyltransferase, and glycine synthase-catalyzed catabolism of glycine to N ⁵,N ¹⁰-methylene-tetrahydrofolic acid (THF), which reacts with another molecule of glycine to afford l-serine. l-Serine is transformed to acetyl-CoA via pyruvic acid. Acetyl-CoA enters the tricarboxylic acid cycle, affording 2-oxoglutaric acid, which in turn is transformed to l-glutamic acid. The l-glutamic acid enters the C5 pathway, affording ALA in A. hyalinus. A ¹³C NMR spectroscopic comparison of the labeling patterns of Copro’gen III obtained after feeding of [2-¹³C]glycine, sodium [1-¹³C]acetate, and sodium [2-¹³C]acetate showed that [2-¹³C]glycine transformation and [2-¹³C]glycine catabolism in A. hyalinus proceed in the ratio of 52 and 48 %. The reaction of [2-¹³C]glycine and N ⁵,N ¹⁰-methylene-THF, that of glycine and N ⁵,N ¹⁰-[methylene-¹³C]methylene-THF generated from the [2-¹³C]glycine catabolism, and that of [2-¹³C]glycine and N ⁵,N ¹⁰-[methylene-¹³C]methylene-THF transformed the fed [2-¹³C]glycine to [1-¹³C]acetyl-CoA, [2-¹³C]acetyl-CoA, and [1,2-¹³C₂]acetyl-CoA in the ratios of 42, 37, and 21 %, respectively. These labeled acetyl-CoAs were then incorporated into ALA. Our results provide a quantitative picture of the pathways of biosynthetic transformation to ALA from glycine in A. hyalinus.     

Oxidation of Nα-protected-l-lysine by Rhodotorula graminis to produce novel chiral compounds

The chiral intermediates (S)-3,4-dihydro-1,2(2H)-pyridinedicarboxylic acid, 1-(phenylmethyl)ester [BMS 202665-01] and (S)-3,4-dihydro-1,2(2H)-pyridinedicarboxylic acid, 1,1-dimethylethyl ester [BMS 264406-01] were prepared by oxidation of Nα-carbobenzoxy-l-lysine (Nα-CBZ-l-lysine) and Nα-t-butoxycarbonyl-l-lysine (Nα-t-BOC-l-lysine), respectively, by cell suspensions of Rhodotorula graminis SC 16005.     

27-Ald-triterpenoid saponins from Adina rubella

Four new triterpenoid saponins were isolated from the roots of Adina rubella Hance. They were characterized as adinaic acid 3β-O-[α-L-rhamnopyranosyl(l→2)-β-D-glucopyranosyl(l→2)-β-D-glucurono-pyranoside-6-O-methyl ester]-28-O-β-D)-glucopyranoside, adinaic acid 3β-O-[α-L-rham-nopyranosyl(l→2)-β-D-glucopyranosyl(l→2)-β-D-glucuronopyranoside-6-O-butyl ester]-28-O-β-D-glu-copyranoside, adinaic acid 3β-O-[β-D-glucopyranosyl(l→2)-β-D-glucopyranosyl]-(28→1)-β-D-gluco-pyranosyl(l→6)-β-D-glucopyranosyl ester, 27-hydroxyursolic acid 3β-O-[α-L-rhamnopyranosyl (l→2)-β-O-glucopyranosyl(l→2)-β-D)-glucuronopyranoside-6-O-methyl ester]-28-O-β-D)-glucopyranoside. Their structures were elucidated by spectral methods, especially with the aid of 2D NMR techniques. Their complete assignments of the 1H and 13C NMR signals were carried out.     

Divergent and solvent dependent reactions of 4-ethoxycarbonyl-3-methyl-1-tert-butoxycarbonyl-1,2-diaza-1,3-diene with enamines

Starting from 1-tert-butyloxycarbonyl-3-methyl-4-ethoxycarbonyl-1,2-diaza-1,3-diene and β,β,β and α,β-substituted enamines a careful choice of solvents and temperatures allows the divergent synthesis of 5,6-dihydro-4H-pyridazines, 2-(1-N-boc-hydrazono-ethyl)-4-pyrrolidin-1-yl-but-3-enoic acid ethyl ester, and 1-amino-pyrroles. Moreover, some interesting conclusions about the mechanism(s) of the reaction have been drawn by careful analysis of products' structure and distribution. Thus, the reaction may proceed through a stereospecific [4+2] cycloaddition mechanism giving rise to 5,6-dihydro-4H-pyridazines or by simple addition or domino addition/cyclization pathways affording, respectively, 2-(1-N-boc-hydrazono-ethyl)-4-pyrrolidin-1-yl-but-3-enoic acid ethyl ester and 1-amino-pyrroles (formally the [3+2] cycloaddition product).     

Asymmetric synthesis of α-mercapto-β-amino acid derivatives: application to the synthesis of polysubstituted thiomorpholines

Tandem conjugate addition of homochiral lithium N-benzyl-N-(α-methyl-p-methoxybenzyl)amide to tert-butyl cinnamate and enolate trapping with TsS^tBu proceeds with high diastereoselectivity to give a homochiral anti-α-tert-butylthio-β-amino ester. Stepwise deprotection gives the corresponding free α-tert-butylthio-β-amino acid without epimerisation. Tandem conjugate addition of homochiral lithium N-allyl-N-(α-methylbenzyl)amide to tert-butyl cinnamate and enolate trapping with TsS^tBu followed by conversion of the S-tert-butyl group to a disulphide, and reduction with Lalancette’s reagent generates polysubstituted thiomorpholine derivatives.     

Rapid asymmetric synthesis of amino acids via NiII complexes based on new fluorine containing chiral auxiliaries

New fluorine-containing chiral auxiliaries (S)-N-(2-benzoylphenyl)-1-(2-fluorobenzyl)-, (S)-N-(2-benzoylphenyl)-1-(3-fluorobenzyl)-, and (S)-N-(2-benzoylphenyl)-1-(4-fluorobenzyl)-pyrrolidine-2-carboxamide and their Ni^II complexes of Schiff bases with glycine and alanine have been synthesized. The greater efficiency of the complexes in terms of faster reaction rates and stereoselectivities in the asymmetric synthesis of (S)-α-amino acids has also been demonstrated.     

Synthesis of novel chiral NiII complexes of dehydroalanine Schiff bases and their reactivity in asymmetric nucleophilic addition reactions. Novel synthesis of (S)-2-carboxypiperazine

New chiral Ni^II complexes of Schiff bases of dehydroalanine with modified chiral auxiliaries (S)-2-N-[N′-(3,4-dichlorobenzyl)prolyl]aminobenzophenone (3,4-DCBPB), (S)-2-N-[N′-(3,4-dimethylbenzyl)prolyl]aminobenzophenone (3,4-DMBPB), (S)-2-N-[N′-(2-chlorobenzyl)prolyl]aminobenzophenone (2-CBPB), and (S)-2-N-[N′-(2-fluorobenzyl)prolyl]-aminobenzophenone (2-FBPB) have been synthesized. Asymmetric Michael addition reactions of primary and secondary amines and thiols to the dehydroalanine moieties of the complexes were studied. (S)-2-FBPB was found to be the best chiral auxiliary in terms of both selectivity of the reactions (de ～92–96%) and reactivity of the complexes. A novel synthetic route toward (S)-2-carboxypiperazine was developed based on the auxiliary.     

Coordination properties of some nickel(II) monophosphono dipeptides species in aqueous solution: The role of phosphonic oxygen in complex stabilization and ligand-fields analysis

Equilibrium studies on the nickel(II) complexes of oxygen and nitrogen donor ligand (monophosphono dipeptides: 1- (N-l-leucylamino)methylphosphonic acid – Leu-Gly(P), and a thioether sulfur donor ligands (monophosphono dipeptides: 1-N-(glycyloamino)-2-(S-benzylthio)ethanephosphonic acid – Gly-(Bz)Cys(P), d(−) and Gly-(Bz)Cys(P), d(+) were performed by potentiometric titration and NIR–Vis spectroscopy. Additionally, the ligand-field parameters (CFM/AOM) were estimated and discussed in the tetragonal distortion framework. The lowest tetragonal distortion was observed in the case of the [NiHL] species, whereas the strongest in the case of [NiL₂] species. In the latter species the ligand-field analysis confirms the coordination of the deprotonated phosphonic groups to the metal ions in both axial positions. In the case of nickel(II) complexes with Gly-(Bz)Cys(P), d(−) or Gly-(Bz)Cys(P), d(+) additional interaction between sulfur donor atom and nickel(II) was suggested.     

Electrospray Ionization Mass Spectrometry of Palladium(II) Quinolinylaminophosphonate Complexes

The mass spectrometric behavior of palladium(II) halide complexes of three types of quinolinylaminophosphonates, diethyl and dibutyl esters of [α-anilino-(quinolin-2-yl)methyl]phosphonic (L1, L2), [α-anilino-(quinolin-3-yl)methyl]phosphonic (L3, L4), and [α-(quinolin-3-ylamino)-N-benzyl]phosphonic acid (L5, L6), was investigated under positive ion electrospray ionization conditions. Each type of ligand forms complexes with different metal–ligand interactions. Mononuclear dihalide adducts cis-[Pd(L1/L2)X₂] (1–4) and trans-[Pd(L3/L4)₂X₂] (5–8) as well as dinuclear tetrahalide complexes [Pd₂(L5/L6)₃X₄] (9–12) (X = Cl, Br) are formed by metal bonding either through the quinoline or both the quinoline and amino nitrogen atoms. The sodiated molecule [M + Na]⁺ is observed in the mass spectra of all the complexes, and its abundance as well as the fragmentation pathway depend on the type of the complex. In the cis complexes (1–4) the initial decomposition goes under two fragmentation routes: those in which the sodium molecular adduct sequentially loses halides HX/NaX and those in which this loss is in the competition with the loss of dialkyl phosphite. The predominant pathways for decomposition of trans dihalide (5–8) and tetrahalide (9–12) complexes include three competitive reactions; the loss of halides, dialkyl phosphites and the intact phosphonate ligand molecule and its fragments formed by ester dissociation or complete loss of the phosphonate ester moiety. A series of acetonitrile adducts and cluster ions derived from dimolecular clusters [2M + Na]⁺ were also detected. The most important fragmentation patterns are rationalized and supported by the MS ⁿ studies.     

季胺基修饰的Salen配合物的合成及性质

采用季胺基取代的水杨醛(由2,4-二羟基水杨醛、1,2-二溴乙烷、高氯酸钠等为原料合成)合成了两个新型Salen配体N,N'-二{4-[[2-(三甲胺基)乙基]氧化]水杨醛}-邻苯二胺二高氯酸盐(L¹), N-(2-羟基-5-甲基二苯甲基)-N'-{4-[[2-(三甲胺基)乙基]氧化]水杨醛}-邻苯二胺高氯酸盐(L²), 并进一步合成了8个新型Salen金属配合物[ZnL¹, NiL¹, CuL¹, ZnL², NiL², CuL², MnL², CoL²]. 用¹H NMR, ¹³C NMR, FT-IR, UV-vis, MS对配体和配合物进行了表征, 测定了金属配合物的水溶性及在水中的摩尔电导率. 结果表明, 与相应母体配合物的水溶性比较, 含有季胺基修饰的Salen金属配合物的水溶性有了较大提高.     

Alkali Metal Complexation. Binding Properties of cone and partial-cone Calix[4]arenes Bearing a Mixed (O 2 , O 2 ') Donor Set (O = Phosphine Oxide; O ' = Amide or Ester)

The stability constants of alkali metal complexes obtained from the followingO-substituted calix[4]arenes were determined by UV/Vis spectroscopy inmethanol at 20°C: 5,11,17,23-tetra-tert-butyl-25,27-bis(diethylcarbamoylmethoxy)-26,28-bis(diphenylphosphinoylmethoxy)calix[4]arene(cone-1), 25,27-syn-26,28-anti-5,11,17,23-tetra-tert-butyl-25,27-bis(diethylcarbamoylmethoxy)-26,28-bis(diphenylphosphinoylmethoxy)calix[4]arene (paco-1),5,11,17,23-tetra-tert-butyl-25,27-diethoxycarbonylmethoxy-26,28-bis(diphenylphosphinoylmethoxy)calix[4]arene(cone-2) and25,27-syn-26,28-anti-5,11,17,23-tetra-tert-butyl-25,27-diethoxycarbonylmethoxy-26,28-bis(diphenylphosphinoylmethoxy)calix[4]arene(paco-2). All ligands form 1:1 complexes with alkali metal cations. The amide-containing calixarenes were found to be more efficient for alkali metalcomplexation than those bearing ester substituents. While sodium ions are selectivelycomplexed by the two mixed amide-(phosphine oxide) calixarenes, the twoester-containing isomers cone-2 and paco-2 turned out to be selective towards potassium and rubidium ions, respectively. With allfour ligands the lowest stability constants were found for the lithium andcesium ions.