Pentamidine Analogs: Syntheses, Structures in Solid State by 13C CP/MAS NMR Spectroscopy, and X-Ray Crystallography and their Preliminary Biological Screening Against Human Cancer

The synthesis of four new 1,5-bis(4-amidinophenoxy)-3-oxapentane analogs is described. The structures of the obtained bis-amidines and bis-nitriles in the solid state are evaluated on the basis of ¹³C CP/MAS NMR spectra and theoretical calculations at DFT level. A single crystal X-ray diffraction structure is presented for 1,5-bis(4-amidinophenoxy)-3-oxapentane. A preliminary anticancer assay against three cell lines is also given.     

Unusual heterocyclization of chalcone podands with 3-amino-1,2,4-triazole

A new type of intramolecular cyclization of 1,5-bis[2-(E-3-oxo-3-phenylprop-1-enyl)-phenoxy]-3-oxapentane with 3-aminotriazole promoted by potassium ions was discovered. A cascade mechanism for the formation of crownophane with 4,7-dihydro[1,2,4]triazolo[1,5-a]-pyrimidine fragment was suggested. Effects of oligooxyethylene fragment of the chalcone podand and acid-base catalysis on the selectivity of the cyclocondensation processes and degree of oxidation of triazolopyrimidine fragments were studied. The product structures were confirmed by IR, ¹H and ¹³C NMR spectroscopy and X-ray diffraction study.     

Ion-selective and complexation properties, vibrational spectra, and crystal and molecular structure of 1,5-bis[2-(hydroxyethoxyphosphoryl)phenoxy]-3-oxapentane

The ion-selective properties of 1,5-bis[2-(hydroxyethoxyphosphoryl)phenoxy]-3-oxapentane H₂R² have been described. The molecular and crystal structure of H₂R² has been determined by powder X-ray crystallography and IR spectroscopy. The molecule has the twofold symmetry axis, orthorhombic crystal system, space group Pbcn, a = 16.830(2) ?, b = 8.866(15) ?, c = 15.7190(2) ?, V = 2346.1(6) ?³, Z = 4. A new CuR² · 2H₂O complex has been synthesized and characterized.     

Complexing and ion selective properties of some acid type phosphoryl podands. The crystal and molecular structures of 1,5-bis(2-dihydroxyphosphoryl-4-ethylphenoxy)-3-oxapentane dihydrate [(HO)2(O)P(C6H3CH2CH3)(OCH2CH2)2O (C6H3CH2CH3)P(O)(OH)2] · 2H2O

The synthesis of 1,5-bis(2-dihydroxyphosphoryl-4-ethylphenoxy)-3-oxapentane [(HO)₂(O)P(C₆H₃CH₂CH₃)(OCH₂CH₂)₂O(C₆H₃CH₂CH₃)P(O)(OH)₂] (H₄K²) and single crystal X-ray diffraction study of H₄K² · 2H₂O (I) are described. The crystals are orthorhombic, a = 33.291(4) Å, b = 8.9374(10) Å, c = 8.1021(9) Å, V = 2410.6(5) ų, Z = 4, space group Cmc2₁, R = 0.0484 for 2566 reflections with I > 2σ(I). In I, the molecules of H₄K² are hydrogen-bonded to two crystallographically independent H₂O molecules to give neutral conglomerates H₄K² · 2H₂O. The electroanalytical characteristics of poly(vinyl chloride) membranes based on H₄K² were tested. Cu²⁺ and Zn²⁺ complexes with H₄K² and Er³⁺, Nd³⁺, and complexes with H₄K², 1,5-bis[2-(dihydroxyphosphoryl-4-methoxy)phenoxy]-3-oxapentane, 1,5-bis[2-(dihydroxyphosphinyl)phenoxy]-3-oxapentane, and 1,8-bis[2-(dihydroxyphosphinyl)phenoxy]-3,6-dioxaoctane were prepared.     

Facile synthesis of macrocyclic tetrazoles by regioselective cycloalkylation of bistetrazoles with 2,5-dimethylhexane-2,5-diol in perchloric acid

Alkylation of 1,5-bis(tetrazol-5-yl)-3-oxapentane with 2,5-dimethylhexane-2,5-diol in 65% aqueous perchloric acid was found to proceed selectively on the N2 atoms of both tetrazole rings generating a 15-membered macrocycle with tetrazol-2,5-diyl moieties incorporated (yield ca. 80%). Under analogous alkylation conditions 1,5-bis(1-methyltetrazol-5-yl)-3-oxapentane undergoes quaternization resulting in a macrocyclic tetrazolium perchlorate containing two 1-methyltetrazolium-3,5-diyl units linked by 3-oxapentane-1,5-diyl and 2,5-dimethylhexane-2,5-diyl bridges. Crystal structures of the macrocyclic compounds obtained, determined by single crystal X-ray analysis, are described.     

Syntheses of diethyleneoxy bridged cryptophanes and their complexing abilities with alkali metal and alkylammonium cations

Abstract

The anti- and syn-diethyleneoxy bridged cryptophanes (3a and 3b) were prepared by the direct trimerization of 1,5-bis[(4-hydroxymethyl)-2-methoxyphenoxy]-3-oxapentane, which was obtained by the reaction of diethyleneglycol ditosylate with vanillyl alcohol and/or by stepwise methods from vanillyl alcohol. The syn isomer (3b) showed highly selective complexing abilities for cesium, and the tetraethylammonium and triethylmethylammonium cations as compared with those of the anti isomer (3a).     

New 1,2,4-triazine-containing podands: synthesis and properties

A method of one-step C-C coupling of 1,5-bis(2,6-dimethylphenoxy)-3-oxapentane (1a) and 1,8-bis(2,6-dimethylphenoxy)-3,6-dioxaoctane (1b) with 3-methylthio- (2) and 3-amino-1,2,4-triazine (3) and 3-aryl-1,2,4-triazin-5-one (6-8) has been described. The reaction of compounds 1a,b with compounds 2 and 3 in the presence of trifluoroacetic acid results in the addition of the dimethylphenoxy group to the unsubstituted C(5) carbon atom of the triazine ring. The reactions of triazinones 6-8 with compounds 1a,b in a mixture of trifluoroacetic acid and organic anhydrides are accompanied by the acylation of the nitrogen atom adjacent to the reaction center and affords bis[(3-R-1-acyl-5-oxo-1,4,5,6-tetrahydro-1,2,4-triazin-6-yl)-2,6-dimethylphenoxy]-3-oxapentane or -3,6-dioxaoctane. The obtained adducts can smoothly be oxidized under mild conditions to form more stable products of nucleophilic hydrogen substitution in the triazine ring. The extraction and transport of Ca²⁺ and Mg²⁺ cations through an organic membrane by the compounds synthesized are discussed.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2210–2215, October, 2004.     

Synthesis and characterization of new crown-type compounds with 4-pyrone Units

We report here the syntheses and characterization of new crown-type compounds 8 and 9 incorporated with one and two 4-pyrone units. The reaction of compound 3 with 1,5-bis(2-hydroxyphenoxy)-3-oxapentane or catechol gave the desired molecules 8 and 9 in 65% and 25% yields, respectively. Compound 3 resulted from 1 by Wohl-Ziegler bromination in small amounts and could be separated from five bromination by-products by column chromatography. For example, 8 binds K⁺ and a pyrylium salt 11 (single crystal X-ray structure analysis) can also be prepared starting from 3 by treatment of the latter with perchloric acid in the presence of acetonitrile.     

IR spectroscopy and single crystal X-ray diffraction study of 1,2-bis(2-aminophenoxy)-ethane, 1,5-bis(2-aminophenoxy)-3-oxapentane,and 1,8-bis(2-aminophenoxy)-3,6-dioxaoctane

Vibrational spectra of 1,2-bis(2-aminophenoxy)-ethane, 1,5-bis(2-aminophenoxy)-3-oxapentane, and 1,8-bis(2-aminophenoxy)-3,6-dioxaoctane–podands, different in the length of oxyethylene fragments, are measured and their single crystal X-ray diffraction analysis is performed. It is demonstrated that the strength of intermolecular hydrogen bonds (IMHB) with the participation of NH groups increases with the elongation of the oxyethylene spacer. According to the XRD data for 1,2-bis(2-aminophenoxy)-ethane, the weakest hydrogen bonds are characteristic. From the IR spectra, important intermolecular hydrogen bonds are typical of 1,8-bis(2-aminophenoxy)-3,6-dioxaoctane having the longest oxyethylene fragment.     

Extraction properties of organic salts of acidic phosphoryl podands and trioctylamine with respect to cesium

The extraction ability of the organic salt of acidic phosphoryl podand (1,5-bis(o-(hydroxyethoxyphosphoryl)phenoxy)-3-oxapentane) and trioctylamine with respect to cesium in nitric acid and carbonate media is investigated. The extraction ability of the organic salts of acidic phosphoryl podand and trioctylamine are compared to those of dibenzo-18-crown-6 and di-tert-butyldicyclohexano-18-crown-6. It is shown that organic salts of this type have a significant advantage in the extraction of cesium from nitric acid and carbonate solutions.     

Photoinduced template synthesis of cyclobutane-containing crown ether

The photoinitiated [2+2]-cycloaddition of 1,5-bis[2-(3-phenyl-3-oxoprop-1-en-1-yl)phenoxy]-3-oxapentane in solution was studied. In the presence of potassium cations, the reaction is intramolecular and gives crown ether containing the γ-truxin-type cyclobutane fragment (anti, head-to-head) as the major product. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 204–206, January, 2008.     

Lithium 1,5-bis[2-dioxyphosphinyl)phenoxy]-3-oxapentane hydrate: Synthesis,vibrational spectra,and crystal structure

The complex [Li(H₃L²)(H₂O)] _n (I), where H₄L² is 1,5-bis[2-(dioxyphosphinyl)phenoxy]-3-oxapentane, is synthesized. Its crystal and molecular structures are determined by X-ray diffraction analysis and vibrational spectroscopy. Complex I is an isolated chain polymer in which the Li⁺ cations bind anions (H₃L²)^? of the bridging ligand. The crystals are orthorhombic: a = 8.1860(3) Å, b = 9.9093(4) Å, c = 23.6293(8) Å, V = 1916.75(12) ų, Z = 4, space group Pna2 ₁. The framework of the polymer chain is stabilized by hydrogen bonds between two hydrogen atoms of the coordinated water molecule and two oxygen atoms of the ether and phosphone groups.     

Studies on the synthesis and properties of open-chain and macrocyclic crown compounds

Eight new open-chain crown compounds (1–8) and two new macrocyclic crown ethers (9 and10) were synthesized from 1,5-bis(2-aminophenoxy)-3-oxapentane (15) and 1,8-bis(2-aminophenoxy)-3,6-dioxaoctane (16) which were prepared by the catalytic hydrogenation of the corresponding bis(2-nitrophenoxy) derivatives13 and14. The fluorescent property investigation of two open-chain crown ethers (7 and8) indicated that they exhibit complexing effects on Ag⁺ and Mn²⁺ cations and can be used as fluorescent reagents for the microanalysis of the metal cations. The pyrolysis kinetics measurement for compounds5 and6 in nitrogen and air was carried out, and their reaction orders and activation energy were obtained. They are one-step and two-step pyrolysis reactions in nitrogen and air, respectively.     

Synthesis,characterization, and antioxidant activity of heterocyclic Schiff bases

Schiff base derivatives have gained great importance due to revealing a great number of biological properties. Schiff bases were synthesized by treatment of 4-amino-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one ( 1 ) with various aldehydes in methanol at reflux. In addition, diamine was reacted with an aldehyde to yield the corresponding Schiff bases. The structures of synthesized Schiff bases were elucidated by spectroscopic methods such as microanalysis, ¹H-NMR, ¹³C-NMR, and FTIR. Antioxidant activities of synthesized Schiff bases were carried out using different antioxidant assays such as 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH^•) scavenging, 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging, and reducing power activity. (E)-4-((1H-indol-3-yl)methyleneamino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one ( 3 ), (E)-1,5-dimethyl-4-((2-methyl-1H-indol-3-yl)methyleneamino)-2-phenyl-1H-pyrazol-3(2H)-one ( 5 ), (E)-1,5-dimethyl-2-phenyl-4-(thiophen-2-ylmethyleneamino)-1H-pyrazol-3(2H)-one ( 7 ), (E)-1,5-dimethyl-2-phenyl-4-(quinolin-2-ylmethyleneamino)-1H-pyrazol-3(2H)-one ( 9 ), (1S,2S,N1,N2)-N1,N2-bis((1H-indol-3-yl)methylene)cyclohexane-1,2-diamine ( 11 ), and (1S,2S,N1,N2)-N1,N2-bis((2-methyl-1H-indol-3-yl)methylene)cyclohexane-1,2-diamine ( 12 ) were synthesized in high yields. Compound 5 displayed a good ABTS^•+ activity. Compound 3 revealed the outstanding activity in all assays. Compound 7 has the best-reducing power ability in comparison to other synthesized compounds. Although compounds 5, 11, 12 are new, compounds 3, 7, 9 are known. Due to revealing a good antioxidant activity, the synthesized compounds ( 3, 5, 7 ) have the potential to be used as synthetic antioxidant agents.     

Complexes of Li,Na, Ba,and Er with 1,5-Bis[2-(diphenylphosphinyl)phenoxy]-3-oxapentane

Complexes of Li, Na, Ba, and Er with 1,5-bis[2-(diphenylphosphinyl)phenoxy]-3-oxapentane (L) were synthesized and their IR spectra were examined. Some of the complexes were studied by thermogravimetric methods. The structures of the synthesized compounds were suggested on the basis of their spectra and previous X-ray studies. In Ba and Er complexes, L was found to be coordinated to the metal atom through the phosphoryl oxygen atoms, whereas in Li and Na complexes, both the phosphoryl and anisole oxygen atoms are involved in coordination. The structures of complexes was determined to depend on the nature of a metal and acidoligand and on the ratio of reagents used in the synthesis.     

Stereochemistry of Macrocyclization of cis-4-Cyclohexene-1,2-dicarboxylic Acid with Dihalogen Derivatives

Stereochemistry of [2+2]- and [1+1]-macrocylization of cis-4-cyclohexene-1,2-dicarboxylic acid with 1,2-dibromoethane, 1,3-dichloro-2-propanol, and 1,5-dichloro-3-oxapentane was studied. The reaction of cis-4-cyclohexene-1,2-dicarboxylic acid with 1,2-dibromoethane according to the [2+2]-cyclization scheme gave a mixture of stereoisomeric macroheterocycles with cis,syn,cis- and cis,anti,cis-junction of the polyether and cyclohexene rings. In the reaction of cis-4-cyclohexene-1,2-dicarboxylic acid with 1,5-dichloro-3-oxapentane, a mixture of crown compounds with cis,anti,cis- and cis-junction of the polyether and cyclohexene rings was obtained. The structure of the products was established on the basis of their chemical transformations and spectral data.     

Synthesis, vibrational spectra, and crystal and molecular structure of copper 1,5-bis[2-(dihydroxyphosphinyl)phenoxy]-3-oxapentane dihydrate [Cu(H2L2)(H2O)2]

A new complex Cu(H₂L²)(H₂O)₂] (I), where H₄L² is 1,5-bis[2-(dihydroxyphosphinyl)phenoxy]-3-oxapentane, has been synthesized and characterized. Its molecular and crystal structure has been determined by X-ray crystallography and vibrational spectroscopy. In mononuclear complex I, the copper(II) cation is in a distorted square-planar environment of two water oxygen atoms and two oxygen atoms of the chelating dianion (H₂L²)^2?. The crystals are orthorhombic, space group Cmc2₁, a = 25.909(5) ?, b = 9.1500(18) ?, c = 8.5600(17) ?, V = 2029.3(7) ?³, Z = 4, ??_calc = 1.688 g cm^?3, ?? = 1.292 cm^?1; 3107 measured reflections, 1174 reflections with I > 2.0??(I), R _int = 0.0600, GOOF = 1.413, R ₁ (I > 2??(I)) = 0.0812, wR ₂ (I > 2??(I)) = 0.2145.     

Acyclic analogs of nucleosides. Synthesis of 1,5-dihydroxy-3-oxa-2-pentyl derivatives of nucleic bases

A convenient method for the synthesis of 1,5-dihydroxy-3-oxa-2-pentyl derivatives of nucleic bases, which consists in the condensation of trimethylsilyl derivatives of nucleic bases with 1,2,5-triacetoxy-3-oxapentane in the presence of SnCl₄, is proposed. Optically active derivatives — (R)- and (S)-1-(1,5-dihydroxy-3-oxa-2-pentyl)uracil, respectively — were obtained by periodate oxidation of -L- and -D-arabinopyranosyluracil.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 223–228, February, 1988.     

X-ray diffraction study of 1,5-bis-(4′,4′,4′-trifluoro-1′-methyl-3′-oxo-but-1′-enylamino)-3-oxapentane

Specific features of the molecular and crystal structures of 1,5-bis-(4′,4′,4′-trifluoro-1′-methyl-3′-oxo-but-1′-enylamino)-3-oxapentane are determined by single crystal XRD.     

Synthesis of macroheterocyclic analogs of dibenzocrown ethers. 5. 16- and 17-Membered oxaazacrown ethers

Macrocyclic diamides are synthesized by condensation of 1,5-bis(2-aminophenyl)-1,5-dioxapentane and 1,6-bis(2-aminophenyl)-1,6-dioxahexane with the dichlorides of glutaric, diglycolic, thiodiglycolic, and N-tosyliminodiacetic acids under high dilution conditions. Reduction with diborane gives the 16- and 17-membered dibenzodiazacrown ethers. The structure of the compounds synthesized is confirmed by IR,NMR (¹H and ¹³C), and mass spectral data.For Communication 4, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 691–696, May, 1990.