Conformational analysis and electronic structure calculations of S-1,2-bis(2-dibutenoyl)glycerol and S-1,2-bis(2,4-hexadienoyl)glycerol,two analogues of 1,2-bis(2,4-octadecadienoyl)-sn-glycero-3-phosphorylcholine

As a model for 1,2-bis(2,4-octadecadienoyl)-sn-glycero-3-phosphorylcholine, a doubly unsaturated membrane-forming lipid molecule, force-field (MMP2) calculations were performed on S-1,2-bis(2-dibutenoyl)glycerol, and CNDO/S-calculations 2

1 CNDO: Complete neglect of differential overlap, a semi-empirical quantum-mechanical method.

on the derived minimum-energy conformations of S-1,2-bis(2,4-hexadienoyl)glycerol. The energy hypersurface especially with respect to the dihedral angles along the C(1)-C(2) and the two C O ester bonds was explored and the rotational strength as a function of these angles was calculated. The two gauche-forms were found to be most stable, with a slight preference for the g⁻-form. The experimental circular dichroism data obtained for 1,2-bis(2,4-hexadienoyl)-sn-glycero-3-phosphorylcholine, the corresponding phosphorylcholine, indicate a dynamic equilibrium between two forms of opposite chirality possibly involving the g⁺-and the g⁻-forms.     

Identification of O-Isobutyl S-(2-Diethylaminoethyl) Methylthiophosphonate Chemical Neutralization Products in Bitumen–Salt Matrices

Products of the chemical neutralization of O-isobutyl S-(2-diethylaminoethyl) methylthiophosphonate, a VX Group warfare agent, in bitumen–salt matrices were studied by gas chromatography–mass spectrometry. Forty-four compounds were characterized by their electron impact ionization mass spectra and gas chromatographic retention indices on standard nonpolar polydimethylsiloxane phases; seven of these compounds were determined as derivatives. The structures of 26 compounds were identified, including structures of 24 O-isobutyl S-(2-diethylaminoethyl) methylthiophosphonate neutralization products. To solve this problem, chromatographic retention indices of unknown compounds were evaluated using reference data for their structural analogues. Partition coefficients in the binary heterophase hexane–octanol system were determined for the major components.     

Synthesis of poly[S-(2–9′-acridinylethyl)-L-cysteine] and its TCNQ salt

Poly[S-(2–9′-acridinylethyl)-L -cysteine] ( 5 ) was synthesized by the N-carboxy anhydride procedure. It was converted to the trifluoroacetic acid salt ( 6 ), which was treated with LiTCNQ in methanol to give the TCNQ anion radical salt ( 7 ). 7 showed electrical conductivity of 10^?8 S/cm at 295 K.     

Absolute Conformation and Configuration of (2S, 3S)-3-Acetoxy-5-(dimethylaminoethyl)-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one Chloride (Dilthiazem Hydrochloride)

Resolution of racemic cis-3-(2-aminophenylthio)-2-hydroxy-3-(4-methoxyphenyl) propionic acid ( 2 ) via the cinchonidine salt 3 , and brucine salt 4 , isolation of the calcium salts (+)- and (?)- 5 , as well as their cyclization to enantiomeric 1,5-benzothiazepines (+)- and (?)- 1 , are described. X-Ray single-crystal analysis reveals (2S, 3S) absolute configuration of (+)- 1 on the basis of tentative comparison of CD data with those for the 1,4-benzodiazepine derivative (+)- 8 of known absolute configuration.     

Kinetics and Quantum-Chemical Modelling of the Arylation of Aniline and Piperidine by N-Polynitroarylpyridinium Salts

N-Picryl-4-[4-(dimethylamino)styryl]pyridinium salt anions catalyze S _NAr reactions with aniline in acetonitrile. The anion activity increases with increasing basicity. A stepwise substitution mechanism involving the salt anions is confirmed by MNDOd and PM3 semiempirical calculations of the change in free energy of the individual reaction steps of N-polynitrophenylpyridinium chlorides with aniline and piperidine.     

Potential propelling and rotating functions of propeller-type complexes. I. Preparation and molecular dynamics simulation of tris(S-2,3-diaminopropionato)cobalt(III)

Four optically active geometric isomers of tris(S-2,3-diaminopropionato)cobalt(III) were prepared and separated by ion-exchange column chromatography on SP-Sephadex (C-25). The identification of the four diastereomers is based on the elution order of the complexes, elemental analysis, electronic spectra, circular dichroism spectra, ¹³C NMR spectra, X-ray structure analysis and comparison of these properties with those of analogous series consisting of three isomers of the bis(S-2,3-diaminopropionato)cobalt(III) ion. Structure optimization and molecular dynamics (MD) simulation of the system, consisting of the propeller-type complex fac-tris(S-2,3-diaminopropionato)cobalt(III) and 240 water molecules, were performed using AMBER 6. The results of the MD simulation suggest that distinct propelling and rotating behavior can be obtained in this complex in aqueous solution.     

Reaction of Elemental Phosphorus (P4) with Thiophenol in the Presence of Amines

Elemantal phosphorus (P₄) reacts with thiophenol and amines at elevated temperature in acetonitrile to give ammonium or acetimidamidium S,S-diphenyl phosphorodithioates, depending on the nature of the amine. Analogous salts were isolated in the reaction of triphenyl phosphorotrithioite with thiophenol and corresponding amines in acetonitrile. The molecular and crystal structures of the acetimidamidium salt was confirmed by X-ray diffraction. With two different types of intermolecular interactions taken into account, a 1D supramolecular structure formed by infinite cylinders, rather that 0D structures, dimers of anion-cation pairs formed by classical hydrogen bonds exclusively, was obtained. S,S,S-Triphenyl phosphorotrithioate is formed by the reactions of P₄ with thiophenol and a catalytic amount of an amine or in the presence of diphenyl disulfide.__________Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 6, 2005, pp. 886–892.Original Russian Text Copyright © 2005 by Badeeva, Batyeva, Gubaidullin, Litvinov, Sinyashin.     

Synthesis of 1-substituted (R,S)-8-(2-methoxy-5-methylphenyl)-3,3,9-trimethyl-2-azaspiro[4.5]deca-1,7-dien-6-ones

Reactions between p-methylanisole, isobutyraldehyde, and nitriles (acetonitrile, methyl thiocyanate, or ethyl cyanoacetate) in conc. H₂SO₄ yield 1-substituted (R,S)-8-(2-methoxy-5-methylphenyl)-3,3,9-trimethyl-2-azaspiro[4.5]deca-1,7-dien-6-ones.     

Synthesis of S-5-pyrrolo[2,3-b]pyridinemethyl and S-5- and S-6-pyrrolo[2,3-d]pyridinemethyl derivatives of 5′-deoxy-5′-thioadenosine

Reaction of 5-dimethylaminomethylpyrrolo[2,3-b]pyridine methiodide or 5-dimethylaminomethylpyrrolo[2,3-d]pyrimidin-4-one methiodide with 5′-deoxy-5′-S-thioacetyl-N⁶-formyl-2′,3′-O-isopropylideneadenosine in ethanolic sodium hydroxide solution, followed by deprotection of the resulting thioether in 80% formic acid, afforded 5′-deoxy-5′-(5-pyrrolo[2,3-b]pyridinemethylthio)adenosine or 5′-deoxy-5′-[5-(pyrrolo[2,3-d]pyrimidin-4-one)methylthio]adenosine, respectively. Similarly, the metiodide salt of the iso-gramine analog, 2-amino-6-dimethylaminomethylpyrrolo[2,3-d]pyrimidin-4-one afforded 5′-deoxy-5′-[6-(2-aminopyrrolo[2,3-d]pyrimidin-4-one)methylthio]adenosine.     

Highly Enantiopure (tert-Butyldiphenylsilyloxymethyl)Oxiranes from Barium Carbonate

The synthesis of (2R)-(tert-butyldiphenylsilyloxymethyl)oxirane and the (2S)-enantiomer from barium carbonate was developed. Methyl glycolate or the hydroxamate analog was prepared and in turn reacted with (S)-(-)-methyl p-tolylsulfoxide or the (R)-enantiomer to make β-keto sulfoxides. From the sulfoxides, we made the diastereoisomeric alcohols in a highly selective sulfoxide group directed hydride reduction, and a Pummerer rearrangement reaction followed by deprotection yielded the enantiomeric diols. (2R)-(tert-Butyldiphenylsilyloxymethyl)oxirane and its (2S)-enantiomer were derived from these diols in an overall yield of 56% from barium carbonate. This method was developed to provide a convenient access to isotope-labeled analogs of these compounds.     

An economic,practical access to enantiopure 1,1′-bi-2-naphthols: enantioselective complexation of threo-(1S,2S)-N-benzyl-N,N-dimethyl[1,3-dihydroxy-1-(4′-nitrophenyl)]-2-propylammonium chloride

An economic, convenient access to enantiopure (R)- and (S)-1,1′-bi-2-naphthol (BINOL) has been discovered. Racemic 1,1′-bi-2-naphthol was reacted with threo-(1S,2S)-N-benzyl-N,N-dimethyl-[1,3-dihydroxyl-1-(4′-nitrophenyl)]-2-propylammonium chloride (BDDNPAC) in water-containing acetonitrile under reflux until the solid dissolved completely, and then cooled to ambient temperature to isolate a yellow-greenish crystal consisting of BDDNPAC, (S)-BINOL, and water, which was analyzed by single crystal X-ray structural analysis. Enantiopure (S)- and (R)-1,1′-bi-2-naphthols were obtained in high yield after decomposition of the colored crystalline complex and evaporation of the acetonitrile solution removed from the complex crystals and successive crystallization. The chiral quaternary ammonium salt BDDNPAC can be recovered and reused without any decrease in efficiency.     

Chirale Synthesebausteine durch Kolbe-Elektrolyse enantiomerenreiner β-Hydroxy-carbonsäurederivate. (R)- und (S)-Methyl-sowie (R)-Trifluormethyl-γ-butyrolactone und -δ-valerolactone

Chiral Building Blocks for Syntheses by Kolbe Electrolysis of Enantiomerically Pure β-Hydroxybutyric-Acid Derivatives. (R)- and (S)-Methyl-, and (R)-Trifluoromethyl-γ-butyrolactones, and -δ-valerolactones The coupling of chiral, non-racemic R* groups by Kolbe electrolysis of carboxylic acids R*COOH is used to prepare compounds with a 1.4- and 1.5-distance of the functional groups. The suitably protected β-hydroxycarboxylic acids (R)- or (S)-3-hydroxybutyric acid, (R)-4,4,4-trifluoro-3-hydroxybutyric acid (as acetates; see 1 – 6 ), and (S)-malic acid (as (2S,5S)-2-(tert-butyl)-5-oxo-1,3-dioxolan-4-acetic acid; see 7 ) are decarboxylatively dimerized or ‘codimerized’ with 2-methylpropanoic acid, with 4-(formylamino)butyric acid, and with monomethyl malonate and succinate. The products formed are derivatives of (R,R)-1,1,1,6,6,6-hexafluoro-2,5-hexanediol (see 8 ), of (R)-5,5,5-trifluoro-4-hydroxypentanoic acid (see 9,10 ), of (R)- and (S)-5-hydroxyhexanoic acid (see 11 ) and its trifluoro analogue (see 12, 13 ), of (S)-2-hydroxy- and (S,S)-2,5-dihydroxyadipic acid (see 23, 20 ), of (S)-2-hydroxy-4-methylpentanoic acid (‘OH-leucine’, see 21 ), and of (S)-2-hydroxy-6-aminohexanoic acid (‘OH-lysine’, see 22 ). Some of these products are further converted to CH₃- or CF₃-substituted γ- and δ-lactones of (R)- or (S)-configuration ( 14 , 16 – 19 ), or to an enantiomerically pure derivative of (R)-1-hydroxy-2-oxocyclopentane-1-carboxylic acid (see 24 ). Possible uses of these new chiral building blocks for the synthesis of natural products and their CF₃ analogues (brefeldin, sulcatol, zearalenone) are discussed. The olfactory properties of (R)- and (S)-δ-caprolactone ( 18 ) are compared with those of (R)-6,6,6-trifluoro-δ-caprolactone ( 19 ).     

Synthesis of a S-(Carboxymethyl)cysteine Analog of (L-2-Amino-6-adipyl)-L-cysteinyl-D-valine and its Cell Free Biosynthetic Conversion into 6-[2-(D-2-Amino-2-carboxyethyl)thio) acetamido]penicillanic Acid

A new tripeptide (dimer), bis[(L -cysteine-S-acetyl)-L -hemicystinyl(S² → S²)-D -valine] ( 6 ) was synthesized by coupling N-(tert-butoxycarbonyl)-S-carboxymethyl-L -cysteine benzyl ester ( 1 ) with S-trityl-L -cysteinyl-D -valine benzyl ester and subsequent removal of the protecting groups. After reduction of the disulfide, the free tripeptide Cys (CH₂CO-Cys-D -Val) ( Ib ) was used as a substrate of isopenicillin-N synthetase in a cell-free conversion to 6-[2-((D -2-amino-2-carboxyethyl)thio)acetamido]penicillanic acid ( IIa ).     

Synthesis and Properties of sym-Triazine Derivatives. 18. Synthesis of N-Substituted 2,4-Diamino-6-(benzothiazolyl-2-thiomethyl)-sym-triazines

The condensation of methyl benzothiazolyl-2-thioacetate with N-substituted biguanides in the presence of sodium methylate gave 2-amino-4-(RR'-amino)-6-(benzothiazolyl-2-thiomethyl)-sym-triazines. In a number of cases the 1,1-disubstituted 5-(benzothiazolyl-2-thioacetyl)biguanides could also be separated and these could be cyclized by refluxing in DMF to the corresponding substituted sym-triazines described. The latter type of compound was also synthesized by treating 2-amino-4-trichloromethyl-6-(benzothiazolyl-2-thiomethyl)-sym-triazine with primary and secondary aliphatic and heterocyclic amines or by the reaction of N-substituted 2,4-diamino-6-chloromethyl-sym-triazines with 2-mercaptobenzothiazole.     

Stereoselective Formation of Ternary Copper(II) Complexes of (S)-Amino-acid Amides and (R)- or (S)-Histidine and (R)- or (S)-Tyrosine in Aqueous Solution

Formation constants of ternary complexes of Cu^II with (S)-amino-acid amides ((S)-phenylalaninamide, (S)-prolinamide, and (S)-tryptophanamide) and (R)- or (S)-histidine and (R)- or (S)-tyrosine were determined potentiometrically in aqueous solution. Significant stereoselectivity was presented by all three amides towards histidine, the diastereoisomeric complexes with ‘heterochiral’ ligands being more stable than those with ‘homochiral’ ligands (see Table 3). The stereoselectivity observed with (S)-phenylalaninamide and (S)-tryptophanamide may be explained on the basis of hydrophobic stacking interactions between 1H-imidazole and the aromatic side chain, favoured by the terdentate behaviour of histidine (see Fig.2), whereas repulsive effects seem to be prevalent with (S)-prolinamide. Only (S)-prolinamide and (S)-phenylalaninamide show appreciable stereoselectivity with tyrosine, which is bidentate, probably on account of repulsive interactions. The present results on the stability of ternary complexes in solution allow to draw some conclusions on the mechanism of chiral discrimination performed by Cu^II complexes of (S)-amino-acid amides added to the mobile phase in HPLC (reversed phase).     

Novel Trinor-eremophilanes (Dendryphiellin B,C, and D), Eremophilanes (Dendryphiellin E,F, and G), and Branched C9-Carboxylic Acids (Dendryphiellic Acid A and B) from the Marine Deuteromycete Dendryphiella salina (SUTHERLAND) PUGHet NICOT

Further investigation of global extracts from cultures of the marine deuteromycete Dendryphiella salina leads to the isolation of three novel trinor-eremophilanes esterified by branched C₉-carboxylic acids, dendryphiellin B (= (+)-(1R*,2S*,7R*,8aR*)-1,2,6,7,8,8a-hexahydro-7-hydroxy-1,8a-dimethyl-6-oxonaphthalen-2-yl (6R*, 2E, 4E)-6-hydroxy-6-methylocta-2,4-dienoate; (+)- 2 ), dendryphiellin C (=(+)-(1R*, 2S*, 7R*, 8aR*)-1,2,6,7,8,8a-hexa-hydro-7-hydroxy-1,8a-dimethyl-6-oxonaphthalen-2-yl (6S, 2E, 4E)-6-methylocta-2,4-dienoate; (+)- 3 )), and dendryphiellin D (=(+)-(1R*, 2S*, 7R*, 8aR*)-1,2,6,7(8,8a-hexahydro-7-hydroxy-1,8a-dimethyl-6-oxonaphthalen-2-yl (6R*,2E,4E)-6-(hydroxymethyl)octa-2,4-dienoate; (+)- 4 ). An intact eremophilane, dendryphiellin E ( 5 ), and its ethanolysis product dendryphiellin F whose absolute configuration is represented by structural formula (+)- 6 are also isolated from the above extracts. Dendryphiellin E exists as an open form 5a in equilibrium with a closed form 5b . A similar equilibrium exists between the open form 8a and the closed form 8b of a non-esterified eremophilane, dendryphiellin G ( 8 ), which is isolated too from the above extracts and proves structurally related to the cyclic portion of 5 . Finally, the free, branched C₉-carboxylic acids dendryphiellic acid A ((+)- 9 ) and B ((+)- 10 ) which correspond to side chains of the above esterified terpenes are also isolated from the above extracts.     

Markierte Vertreter eines möglichen Zwischenprodukts der Biosynthese von Fosfomycin inStreptomyces fradiae: Darstellung von (R,S)-(2-Hydroxypropyl)-, (R,S)-, (R)-, (S)-(2-Hydroxy-[1,1-2H2]propyl)-und (R,S)-(2-[18O]Hydroxypropyl)phosphonsäure

Summary Racemic methyl O-benzyllactate was reduced to the alcohol, transformed into the bromide and reacted with triethylphosphite to give the diethylphosphonate. Removal of protecting groups afforded a phosphonic acid which was purified as its cyclohexylammonium salt. (S)-Ethyl and (R)-isobutyl O-benzyllactate were reduced with LiAlD₄ to the corresponding dideuteriated alcohols, which were transformed in the same way as the racemic compound into the chiral (2-hydroxy-[1,1-²H₂]propyl)phosphonic acids. The optical purity of alcohols (S)- and (R)-6 b was determined by derivatisation with (+)-MTPA-Cl and¹H-NMR-spectroscopy to be 98%. Exchange of the carbonyl-16-oxygen atom of 2-oxopropylphosphonate for oxygen-18 from H₂ ¹⁸O, reduction with NaBH₄, deprotection and addition of cyclohexylamine yielded the salt (±)-18 of (2-[¹⁸O]hydroxypropyl)phosphonic acid.

     

Complexation behaviour of radiation synthesized poly(vinylbenzyltrimethylammonium chloride) and its gel with potassium hexacyanoferrates (II, III) and potassium persulfate in aqueous medium

High energy gamma radiation has been used to synthesize linear poly(vinylbenzyltrimethylammonium chloride) (PVBT) as well as crosslinked PVBT gels. Complexation behaviour of linear and crosslinked PVBT with K₂S₂O₈, K₃[Fe(CN)₆] and K₄[Fe(CN)₆] have been studied by viscometry, turbidity and equilibrium swelling measurements. The stoichiometry of the complex formed was found to be a function of charge on the anions of complexing species. Crosslinked poly(vinylbenzyltrimethylammonium chloride) gels were found to desorb some of the embedded water when swollen gels were placed in these salt solutions. Existence of strong ionic interactions between polymer chains and complexing salts was confirmed by changes in equilibrium swelling of complexed crosslinked matrices as well as in the stoichiometry of linear PVBT complexes in presence of strong electrolytes like NaCl.     

Complexes of nickel(II) withS-carboxyalkyl-L-cysteines in aqueous medium. Determination of enthalpies by thermometric titrimetry

Summary Molar heats for the reaction of nickel(II) with sulphur-containing amino acids,S-carboxymethyl-L-cysteine andS-carboxyethyl-L-cysteine, have been determined by thermometric titrimetry. The data refer to aqueous solutions at 25°C andI=2.0m. From these enthalpies and equilibrium constants, the corresponding entropies have been calculated. The present thermodynamic data are complementary to previous spectrophotometric data in explaining the structures of the complexes. In particular, the importance of solute-solvent external factors in determining different stabilities for successive steps of complex-formation is stressed.     

Potential propelling and rotating functions of propeller-type complexes. III. Detection of the propelling motion in fac-tris(S-2,3-diaminopropionato)cobalt(III) in an aqueous solution upon IR irradiation

Circular dichroism spectra of the fac and mer isomers of tris-cobalt(III) complexes of S-2,3-Hdap (Hdap?=?diaminopropionic acid); fac and mer-[Co(S-dap)₃] (Λ or Δ), and [Co(en)₃]³⁺ (Λ or Δ, en?=?ethylenediamine) in an aqueous solution without and upon IR irradiation were measured. The detection of the propelling motion that corresponds to circular dichroism spectral changes of the propeller-type complex, fac-[Co(S-dap)₃] in an aqueous solution upon IR irradiation gave good agreement with the computer-simulation result, that is, the propelling (translation and rotation) motion occurs in propeller-type metal complexes in aqueous solution as a consequence of an appropriate energy supply, which had been obtained by theoretical study based on molecular dynamics (MD) simulations by the use of AMBER 6 program.