An Improved Stereocontrolled Route to <Emphasis Type="Italic">cis</Emphasis>-Erythrinanes by Combined Intramolecular <Emphasis Type="Italic">Strecker</Emphasis> and <Emphasis Type="Italic">Bruylants</Emphasis> Reaction

Summary. Condensation of (2-iodophenyl)ethylamines with cyclohexanoylacetaldehyde provided the corresponding aldimines which were reduced yielding secondary phenethylcyclohexanoylethylamines. These in turn were appropriate intermediates to prepare several erythrinanes by a sequential intramolecular Strecker and intramolecular Bruylants reaction. In contrast, the C-ring homologue schelhammeranes were not available on this route.Part of PhD thesis, LMU München, D     

<Emphasis Type="Italic">Z</Emphasis>-and <Emphasis Type="Italic">E</Emphasis>-conformers of <Emphasis Type="Italic">N</Emphasis>-chloroacetylcytisine

N-Chloroacetylcytisine was synthesized by acylation of (–)-cytisine. Stable Z- and E-conformers with respect to rotational isomerism around the N-12–CO bond were found in PMR spectra at room temperature. The point at which PMR resonances of the Z- and E-conformers coalesced upon heating was measured. The transition barrier between the conformers was estimated.     

Molecular properties of the copolymers of <Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>-diallyl-<Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>-dimethylammonium chloride and maleic acid

The hydrodynamic and conformational properties of molecules of poly(N,N-diallyl-N,N-dimethylammonium chloride) and N,N-diallyl-N,N-dimethylammonium chloride-maleic acid copolymers of different compositions in solutions with various ionic-strength and pH values, as well as of the polyelectrolyte complex based on the copolymer with dodecyl sulfate anions in chloroform, are studied. For poly(N,N-diallyl-N,N-dimethylammonium chloride) molecules in a 1 M NaCl solution, the Kuhn segment length and the hydrodynamic diameter of the chain are estimated as A = 3.9 nm and d = 0.48 nm, respectively. In acidic solutions with pH 3.5, the copolymers demonstrate behavior typical for polyelectrolytes. In an alkaline solution with pH 13, when 1 M NaCl is added to the solution of the copolymer containing 29 mol % maleic acid units, there is an antipolyelectrolyte effect that manifests itself as an increase in the intrinsic viscosity of the copolymer and in the hydrodynamic radius of its molecules. It is found that an increase in the fraction of maleic acid units in the copolymer from 12 to 42 mol % brings about a reduction in the equilibrium rigidity of its macromolecules from 4.1 to 2.2 nm. The equilibrium rigidity of polyelectrolyte-complex molecules is higher than that of initial copolymer molecules owing to steric interactions arising between the aliphatic chains of dodecyl sulfate anions. In an electric field, the molecules of the complex are oriented owing to the induced dipole moment resulting from the displacement of dodecyl sulfate anions along the chain contour.     

Conformations and properties of <Emphasis Type="Italic">O</Emphasis>-Alkyl-<Emphasis Type="Italic">S</Emphasis>-(2-<Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>-dialkylamino)-ethylmethylthiophosphonates

Conformers of the biologically active compounds CH₃P(O)(OR)(SCH₂CH₂NR ₂ ^′ ), where (I) R = i-C₄H₉, R′ = C₂H₅ and (II) R = C₂H₅, R′ = i-C₃H₇, are calculated within the AM1 level of theory. The elongated and twisted forms with maximum and minimum distances between a nitrogen atom and those of a phosphorus tetrahedron, respectively, and bearing a syn and anti oriented alkoxy group relative to a phosphoryl oxygen, are studied. It is found that the differences between the energy, electronic, and geometric parameters of these forms are apparent in differences between their properties, e.g., the ability to participate in complexation and protonation, reactions that to some extent simulate the interaction between a substance and a biological object.     

Stability of <Emphasis Type="Italic">s</Emphasis>-, <Emphasis Type="Italic">p</Emphasis>-, and <Emphasis Type="Italic">d</Emphasis>-element diphosphates in water

The mean atomic Gibbs energies of formation of (Δ _f ? _at ⁰ ) of s-, p-, and d-element diphosphates have been calculated using ion increments of the Gibbs energy (Δ _f G ⁰). The diphosphate hydrolysis kinetics is considered, and a correlation between the Δ _f ? _at ⁰ values and the hydrolysis rate constants is presented.     

Mechanistic aspects of ligand substitution on <Emphasis Type="Italic">cis</Emphasis>-diaqua(<Emphasis Type="Italic">cis</Emphasis>-1,2-diaminocyclohexane)platinum(II) by Glycine-<Emphasis Type="SmallCaps">l</Emphasis>-Leucine

The kinetics of the interaction of glycine-l-leucine (Glyleu) with cis-[Pt(cis-dach)(OH₂)₂]²⁺ (dach = 1,2-diaminocyclohexane) has been studied spectrophotometrically as a function of [cis-[Pt(cis-dach)(OH₂)₂]²⁺], [Glyleu] and temperature at pH 4.0, where the complex exists predominantly as the diaqua species and Glyleu as a zwitterion. The substitution reaction shows two consecutive steps: the first is the ligand-assisted anation and the second is the chelation step. The activation parameters for both the steps were evaluated using Eyring’s equation. The low ∆H₁^≠ (51.9 ± 2.8 kJmol⁻¹) and large negative value of ∆S₁^≠ (−152 ± 8 JK⁻¹mol⁻¹) as well as ∆H₂^≠ (54.4 ± 1.7 kJmol⁻¹) and ∆S₂^≠ (−162 ± 5 JK⁻¹mol⁻¹) indicate an associative mode of activation for both the aqua ligand substitution processes.     

Analysis of <Emphasis Type="Italic">Escherichia coli</Emphasis> nicotinate mononucleotide adenylyltransferase mutants <Emphasis Type="Italic">in vivo</Emphasis> and <Emphasis Type="Italic">in vitro</Emphasis>

Background  

Adenylation of nicotinate mononucleotide to nicotinate adenine dinucleotide is the penultimate step in NAD⁺ synthesis. In Escherichia coli, the enzyme nicotinate mononucleotide adenylyltransferase is encoded by the nadD gene. We have earlier made an initial characterization in vivo of two mutant enzymes, NadD72 and NadD74. Strains with either mutation have decreased intracellular levels of NAD⁺, especially for one of the alleles, nadD72.     

Copolymer of <Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>-diallyl-<Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>-dimethylammonium chloride with maleic acid as drug carrier

A copolymer of N,N-diallyl-N,N-dimethylammonium chloride with maleic acid of constant composition was prepared under the conditions of radical initiation. The possibility of the functionalization of the copolymer with drugs containing amino groups by polymer-analogous transformations was examined. Conditions were found for preparing conjugates of the copolymer with isoniazid. The structures and the quantitative compositions of the conjugates were determined by ¹³С NMR spectroscopy, and the possibility of preparing conjugates with controlled drug content was demonstrated.     

Asymmetric synthesis and stereochemistry of chiral <Emphasis Type="Italic">cis</Emphasis>- and <Emphasis Type="Italic">trans</Emphasis>-3-alkyl-4-aminopiperidines

Chiral nonracemic 3-substituted cis- and trans-4-aminopiperidines, which are precursors of anilidopiperidine analgesics, were obtained by diastereoselective synthesis from 1-methyl- and 1-benzyl-4-[(S)-1-phenylethyl]iminopiperidines, using the following reaction sequence: metalation with lithium diethylamide, alkylation with alkyl halides, and hydride reduction or hydrogenation over Raney nickel. The steric direction of the reaction, three-dimensional structure, preferred conformation, and absolute configuration of the resultant aminopiperidines were determined.     

Thermolysis of dimethyl <Emphasis Type="Italic">cis</Emphasis>- and <Emphasis Type="Italic">trans</Emphasis>-1 pthalimidoaziridine-2,3-dicarboxylates in the presence of dipolarophiles

Thermolysis of dimethyl esters of stereoisomeric phthalimidoaziridine-2,3-dicarboxylic acids in the presence of dimethyl fumarate, dimethyl maleate, and N-phenylmaleimide occurred stereo-specifically and stereoselectively led to the formation of derivatives of 1-phthalimidopyrrolidine, products of 1,3-dipolar additrion of intermediately arising azomethine ylides. In keeping with the rules of the conservation of orbital symmetry the thermal opening of the 2,3-disubstituted 1-phthalimidoaziridines into azomethine ylides occurred conrotatory. The relative positions of the substituents in the dipolarophiles is retained in the reaction products indicating the concerted addition mechanism.     

Synthesis of 6-methyl-8<Emphasis Type="Italic">H</Emphasis>-dibenzo[<Emphasis Type="Italic">a</Emphasis>,<Emphasis Type="Italic">g</Emphasis>]quinolizin-8-imines <Emphasis Type="Italic">via Reissert</Emphasis> compounds

Alkylation of Reissert compounds derived from 3-methylisoquinolines with several 2-cyanobenzylbromides followed by hydrolytic cleavage provided the corresponding 1-benzyl-3-methylisoquinolines. Treatment of the latter with methylmagnesiumiodide caused cyclization to the title compounds rather than formation of 2-acetylbenzylisoquinolines.     

Lipids from <Emphasis Type="Italic">Halostachys caspica</Emphasis> and <Emphasis Type="Italic">Halocharis hispida</Emphasis>

The composition of lipids from the aerial parts of two species of halophytes from the family Chenopodiaceae, Halostachys caspica C. A. Mey. and Halocharis hispida Bge. was determined. Neutral lipids (NL, 62.1 and 54.2%, respectively) dominated the total lipids (TL) of these plants. More than a third of the NL were esters of aliphatic alcohols and phytosterols (FAE). Fatty acids 16:0, 18:1, and 18:2 dominated the acids of FAE; 16:0, 18:1, and 18:3, the phospholipids. The principal fatty acids of glycolipids were unsaturated acids (68.3 and 75.1%) with linolenic acid dominating (44.9 and 43.5%). Presented at the 7th International Symposium on the Chemistry of Natural Compounds, Tashkent, October 16–18, 2007. Translated from Khimiya Prirodnykh Soedinenii, No. 3, pp. 276–278, May–June, 2009.     

Molecular structure of <Emphasis Type="Italic">N</Emphasis>-(<Emphasis Type="Italic">o</Emphasis>-and <Emphasis Type="Italic">p</Emphasis>-hydroxybenzyl)cytisine

The molecular structures of N-(o-and p-hydroxybenzyl)cytisine were investigated by NMR spectroscopy, x-ray structure analysis, and molecular modeling. It was found that NMR resonances of the OH and aromatic protons in N-(o-hydroxybenzyl)cytisine were doubled because of the presence of two conformers in solution. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 165–168, March–April, 2008.     

Synthesis of <Emphasis Type="Italic">N</Emphasis>-and <Emphasis Type="Italic">C</Emphasis>-trimethylsilyl-substituded anililes

N-Metallation of bromoanilines with ethylmagnesium bromide followed by a reaction with trimethylchlorosilane provided N-mono and N-bis(trimethylsilyl)bromoanilines depending on the structure of substrate. The metallation of bissilylated bromoanilines with butyllithium permitted the introduction of a trimethylsilyl substituent in the aromatic ring. Previously unknown 2-bromo-N,N-bis(trimethylsilyl)aniline, 2,6-dibromo-N-trimethylsilylaniline, 2,6-dibromo-N,N-bis(trimethylsilyl)aniline, 2-bromo-6-trimethylsilylaniline, 2-bromo-6-trimethylsilyl-N,N-bis(trimethylsilyl)aniline, 2-bromo-6-trimethylsilyl-N-trimethylsilylaniline, 2,4,6-tribromo-N-trimethylsilylaniline, and 2,4,6-tribromo-N,N-bis(trimethylsilyl)aniline were prepared. The structures of the compounds obtained were established by the chromato-mass spectrometry and ¹H, ¹³C, and ²⁹Si NMR spectroscopy.     

Synthesis of <Emphasis Type="Italic">N,N</Emphasis>-disubstituted (<Emphasis Type="Italic">Z</Emphasis>)-<Emphasis Type="Italic">O</Emphasis>-methylnicotinamide oximes

A number of (Z)-N,N-dialkyl- and (Z)-N-acyl-N-alkyl-O-methylnicotinamide oximes was synthesized. Their configuration was confirmed by the NOESY experiment. Evaluation of fungicidal activity of compounds obtained was performed.     

Photolysis of <Emphasis Type="Italic">ortho</Emphasis>-azidophenol in various solvents

The photolysis of ortho-azidophenol in water, ethanol, acetonitrile, chloroform, and benzene was studied by IR and electronic spectroscopy and thin-layer chromatography. It was found that an equilibrium between ortho-azidophenol and its quinonoid form occurred in benzene. In the photolysis of ortho-azidophenol in benzene, intramolecular hydrogen bonding facilitates the degradation of the azido group through the mechanism of formation of intermediate triazene structures. In the other solvents, which exclude intramolecular hydrogen bonding, the nitrene mechanism of photolysis yielding ortho-aminophenol, ortho-iminoquinone, and an azo compound is operative. The rate of formation of photolysis products depends on the nature of the solvent.     

Synthesis of <Emphasis Type="Italic">o</Emphasis>(<Emphasis Type="Italic">m</Emphasis>)-carborane-containing azomethines

A method of preparative synthesis of o(m)-carborane-containing azomethines via the condensation of o(m)-carboranyl-C-methylene-4-formylbenzoates with aliphatic, cycloaliphatic, and aromatic amines was developed.     

Isolation and characterization of the cellulose synthase genes <Emphasis Type="Italic">PpCesA6</Emphasis> and <Emphasis Type="Italic">PpCesA7</Emphasis> in <Emphasis Type="Italic">Physcomitrella patens</Emphasis>

Analysis of cellulose biosynthesis using molecular approaches has been successful in identifying genes in many cellulose-producing organisms, yet the mechanism of cellulose biosynthesis still remains to be understood. We are interested in developing the moss Physcomitrella patens as a useful system for the study of cellulose biosynthesis. This moss affords a number of advantages including a haploid dominated gametophyte and a very high efficiency of homologous recombination in its nuclear DNA for constructing gene knockouts. In addition, P. patens has only a primary cell wall unlike Arabidopsis thaliana, which has both a primary and a secondary cell wall. We identified two full-length cellulose synthase (CesA) genes of P. patens, PpCesA6 and PpCesA7 from an EST database and have analyzed the genomic sequences. PpCesA6 and PpCesA7 show high similarity to each other, both at the cDNA and genomic DNA levels. Single and double knockouts of PpCesA6 and PpCesA7 were generated and screened for phenotypic changes. While the PpCesA6 and PpCesA7 single knockouts did not show any obvious phenotypic differences from the wild-type, the double knockout had significantly reduced stem length. These results suggest that PpCesA6 and PpCesA7 probably have a very similar role in cellulose biosynthesis and their functions may be redundant. Additionally, their roles may overlap with the other P. patens CesAs as observed for CesAs involved in primary cell wall biosynthesis in A. thaliana.