Substituted 1,2-Thiazetidine 1,1-Dioxides. Synthesis of (<Emphasis Type="Italic">RS</Emphasis>)- and (<Emphasis Type="Italic">S</Emphasis>)-1,2-Thiazetidine-3-acetic Acid 1,1-Dioxide and its Reactions with Amino Acids and Dipeptides

Summary. (RS)-2-tert-Butyldimethylsilyl-1,2-thiazetidine-3-acetic acid 1,1-dioxide prepared from (RS)-S-benzyl--homocysteine was condensed via DCC/NHS with various L-amino acid esters or dipeptide esters yielding N-silylated -sultam peptides. A -sultam active ester was isolated as an intermediate. Desilylation with TBAF in THF yielded stable N-unsubstituted products, and deprotection of the benzyl esters was achieved by catalytic hydrogenation. (S)-S-Benzyl--homocysteine was obtained by fractional crystallization of the brucine salt of the racemate and transformed into benzyl (S)-1,2-thiazetidine-3-acetate, which was on the other hand synthesized by an enantiospecific route from -benzyl Boc-L-aspartate. Some -sultam peptides were prepared from the (S)-enantiomer, and finally some -sultam peptides containing D-Ala units were obtained.     

Synthesis of Spiro and Fused Five Membered <Emphasis Type="Italic">N</Emphasis>-Heterocycles from Alkylidenephosphoranes

Summary. Triketoindan-2-oxime reacted readily with ethoxycarbonylmethylene triphenylphosphorane to give mainly the corresponding spiro-pyrrole (38%) along with the fused 1-hydroxydihydropyrrole (14%), whereas the spiro-dimer (29%) was obtained from the reaction of the oxime with methoxycarbonylmethylenetriphenyl phosphorane in addition to the corresponding 1-hydroxydihydropyrrole (31%). Conversely, Wittig products, mono-olefin (52%) and diolefin (<7%) along with the reduced substrate (10%), were observed when the oxime was treated with a cyano ylide. The reactions of the oxime with allyl- and vinyl phosphonium salts proceeded under phase-transfer catalysis to afford fused oxazole (46%) and spiro[2]oxazole (17%), while with the latter the fused 1-hydroxypyrrole (55%) was produced.Received February 26, 2003; accepted (revised) March 19, 2003 Published online August 28, 2003     

Phytoecdysteroids from <Emphasis Type="Italic">Serratula komarovii</Emphasis>

Integristerone A and 2-deoxy-20-hydroxyecdysone were observed for the first time in the aerial and subterrean organs of the eastern Asian plant Serratula komarovii Iljin. -Ecdysone was not found in the plants. The dynamics of phytoecdysteroid content (integristerone A, 20-hydroxyecdysone, and 2-deoxy-20- hydroxyecdysone) in the vegetative and generative organs of this species were investigated.Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 404–406, September–October, 2004.     

The costly process of creating a cavity in <Emphasis Type="Italic">n</Emphasis>-octanol

Free-energy perturbation calculations are used to evaluate the free energy of cavity formation in n-octanol. A detailed theoretical analysis of the procedure is given and some limiting value phenomena are discussed. The data become subject to a three-parameter fit and a revised formulation of the popular approach due to Pierotti of calculating cavitation free energies is given. Pierottis approach is based on the equation derived from scaled particle theory (SPT) by Reiss et al. [(2000) J. Chem. Phys. 31:369–380]. The revision of Pierottis approach has the important advantage of being completely independent of the solvent hard-sphere radius, an empirical parameter in the standard procedure, which is hard to define in a uniformly valid way.Acknowledgments. S.H. gratefully acknowledges supercomputing support from the University of Linz, GUP, Professor Volkert and Dr. Kranzlmüller, and the University of Salzburg, RIST⁺⁺, Professor Zinterhof.Proceedings of the 11th International Congress of Quantum Chemistry satellite meeting in honor of Jean-Louis Rivail     

Amperometric determination of live <Emphasis Type="Italic">Escherichia coli</Emphasis> using antibody-coated paramagnetic beads

Detecting and enumerating fecal coliforms, especially Escherichia coli, as indicators of fecal contamination, are essential for the quality control of supplied and recreational waters. We have developed a sensitive, inexpensive, and small-volume amperometric detection method for E. coli -galactosidase by bead-based immunoassay. The technique uses biotin-labeled capture antibodies (Ab) immobilized on paramagnetic microbeads that have been functionalized with streptavidin (bead–Ab). The bead–Ab conjugate captures E. coli from solution. The captured E. coli is incubated in Luria Bertani (LB) broth medium with the added inducer isopropyl -D-thiogalactopyranoside (IPTG). The induced -galactosidase converts p-aminophenyl -D-galactopyranoside (PAPG) into p-aminophenol (PAP), which is measured by amperometry using a gold rotating disc electrode. A good linear correlation (R²=0.989) was obtained between log cfu mL^–1 E. coli and the time necessary to product a specific concentration of PAP. Amperometric detection enabled determination of 2×10⁶ cfu mL^–1 E. coli within a 30 min incubation period, and the total analysis time was less than 1 h. It was also possible to determine as few as 20 cfu mL^–1 E. coli under optimized conditions within 6–7 h. This process may be easily adapted as an automated portable bioanalytical device for the rapid detection of live E. coli.     

Orthogonally Protected,Carboxy-Activated <Emphasis Type="Italic">L</Emphasis>-Homoisoserine, 2-Methyl-<Emphasis Type="Italic">L</Emphasis>-homoisoserine,and Homoisocysteine Derivatives. New Building Blocks for Peptide and Depsipeptide Modification

Summary. Starting from L-malic, L-citramalic, and rac. thiomalic acids routes to L-homoisoserine, 2-methyl-L-homoisoserine and rac. homoisocysteine have been developed. The new orthogonally protected and carboxy-activated building blocks are GABA as well as -hydroxy and -mercapto acid derivatives, suitable for the construction of peptide and depsipeptide surrogates.     

A Novel Stereoselective Synthesis of <Emphasis Type="Italic">cis</Emphasis>-Configured Erythrinane and Erythrinane Type Analogues

Summary. N-Alkylation of certain angularly substituted heterocycles by C₂- and C₃-units provided appropriate precursors to construct stereoselectively the erythrinanone and several erythrinanone type analogues by intramolecular Friedel-Crafts acylation. The resulting aromatic ketones were catalytically reduced affording the corresponding parent frameworks including the hitherto unknown tetracyclus A-norschelhammerane. On the other hand, the stereoselective reduction of the carbonyl moiety offered a convenient approach to 11-hydroxylated erythrinanes with the natural occurring -configuration. The structures and the stereochemistry of the target compounds were proved by NMR spectroscopy.Part of PhD thesis, LMU München, D     

A Biokinetic Model to Describe Consequences of Inhibition/Stimulation in <Emphasis Type="Italic">DNA</Emphasis>-Proofreading and -Repair,Part 4

Summary. In previous papers a strongly simplified physical-mathematical (biokinetic) model has been presented, which dealt with the factors influencing the timely development of DNA mismatches dependent cells (malignant cells) in their kinetic competition to the development of normal somatic cells (i.e. cells with correct genetic information). The kinetic results have been studied by comparing them with experimental results reported in the literature upon inhibiting the organisms own enzymatic DNA-proofreading and repair machinery. In spite of the fact that the model uses fully the chances of kinetics, which allows to describe even rather complicated systems with many regulation circuits and feed back loops in a rather simple, summarizing way, it has been demonstrated that the model does not only well describe the experimentally found significant increases of mutants in cases when the DNA repair system has been inhibited, but it can also reflect cancer-development and the efficacy of classical cancer therapies like surgery or chemotherapy as well.In applying the predictions of the model as to the opposite of an inhibition of the DNA repair system, i.e., in testing the results, if the organisms own repair systems were stimulated, the model shows that there could be a chance for a new, adjuvant cancer-therapy if this concept was combined with biochemical facts and clinical findings which are reported in the literature.In continuation of this concept, the predictions of the model have been compared with findings upon cancer-therapies by apoptosis-triggerers like tamoxifen. Further, according to the fact that there exists literature by which it is demonstrated by clinical facts that it is not necessary to use living cells (e.g. from umbilical cords blood or bone-marrow) to achieve surprising therapeutic successes in cancer therapy, but also cell-free human-placenta-extracts (HPEs) can be similarily effective, it has been tried in a first preliminary analytical effort to characterize effector-substances contained therein.Received January 27, 2003; accepted (revised) March 25, 2003 Published online August 18, 2003     

2-Methylthio-4,5,6,7-tetrahydro-1,2,4-triazolo[1,5-<Emphasis Type="Italic">a</Emphasis>]pyrimidin-5- and -7-Ones

The cyclocondensation of methylcinnamates and arylidene derivatives of Meldrums acid with 3-amino-5-methylthio-1,2,4-triazole in DMF gives 2-methylthio-4,5,6,7-tetrahydro-1,2,4-triazolo[1,5-a]-pyrimidin-5-ones. The reaction involving arylidene derivatives of Meldrums acid or its synthetic equivalents in ethyl acetate with a catalytic amount of pyridine gives a mixture of 2-methylthio-4,5,6,7-tetrahydro-1,2,4-triazolo[1,5-a]pyrimidin-5- and -7-ones.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 246–251, February, 2005.     

Synthesis of Side Chain Substituted 3-Butylisocoumarins and Absolute Configurations of Natural Isocoumarins from <Emphasis Type="Italic">Artemisia dracunculus</Emphasis>

Summary. A series of 3-hydroxy- and 3-bromobutyl-substituted isocoumarins was synthesized. The absolute configurations of three isocoumarin derivatives from Artemisia dracunculus, namely (–)-epoxyartemidin, (–)-2-methoxydihydroartemidin, and (+)-3-hydroxyartemidin were determined by chemical means via derivatization, kinetic racemate resolution (Horeau method), and comparison of the circular dichroism (CD) spectra.DeceasedReceived March 17, 2003; accepted March 19, 2003 Published online August 18, 2003     

Synthesis of 1,2,3,9a-tetrahydro-9H-imidazo[1,2-<Emphasis Type="Italic">a</Emphasis>]indole-2-thione and 1,5,6,10b-Tetrahydroimidazo[2,1-<Emphasis Type="Italic">a</Emphasis>]-isoquinoline-2(3H)-thione derivatives

Thionation of 1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indol-2-one derivative with Lawessons reagent in boiling toluene afforded 1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indole-2-thione derivative. Alkylation of the latter with ethyl iodide in DMF in the presence of a strong base gave 2-ethylthio-9,9,9a-trimethyl-9,9a-dihydro-3H-imidazo[1,2-a]indole. 1,5,6,10b-Tetrahydroimidazo[2,1-a]isoquinoline-2(3H)-thiones were synthesized by thionation of the corresponding carbonyl substrates.Published in Khimiya Geterotsiklicheskikh Soedinenii, No 11, pp. 1695–1700, November, 2004.     

Synthesis of a Calix[4]arene Containing 'Hard' and 'Soft' Metal Ion Binding Sites

Co-receptor 1,3-calix[4]-di(aza-benzo)crown-crown-6 (1-H) designed with one calix[4]arene in a 1,3-alternate conformation and hard and soft metal ion binding sites has been prepared according to three pathways (A-C). Pathway B, consisting of two different 1 + 1 condensations with ditosylate derivatives, was shown to be the most efficient.     

Modification of the<Emphasis Type="Italic"> Limulus</Emphasis> amebocyte lysate assay for the analysis of glucan in indoor environments

-1,3-d-Glucan is a biologically active component mainly from fungi that has been shown in several studies to be related to respiratory health outcomes from damp building exposures. Here, we report the development and application of a method for the analysis of the glucan extracted in 0.5 N NaOH solution making use of an available preparation of Limulus amebocyte lysate (LAL). The method yields reproducible -1,3-d-glucan measurements from samples of outdoor air, yeast cells, fungal spore preparations and ragweed pollen, and is more sensitive than competing measurements. The LAL-based measurement compared favourably to that based on size-exclusion chromatography using UV and refractive index detection. Growth conditions of the fungi did not materially change the concentrations of glucan in spores indicating that this is a stable property. Glucan content was proportional to spore surface area; however, some species contain higher relative spore glucan contents.     

Reaction Between Alkyl Isocyanides and Cyclic 1,3-Diketones: A Convenient Synthesis of Functionalized 4<Emphasis Type="Italic">H</Emphasis>-Pyrans

Summary. Alkyl isocyanides react with dialkyl acetylendicarboxylates in the presence of CH-acids such as cyclopentane-1,3-dione, cyclohexane-1,3-dione, or 5,5-dimethylcyclohexane-1,3-dione to afford highly functionalized 4H-pyrans in fairly high yields. In the case of reaction between dimethyl acetylenedicarboxylate and 5,5-dimethylcyclohexane-1,3-dione in the presence of cyclohexyl isocyanide or benzyl isocyanide tetrahydro-cyclopenta[b]pyran derivatives were isolated in addition to the 4H-pyran system. The free energy barrier (96.9kJmol^–1) for restricted rotation around the polarized double bond of the enaminone moiety in dimethyl 2-[cyclohexylamino-(4,4-dimethyl-2,6-dioxocyclohexylidene)methyl]but-2-enedioate was determined by dynamic NMR spectroscopy.     

A new hydroquinone diglucoside from <Emphasis Type="Italic">Lysimachia fordiana</Emphasis>

A new hydroquinone diglucoside along with five known compounds was isolated from the whole plant of Lysimachia fordiana Oliv. The structure of the new compound was determined to be 2-heptyl-6-methoxy-1,4-hydroquinone-1,4-di-O--D-glucopyranoside (6). The five known compounds were identified as pentacosane (1), stigmasterol (2), 2-heptyl-6-methoxy-1,4-benzoquinone (3), palmitic acid (4), and rutin (5), respectively. This is the first report of the isolation of Lysimachia fordiana Oliv. in the family Primulaceae.Published in Khimiya Prirodnykh Soedinenii, No. 5, pp. 377–379, September–October, 2004.     

Isolation and characterization of tautomeric forms of 2,4-diacetyl-3-(<Emphasis Type="Italic">o</Emphasis>-R-aryl)-5-hydroxy-5-methylcyclohexanones

Keto-enol prototropic tautomerism of 2,4-diacetyl-3-(o-R-aryl)-5-hydroxy-5-methylcyclohexanones in the -diketone fragment was studied. Individual tautomeric forms of -diketones, viz., keto and enol forms, were isolated and characterized. The latter are generated through enolization of the alicyclic carbonyl group. Enolization is facilitated by the presence of an ortho substituent in the benzene ring.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2670–2674, December, 2004.     

Die Acetalgruppe, 1. Mitt. Acetale von Halogenmethyl-arylcarbinolen

Several halomethyl-arylcarbinols were prepared, and the influence of substituents on enantiomer selectivity in the acetalisation reaction with [2S-(2,3a,4,7,7a)]-octahydro-7,8,8-trimethyl-4,7-methanobenzofuran-2-ol was examined.

Unserem sehr verehrten Lehrer, Herrn Prof. Dr.Otto Hromatka, mit den besten Wünschen zum 80. Geburtstag gewidmet.     

<Emphasis Type="Italic">Ab initio</Emphasis> structural study of M(mda)<Subscript>2</Subscript> complexes (M = Be,Mg, Ca; mda = C<Subscript>3</Subscript>O<Subscript>2</Subscript>H<Subscript>3</Subscript>)

The structure of M(mda)₂ (M = Be, Mg, Ca; mda = C₃O₂H₃) bis-complexes was investigated by the ab initio Hartree-Fock method and by including electron correlation in terms of second order Möller-Plesset perturbation theory; for calculations we used triple-zeta valence basis sets complemented with polarization functions. Two most probable geometrical nuclear configurations (D _2h and D _2d ) are considered for each molecule. The structure with two mutually orthogonal chelate ligands (D _2d symmetry) corresponds to the potential energy surface (PES) minimum. The planar D _2h configuration corresponds to the first order saddle point on PES; consequently, its relative energy determines the height of the barrier to the D _2d D _2h D _2d intramolecular rearrangement. Correlation equations that relate the calculated values of equilibrium internuclear distances, force constants, and rearrangement barrier heights to the value of the ionic radius of the metal atom have been obtained. These correlations were employed to evaluate the molecular constants for Sr(mda)₂ and Ba(mda)₂. The theoretical data are compared with the available experimental literature data.Original Russian Text Copyright © 2004 by V. V. Sliznev, S. B. Lapshina, and G. V. GirichevTranslated from Zhurnal Strukturnoi Khimii, Vol. 45, No. 4, pp. 611–623, July–August, 2004This revised version was published online in April 2005 with a corrected cover date.     

Spectroscopic detection of theendo-enol form of 2-acetylcyclopentane-1,3-dione

According to vibrational spectroscopic data, in the gas phase at 280 °C and in crystals prepared by sublimation, 2-acetylcyclopentane-1,3-dione was established to exist not as trione 1 but as the enol-form 2 with an exo-cyclic C=C bond (v(C=C) = 1593 cm^–1) and an intramolecular hydrogen bond. The enol 3 prepared by crystallization from CCl₄ is also stabilized by an intramolecular H-bond but has anendo-cyclic C=C bond (v(C=C) = 1545 cm^–1). In a trichloroethylene solution, both theexo- andendo-enol forms co-exist, and the percentage of the latter is 11 %. The frequencies in the vibrational spectra have been assigned using the normal coordinate calculation of2, 3, and their OD-analogs. The mechanism of tautomer transfer is discussed in terms of PMO theory.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 57–62, January, 1994.The authors are grateful to professor J. G. Ramos (Madrid Institute of Optics) for making it possible to record the far IR and Raman spectra in his laboratory, to Dr. V. Z. Kurbako for the registration of spectra and its discussion, and to Dr. N. A. Kubasova for recording the Raman spectra with a Coderg Ar-300 instrument.     

Three New <Emphasis Type="Italic">in situ</Emphasis> Syntheses of <Emphasis Type="Italic">N</Emphasis>-Acyl-α-triphenylphosphonioglycinates

Summary. N-Acyl--hydroxyglycinates were transformed into N-acyl--triphenylphosphonioglycinates by (i) phosphorylation with Ph ₃PBr₂ in the presence of Et ₃N or (ii) in reaction with DCC and Ph ₃P·HBF₄ in the presence of catalytic amounts of Ph ₃P as well as (iii) by a new kind of Mitsunobu reaction with Ph ₃P·HBF₄ as a nucleophile conjugated acid. The N-acyl--triphenylphosphonioglycinates can be effectively used without isolation for a nucleophilic displacement of the triphenylphosphonium group to obtain corresponding -substituted -amino acid derivatives.