Showing papers in "Helvetica Chimica Acta in 1974"

[Metabolites of microorganisms. 143. Echinocandin B, a novel polypeptide-antibiotic from Aspergillus nidulans var. echinulatus: isolation and structural components].

Abstract: From a strain of Aspergillus nidulans var. echinulatus, A 32204, echinocandin, a novel polypeptide antibiotic complex with high and specific anti-yeast activity was isolated. The main component, echinocandin B, was separated by counter-current distribution. A tentative molecular formula C52H81N7O18 is discussed. The antibiotic is characterized by its IR. and NMR. spectra and by its characteristic hydrolytic degradation products: linoilic acid, L-4-hydroxyproline, L-4-oxoproline, (2S, 3S, 4S)-4-methyl-3-hydroxy-proline, L-threonine (2 mols), and 1-(p-hydroxyphenyl)-3-amino-propan-2-one.

Isolierung und Strukturaufklärung von Chlamydocin

Abstract: The constitution of Chlamydocin – a metabolite of Diheterospora chlamydosporia with pronounced cytostatic activity – is proposed on the basis of chemical reactions and physical data. The synthesis of a derivative of a new amino acid is described. The biological activities of this compound and of derivatives of Chlamydocin are discussed.

An Investigation of the Tea Aroma. Part I. New volatile black tea constituents

Abstract: A total of 68 constitutents, mainly aldehydes, ketones and esters, have been identified for the first time in a black tea aroma concentrate using coupled gas-chromatography/mass spectrometry.

Limitations of Affinity Chromatography: Solvolytic Detachment of Ligands from Polymeric Supports

Abstract: Ligands of the RNH2 type which are covalently bound to agarose, cellulose, or cross-linked dextranes by the conventional cyanogen bromide method are slowly detached from their supports by solvolytic processes occurring above pH 5 in aqueous surroundings. At pH values between 5 and 10, the free ligands, RNH2, appear in solution. Above about pH 10, the carbamyl derivative of the ligand, RNHCONH2, is the main product. Dilute ammonia releases iminocarbamyl derivatives, RNHC(NH)NH2. The latter type of compound has also been observed in tris(hydroxymethyl)-aminomethane buffers at pH 8 and 9. Possible reaction mechanisms have been formulated on the basis of the structures suggested by Axen & Ernback for activated and substituted polysaccharides. Ligands attached to polyacrylamide gels (A) through amide bonds to carboxyl groups of the carrier, RNHCO·A, are released at slower rates and invariably as the free, unsubstituted ligand molecules. The release reaction appear to be general and independent of the particular ligand structure. We therefore advise caution with all experiments that can be adversely influenced by the presence of free ligands (e.g. localization of hormone receptors on the cell surface). At pH5, sepharose-bound 8-(ϵ-aminocaproyl-β-aminoethylthio)-adenosine-3′, 5′-cyclo-monophosphate removes cyclic 3′, 5′-adenosine-monophosphate-binding proteins from their solutions, but the corresponding polyacrylamide derivative does not (pH 7).

Bildung von Estern und Lactonen durch Silberionen‐Katalyse

Abstract: A mild and efficient method for the preparation of esters has been found in the silver ion induced reaction of alcohols with 2-pyridyl esters of thiocarboxylic S-acids. Examples are given to show the utility of this push button activation for the rapid formation of macrocyclic lactones and esters at room temperature under non-basic conditions.

Totalsynthese von Humaninsulin unter gezielter Bildung der Disulfidbindungen. Vorläufige Mitteilung

Abstract: A preliminary account is given of a total synthesis of human insulin involving directed formation of the three disulfide bonds at different stages of the fragment-condensation approach. The synthesis was facilitated by the application of two new methods for the selective removal of protecting groups. In the first, two S-Trt-protected cysteine residues are converted to the disulfide without affecting S-Acm-protected cysteine residues. The second new method consists in a very mild, pH-controlled, acidolysis of N(α)-Trt, leaving intact N(α)-Bpoc and other acid-labile protecting groups. The last step of the synthesis was the formation of the disulfide bridge between the Acm-protected cysteine residues A7 and B7 by iodine. Extensive counter-current distribution yielded the synthetic hormone in pure form. It was compared and found to be identical with natural human insulin. Identification was achieved by means of thinlayer chromatography and electrophoretic procedures, as well as by comparing the pattern of break-down by enzymes (finger-printing). The natural and synthetic hormones were crystallized under identical conditions. The synthetic human insulin was found to possess full biological activity in an in vitro system.

The Electronic Spectra of Unsubstituted Mono‐ to Pentaacetylene in the Gas Phase and in Solution in the Range 1100 to 4000 Å

Abstract: The electronic spectra of the title compounds I (n), n = 1 to 5, were recorded under standard conditions for quantitative comparison. Spectra of I(1) to I(4) in the gas phase and of I(2) to I(5) in nonpolar solutions are presented in a computer plotted form, and wave length maxima and intensities are listed. Tentative assignments of the medium-intensity, first transition (A band) and the ultrahigh-intensity, second transition (B band) are given. Finally, spectra of I(2) to I(5) recorded at − 150° are presented and discussed (A band). The syntheses of I(3) to I(5) are given in detail.

Vitamin D3 metabolites. I. Synthesis of 25-hydroxycholesterol.

Abstract: 25-Hydroxycholesterin (4) ist in 30proz. Ausbeute in sieben Schritten aus Stigmasterin (6) hergestellt worden. Der wichtigste Schritt ist die Umsetzung des Tosylats 11 mit dem Acetylenderivat 13 zu 14 unter Bildung des vollstandigen Cholesteringerusts.

Allenic and Acetylenic Spiropiperidine Alkaloids from the Neotropical Forg, Dendrobates histrionicus

Abstract: Four analogs of the acetylenic alkaloid, histrionicotoxin (C19H25NO) and the allenic alkaloid, isodihydrohistrionicotoxin have been isolated from extracts of skins of the arrow poison frog, Dendrobates histrionicus and characterized as neodihydrohistrionicotoxin, tetrahydrohistrionicotoxin, isotetrahydrohistrionicotoxin and octahydrohistrionicotoxin. These spiropiperidine (8-hydroxy-1-azaspiro[5.5]undecane) alkaloids differ only in the degree of unsaturation in the five carbon atoms (position 2) and four carbon atoms (position 7) side chains. A fifth compound, HTX-D, corresponds in empirical formula to a tetrahydrohistrionicotoxin with a 7-(cis-1-butenyl-3-ynyl) side chain, but the major mass spectral fragmentation with loss of C2H5O is not characteristic of the histrionicotoxins. Reduction of histrionicotoxin with hydrogen and Lindlar catalyst affords an isomeric dihydrohistrionicotoxin with the terminal acetylene of the five carbon atoms side chain reduced, tetrahydrohistrionicotoxin and hexahydrohistrionicotoxins, while reduction with hydrogen and palladium on charcoal affords dodecahydrohistrionicotoxin which is readily methylated to the tertiary amine by methyl iodide.

Selektive Synthesen mit Organometallen II: Metallierung und Abwandlung funktionell substituierter Alkene

Abstract: 1,4-Dienes, vinyl ethers, allyl ethers, allyl thio ethers, and propenethiolates were metalated by BuLi in the presence of an activator such as KOCMe3. Since the solvent, the counter-ion, or the temp. may be varied before subsequent treatment with an electrophile, the crit. ratio of direct vs. vinylogous attack (substitution at the a- or g-position, resp.) can be adjusted within large limits. Stereoselectivity was also achieved. [on SciFinder (R)]

Absolute Konfiguration von Xanthophyll (Lutein)

Abstract: Aufgrund von Abbauresultaten an naturlichem (+)-Xanthophyll (Lutein) und Xanthophyllathern und eingehender NMR.-Analyse (insbesondere am Abbau-Ionon V), Synthesen und chiroptischen Korrelationen wird bewiesen, dass (+)-Xanthophyll (3R:3′R:6′R)-Chiralitat hat. Fruher gemachte Vorschlage anderer Autoren sind zu korrigieren. Reduktion von Xanthophyll mit LiAlH4/AlCl3 gibt 3-(R)-Hydroxy-3′,4′-dehydro-6(ξ)-β,γ-carotin. Mit 1-Phenyl-5-chlortetrazol(Base) tritt Wasserabspaltung im β-Ring zu 3,4-Dehydro-6′-(R)-3′-(R)-hydroxy-β-carotin ein. Die nun bekannte Chiralitat von (+)-Zeaxanthin ((3R:3′R)-Dihydroxy-β,β-carotin) und von (+)-Xanthophyll ((3R:3′R)-Dihydroxy-β,ϵ-carotin) schliesst eine biologische Interconversion aus: sie wurde meso-Zeaxanthin ((3R:3′S)-Dihydroxy-β,β-carotin) ergeben. Es wird eine Hypothese fur die Hydroxylierung von - bzw. α-Carotin aufgestellt.

Synthesen der Nonactinsäure

Abstract: Two stereoselective syntheses of nonactic acid I, the building block of the macrotetrolide antibiotic nonactin are described. The characteristic cis-configuration of the 2,5-substituents on the tetrahydrofuran ring of I is obtained in the first synthesis by catalytic hydrogenation of the furan derivative X. This key intermediate possesses the carbon skeleton and correct distribution of oxygen functions for conversin into nonactic acid. It is synthesized by an electrophilic substitution of 2-acetonylfuran (VI) with the N-cyclohexyl-N-propenyl nitrosonium ion (V) generated from the corresponding α-chloronitrone (VII) and silver fluoroborate, followed by hydrolysis and oxidation of the aldehyde group. The second synthesis starts with a diol already having the correct configuration of the side chain that contains the hydroxyl group. For this purpose threo-1-octen-5,7-diol (XV) is synthesized from acetylacetone in two steps. Oxidative cleavage of the terminal double bond of this threo-diol yields an aldehyde which is converted by a Wittig reaction, with the carbanion, obtained from diethyl α-methoxycarbonylethyl phosphonate, into the open chain intermediate, 2-methyl-6,8-dihydroxy-2-nonenoic acid methylester (XVIII). Base-catalyzed cyclisation of this α,β-unsaturated dihydroxy ester yields the methyl ester of nonactic acid (I) as the main product.

Formation and Properties of Losod, a New Sodium Zeolite

Abstract: Losod, a new type of crystalline hydrated sodium aluminosilicate, Na12Al12Si12O48 · q H2O, has been prepared from reaction mixtures containing bulky quaternary alkylammonium ions, particularly azonia-spiro[4.4]nonane, besides sodium ions. Losod crystallizes from batches with a low sodium content (Na/Al ≤ 1 and Si/Al ≈ 1). The quaternary ammonium hydroxide primarily serves as a source of hydroxide ions and is not incorporated into the zeolite crystals. These bulky bases provide a useful means for controlling the alkalinity of the system independently of the concentration of the necessary cations built into the zeolite. The crystals of Losod are hexagonal (a = 12.91 and c = 10.54 A) and the proposed framework structure shows a polytypic relationship to sodalite and cancrinite. Losod has reversible sorption and ion exchange properties typical of a small-pore zeolite and in essential agreement with the proposed structure.

Selektive Synthesen mit Organometallen I. Konfigurativ einheitliche Folgeprodukte aus Alkenylkalium‐Zwischenstufen

Abstract: Me groups adjacent to an olefinic double bond were metalated by KOCMe3 and BuLi without cis-trans isomerization. Thus, (E)-MeCH:-CHMe was metalated to give (E)-MeCH:CHCH2K (I) which reacted with ethylene oxide to give 41% (E)-MeCH:CH(CH2)3OH. If I was allowed to equilibrate, the Z-isomer predominated (>99:1). Longer-chain olefins were metalated more slowly, with side reactions taking place. Thus, metalation of BuCH:CMe2 with EtCHMeBu and KOCMe3, followed by reaction with MeI gave 45% (Z)-BuCH:CMeEt, 9% BuCHMeCMe:CH2, and 19% Me(CH2)4CEt:CH2. [on SciFinder (R)]

Zur Identifikation potentieller Metabolite von Cannabis‐Inhaltstoffen: Kernresonanz‐ und massenspektroskopische Untersuchungen an seitenkettenhydroxylierten Cannabinoiden

Abstract: The 100-MHz-NMR-spectra of 11 side chain hydroxylated derivatives of cannabidiol (1), Δ6-tetrahydrocannabinol (2) and cannabinol (3) were analysed for signals specific for the position of hydroxyl groups. The mass spectra of these compounds and their trimethylsilyl ethers were investigated at ionisation voltages between 70 and 10 eV. The mass spectra of the non-silylated compounds showed no similarities independent on the basic type of cannabinoid but in the case of their trimethylsilyl ethers it was possible to derive fragmentations specific for the site of hydroxylation. These data are presented as a general method for the identification of small quantities of side chain hydroxylated in vitro and in vivo metabolites of cannabinoids.

Reaction Rates of t-Butyl and Pivaloyl Radicals in Solution

Abstract: The rate constants of the unimolecular decomposition of the pivaloyl radical (kD) and of the bimolecular self terminations of pivaloyl (k1) and t-butyl radicals (k2) in liquid methylcyclopentane are determined by ESR.-spectroscopy: The viscosity dependence of (k2) is analysed with respect to diffusion control of the reaction. Comparison of (kD) values of different acyl radicals reveals a strong dependence of the activation energies on radical structure.

Consequences of Substitution in the Photoelectron Spectra of [2, 2]Paracyclophanes: Separation of ‘through‐space’ and ‘through‐bond’ interactions as a consequence of fluorosubstitution

Abstract: The PE. spectra of [2, 2]paracyclophane (1), 4-amino[2, 2]paracyclophane (2) and 1, 1, 2, 2, 9, 9, 10, 10-octafluoro[2, 2]paracyclophane (3) are presented. The bands corresponding to ejection of the photoelectron from the five highest occupied π-orbitals have been assigned. The ‘observed’ orbital energies (i.e. the negative ionization potentials) are discussed in terms of ‘through space’ and ‘through-bond’ interactions between the semi-localized π-orbitals (e1g) of the benzene moieties and the C, C-σ-orbitals of the ethylene bridges. The PE. spectrum of 3 shows that the fluorine-induced lowering of the C, C-σ-orbital energy effectively ‘turns-off’ the ‘through-bond’ interaction. The resulting pattern of the first four bands confirms the assignment given for 1. Finally the band shifts induced by an amino group in position 4 are again in agreement with this assignment. Attention is drawn to the phenomenon of ‘orbital switching’ as a consequence of substitution in loosely coupled systems such as 1.

Metal Complexes with Macrocyclic Ligands, IV. Synthesis, Properties and Kinetics of Complexation with Three N‐methyl Substituted 1,4,8,11‐tetraazacyclotetradecanes

Abstract: The synthesis, properties and complexation of 1-methyl-1,4,8,11-tetraazacyclotetradecane (1-MeCyclam-14), 1,5-dimethyl-1,5,8,12-tetraazacyclotetradecane (2-MeCyclam-14) and 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane (4-MeCyclam-14) are described. While the Ni2+ and Cu2+ complexes of 1-MeCyclam-14 and 2-MeCyclam-14 exhibit square planar geometries, 4-MeCyclam-14 forms Ni2+ and Cu2+ complexes, whose absorption spectra are best explained by assuming pentaco-ordination of the metal ions. The complexation rate of the three N-methyl substituted macrocycles with Cu2+ and Ni2+ is slower than can be accounted for by water exchange and little affected by introducing methyl groups at the nitrogens. Both results are in contrast to what is known for open chain amine ligands. A mechanism for the complexation is proposed, which also explains why the products of the reaction of 4-MeCyclam-14 with Cu2+ and Ni2+ are pentaco-ordinated.

Regiospecific Acylation, Alkylation, and Aldol Condensation using magnesium enolates resulting from the conjugate addition of grignard reagents to α, β-unsaturated ketones

Abstract: The magnesium 3,3-dimethylcyclohex-1-enolate 1i, formed in the copper catalyzed addition of methylmagnesium iodide to 3-methylcyclohex-2-enone, has been subjected to regiospecific electrophilic reactions such as acylation, alkylation, and aldol condensation in order to find a new access to the damascones, ionones and carotenoids. By way of illustration a new synthesis of γ-damascone is described.

Comparison of 13C‐ and 1H‐Magnetic Resonance Spectroscopy as Techniques for the Quantitative Investigation of Dynamic Processes. The cope rearrangement in bullvalene

Abstract: The potential advantages of 13C-(1H-noise decoupled) spectroscopy (in the Fourier transform mode) over 1H-spectroscopy for the quantitative investigation of molecular dynamic process is discussed. The Cope rearrangement in bullvalene, an example of complex exchange of spins over different magnetic sites, has been studied by both kinds of spectroscopy as a test.

The Reaction of some Carbonyl and Thiocarbonyl Compounds with Prenyl‐ and Crotyllithium in Tetrahydrofuran Solution

Abstract: Prenyllithium (3-methylbut-2-enyl-lithium) (1) and cis-crotyllithium (Z-but-2-enyl-lithium) (2) in tetrahydrofuran solution, prepared according to the method of Eisch & Jacobs, react with carbonyl compounds to give the branched alcoholates with moderate to high selectivity, unless access to the carbonyl group is strongly hindered (see the Table). Adamantanethione (12) reacts with 1 to give the unbranched thiolate.

Vitamin D3 Metabolites II. Further Syntheses of 25-Hydroxycholesterol†

Abstract: Zwei weitere Synthesen von 25-Hydroxycholesterin (10) ausgehend von Pregnenolon (1) bzw. O-acetylpregnenolon (13) werden beschrieben. Dabei wird jedesmal auch das noch unbekannte 20(S)-25-Hydroxycholesterin (11) erhalten. Fernerhin wird ein Zusammenhang zwischen der chemischen Verschiebung der NMR.-Signale der C(21)-Methylgruppe und der Stereochemie am C(20) festgestellt.

Hyperfine Shifts of the 13C‐NMR. in Protoporphyrin IX Iron (III) Dicyanide and Deuteroporphyrin IX Iron (III) Dicyanide

Abstract: The 13C-NMR. in Zn(II) (Protoporphyrin IX), Fe(III) (Protoporphrin IX) (CN)2, Zn(II) (Deuteroporphyrin IX dimethylester), and Fe(III) (Deuteroporphyrin IX) (CN)2 have been identified, and the 13C hyperfine shifts in the iron complexes evaluated. In a partial analysis of these data the parameters QH, QCCHH, and QC′CHC, which characterize the isotropic coupling through hyperconjugation between the 1H and 13C nuclei of the porphyrin side chains and the unpaired electron spin density on the aromatic ring carbon atoms, have been re-examined. This paper is part of an investigation of the electronic states in low spin ferric hemes and hemoproteins, and the relations between the electronic structures and the biological roles of these molecules.

The crystal structure of the NaNCS complex of nonactin.

Abstract: The NaNCS complex of the macrotetrolide antibiotic nonactin, which acts as an ionophore with biological and artificial membranes crystallizes in the space group C2/c, a = 15.55, b = 19.59, c = 15.31 A, β = 90°. The X-ray crystal structure investigation shows that Na+ is coordinated by four carbonyl oxygen atoms (Na+ … O, 2.42 A) and four ether oxygen atoms (Na+ … O, 2.77 A). The cubic coordination by eight equidistant oxygen atoms observed in the K+ complex (K+ … O, 2.81 A) is thus deformed. This, however, requires only very small changes in the ligand conformation.

Photoelectron Spectroscopy of peri‐Amino Naphthalenes

Abstract: The He I photoelectron spectra of peri-amino and dimethylamino naphthalenes are presented. The differences in the ionization energies of the π-bands are interpreted by separation of the perturbation of the amino substituent into an inductive destabilization and conjugative stabilization. This affords the assignment of the photoelectron bands of ionization energies below 11 eV and an estimation of the dihedral angle in the peri-dimethylamino derivatives. The data on the peri-amino naphthalenes indicate some angular distortion in contrast to 2-aminonaphthalene.

Photochemische Primärreaktionen α-verzweigter aliphatischer Ketone und Aldehyde in lösung

Abstract: UV.-Irradiation of methyl t-butyl ketone, di-t-butyl ketone, pivalaldehyde and isobutyraldehyde in benzene solution leads to chemically induced dynamic nuclear polarization (CIDNP.) of the parent compounds and of various reaction products. CIDNP.-effects and product distributions establish type I α-cleavage predominantly of triplet state molecules as the major primary photochemical step for all the four α-branched carbonyl compounds. In chlorinated solvents singlet reactions interfere with the triplet processes.

Dielectric Properties of Apolar Micelle Solutions Containing Solubilized Water

Abstract: Varying amounts of water have been solubilized in a micelle solution of sodium di-2-pentyl–sulfoscuccinate in benzene and the complex permittivity has been observed in the range 200 KHz to 10 MHz. Part of a dielectric dispersion is seen, which extends to higher frequencies with a broad distribution of relaxation times. Due to association processes, the static dielectric increment is found to vary non-linearly with hydrated micelle concentration and with the amount of solubilized water, whereas a linear variation with micelle concentration is found if no water is added. These effects are explained on the assumption that part of the solubilized water increases the dipole moment of the micelle. Additionally, at higher water concentrations, a sudden increase in the conductivity of the solution is observed, which is taken to indicate a conformational change of the solubilized micelle.

Metal Complexes with Macrocyclic Ligands, V. Formation and dissociation kinetics of the pentaco‐ordinated Ni2+, Cu2+, Co2+ and Zn2+ complexes with 1,4,8,11‐tetramethyl‐1,4,8,11‐tetraazacyclotetradecane

Abstract: The formation and dissociation kinetics of the pentaco-ordinated Cu2+, Ni2+, Co2+ and Zn2+ complexes with 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane (4-MeCyclam-14) was studied by pH-stat techniques and spectrophotometrically. The rates of the reactions between 4-MeCyclam-14 and each of the four metal ions, although slower than normal complexations by a factor of 103−104, closely follow the order Cu2+ > Zn2+ > Co2+ > Ni2+, found for the rate of water exchange. This implies that beside water exchange an other constant factor plays an important role in the rate determing step. The dissociation of the pentaco-ordinated 4-MeCyclam-14 complexes is acid catalyzed. The limiting rate for acid dissociation is not reached even in 2.5M HNO3 in the case of Ni(4-MeCyclam-14)2+. From the formation and dissociation rates stability constants have been calculated, which do not show any macrocyclic effect.

Terpenoids Derived from Linalyl Oxide. Part 1. The stereochemistry of the davanones

Abstract: Natural (+)-davanone is 6S,7S,10R-2,6,10-trimethyl-7,10-oxidododeca-2,11-dien-5-one (1). Equilibration of davanone with base leads to the four possible isomers, but only a single deuterium atom is exchanged when deuterium oxide is the solvent.

The Gas‐Solid Interface Calculations of Adsorption Potentials in Slot‐Like Pores of Molecular Dimensions

Abstract: Two theoretical models are presented for the calculation of adsorption potentials in slot-like pores of molecular dimensions, with respect to the adsorption by a single flat surface. The cases of continuous and layer-like solids are considered, with interatomic pair-potentials of the 6:12 type, and for pore widths ranging from two to four times the equilibrium distance of adsorption. Both models give good results for the adsorption of simple molecules by microporous carbons and graphitized carbon blacks.