Determination of the Relative Configurations in the Side Chains of the Antibiotics Hedamycin and Pluramycin A; Synthesis and NMR. Data of Suitable Model Compounds

Several diepoxyhexanoates and epoxyhexenoates were prepared by epoxidation of methyl 2-methyl-2,4-hexadienoate or by Darzens condensation. Their ¹ H- and ¹³C-NMR. spectra were measured and assigned. Comparison of these data with the spectra of the antibiotics hedamycin ( 1 ) and pluramycin A ( 2 ) allowed the determi-nation of the relative configurations in the side chains of these antibiotics. They were found to be (14R*,16S*,17R*,18S*) for hedamycin ( 1 ) and (14R*,16S*,17Z) for pluramycin A ( 2 ).     

A structural investigation of the antibiotic rubiflavin. Preliminary communication

Rubiflavin is shown to be a mixture of antibiotics. The main components have been named rubiflavin A (3) and rubiflavin B (2) and are identified by NMR. spectroscopy as desacetylpluramycin A and kidamycin, respectively.     

Investigation of benzimidazoles. III—transmission of the substituent effects in 2-substituted 1-methylbenzimidazoles studied by 13C nuclear magnetic resonance

The influence of substituents on the ¹³C NMR chemical shifts of 2-substituted 1-methylbenzimidazoles has been investigated. The electronic effects of the substituents are transmitted to C-4 and C-7 mainly by the resonance mechanism, and to C-5, C-6 and N-CH₃, by approximately equal contributions of the resonance and inductive components. A critical analysis of the share in the transmission of substituent effects through the ‘pyridine-type’ and ‘pyrrole-type’ nitrogen atoms is given.     

Die massenspektrometrische Fragmentierung von Neopentylpolyolestern. 1—Pentaerythrittetrafettsäureester

The fragmentation of the homologous fatty acid tetraesters of pentaerythritol (C-2 to C-14) upon electron impact was investigated. The main fragment ions are [M? RCOO]⁺ and [M? RCOOH]⁺, for which cyclic acetal structures are postulated. Subsequent fragmentation was elucidated by ‘direct analysis of daughter ion’ (DADI) measurements and high resolution measurements. Esters of branched fatty acids can be distinguished from esters of n-fatty acids by characteristic ions. Isomeric esters of n-fatty acids cannot be separated by gas chromatography but identification is also possible by mass spectrometry.     

Übergangsmetallkomplexe mit Schwefelliganden. XLIV. Ruthenium(II)-Komplexe mit dem sterisch anspruchsvollen Thioether-Thiolat-Liganden ‚buS4’︁2− (= 1,2-Bis(3,5-di(tertiärbutyl)-2-mercaptophenylthio)-ethan (2-)) sowie den Koliganden PPh3, PMe3, CO,NH3 und N2H4

Transition Metal Complexes with Sulfur Ligands. XLIV. Ruthenium(II) Complexes with the Sterically Demanding Thioether-thiolate Ligand ?^buS₄’?^2?(= 1,2-Bis(3,5-di(tertiarybutyl)-2-mercaptophenylthio) ethane (2-)) and PPh₃, CO, PMe₃, NH₃, and N₂H₄ Coligands The coordination properties of the sterically demanding thioether-thiolate ligand ‘^buS₄’^2? (= 1,2-Bis(3,5-di(tertiarybutyl)-2-mercaptophenylthio)ethane (2-)) towards Ruthenium were investigated. [Ru(PPh₃)₂ (‘^buS₄’)], 1 , was obtained from [RuCl₂(PPh₃)₃] and ‘^buS₄’? Li₂. One PPh₃ ligand in 1 is labile towards substitution and can be exchanged by L ? CO ( 2 ), PMe₃ ( 3 ), or NH₃ ( 5 ) yielding [Ru(L)(PPh₃)(‘^buS₄’)]. The PMe₃ complex [Ru(PMe₃)₂(‘^buS₄’)], 4 , is thermically inert as well as 2, 3 , and [Ru(CO)₂(‘^buS₄’)], 6 , which was obtained from [RuCl₂(CO)₃THF] and ‘^buS₄’? Li₂. Considering the thermical reaction inertness of 6 , its fast reaction with N₂H₄ yielding [Ru(N₂H₄) (CO) (‘^buS₄’)], 7 , is remarkable; the reaction probably takes place via 19e- intermediates. All ‘^buS₄’ complexes are better soluble in organic solvents than the corresponding [Ru(‘S₄’)] parent compounds, their ν(CO)frequencies or ³¹PNMR shifts, however, are nearly identical, allowing the conclusion that the influence of the t-butyl groups is topological and not electronic. All now complexes were characterized by elemental analyses as well as IR, NMR, and mass spectroscopy.     

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

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 ( e_1g ) 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 .     

Conformational Features of 7,8,13β,14α-Tetrahydro-N7-methylcorysaminium,a biosynthetic intermediate to the protopine-type alkaloid corycavine

The crystal structure of (±)-7,8,13β,14α-tetrahydro-N⁷-(¹³C)methylcorysaminium iodide (¹³C- 3a ·I) was investigated by X-ray analysis and thus the relative configuration (7S*,13S*,14S*) established (Fig. 1). The conformation of 3a was shown to have a cis-junction of the B/C rings and the rings A and D in an antiperiplanar position relative to the C(13)? C(14) bond (‘anti-cis’), a twisted half-chair for ring B, and a half-chair for ring C (Figs. 2 and 3). Conformation analysis by ¹H-NMR data indicated that the crystal conformation of 3a is also the preferred one in MeOH solution.     

Theoretical Study of Structural Relationships and Electrochemical Properties of Supramolecular [14-MR Macrolides]@Cn Complexes

Macrolides are a broad spectrum of antibiotics that are commonly used in human pathologies as well as in veterinary medicine. The electrochemical detection of macrolide antibiotics were studied at various methods using amperometric and coulometric detectors. Since the discovery of fullerenes (C_n), one of the main classes of carbon compounds, the unusual structures and physiochemical properties of these molecules have been discovered, and many potential applications and physicochemical properties have been introduced. Up to now, various empty carbon fullerenes with different numbers “n,” such as C₆₀, C₇₀, C₇₆, C₈₂, and C₈₆, have been obtained. Topological indices are digital values that are assigned based on chemical composition. These values are purported to correlate chemical structures with various chemical and physical properties. They have been successfully used to construct effective and useful mathematical methods to establish clear relationships between structural data and the physical properties of these materials. In this study, the number of carbon atoms in the fullerenes was used as an index to establish a relationship between the structures of Erythromycin-A (EA), Erythromycin-A enol ether (EMEN), Olendomycin (OM), and Anhydroerythromycin-A (AEA), 1-4 and fullerenes C_n (n = 60, 70, 76, 82 and 86), which create [Tetracyclines]@C_n, A-1 to A-5 ([EA]@C_n), B-1 to B-5 ([EMEN]@C_n), C-1 to C-5 ([OM]@C_n), and D-1 to D-5 ([AEA]@C_n). The relationship between the number of carbon atoms and the free energies of electron transfer (ΔG_et(1) to ΔG_et(4)) is assessed using the Rehm-Weller equation for A-1 to A-5, B1 to B-5, C-1 to C-5, and D-1 to D-5 supramolecular [14-MR Macrolides]@C_n complexes 5-24. Calculations are presented for the four reduction potentials (^Red.E₁ to ^Red.E₄) of fullerenes C _n . The results were used to calculate the four free-energies of electron transfer (ΔG_et(1) to ΔG_et(4)) of supramolecular complexes A-1 to A-18 to B-1 to B-18, C-1 to C-18, and D-1 to D-18 (5-76) for fullerenes C₆₀ to C₃₀₀.     

Säure-Additionen an ‘Push-Pull’-Enine. Erste Beobachtung einer Umlagerung von 5-Chloro-5-(dialkylamino)pentadienalen

Reaction of ‘Push-Pull’ Enynes with Acids. First Observation of a Rearrangement of 5-Chloro-5-(dialkylamino)pentadienals ‘Push-pull’-enynes 7 react easily with HCl as well as with AcOH to give 5-amino-5-chloropentadienals 8 and 5-(acetoxy)-5-aminopentadienals 13 as well as the corresponding ketones. In view of a postulated rearrangement of compounds 8 and 13 (Scheme 2), both types of compounds have been treated with traces of acid. While no definite reaction is observed in case of 13 , HCl-addition products 8 easily and quantitatively rearrange to give 2H-pyran-2-iminium chlorides 10 which are the postulated intermediates of the rearrangement 8 → 12 (Scheme 2).     

Analogs of Cinchona Alkaloids Incorporating a 9,9′-Spirobifluorene Moiety

The Cinchona alkaloid analogs (+)- and (?)- 5 with a quinuclidine-2-methanol residue attached to C(2) of a 9,9′-spirobifluorene moiety were prepared as a racemic mixture by reacting lithiated 2-bromo-9,9′-spirobifluorene 7 with (2-ethoxycarbonyl)quinuclidine (±)- 6 to give ketone (±)- 8 , followed by diastereoselective reduction with diisobutylaluminum hydride (DIBAL-H). The absolute configuration at C(9) and C(8), i.e., at the methanol bridge and the adjacent quinuclidine C-atom, in the two enantiomers of 5 is identical to the configuration at the corresponding centers in (?)-quinine ( 1 ) and (+)-quinidine ( 2 ), respectively. For the optical resolution of (±)- 5 , a chiral stationary phase for HPLC was prepared by covalently bonding quinine via a thiol spacer to a silica-gel surface. The enantiomer separation was accomplished at an α value of 1.61 with (±)- 5 being eluted last, in agreement with ¹H-NMR studies in CDCl₃ which showed that (+)- 5 underwent a more stable host-guest association with quinine than (?)- 5 . ¹H{¹H} Nuclear Overhauser effect (NOE) difference spectroscopical analysis of the host-guest associations with quinine in CDCl₃, combined with computer-model examinations, allowed the assignment of the absolute configurations as (+)-(8R,9S)- 5 and (?)-(8S,9R)- 5 . A detailed conformational analysis displayed excellent agreement between the results of computational methods (Monte Carlo multiple minimum simulations, analyses of the total energy as a function of the flexible dihedral angles in the molecule) and ¹H{¹H}-NOE difference spectroscopical data. It was found that (?)- 5 and (+)- 5 differ significantly in their conformational preference from their natural counterparts quinine ( 1 ) and quinidine ( 2 ). Whereas the natural alkaloids prefer the ‘open’ conformation, with the quinuclidine N-atom pointing away from the quinoline ring, analog (±)- 5 adopts preferentially (by ca. 4 kcal mol^?1) a ‘closed’ conformation, in which the quinuclidine N-atom points into the cleft of the 9,9′-spirobifluorene moiety. Since the basic quinuclidine N-atom in the ‘closed’ conformation is sterically shielded from forming strong H-bonds, the new Cinchona alkaloid analogs form less stable host-guest associations via H-bonding than quinine or quinidine.     

Versuche zur Herstellung eines «Bis(triasterans)» und Synthese des heterocyclischen (Tricyclo[4.4.1.01,6]undeca-3,8-dien-11,11-dimethyl)sulfits

Tentative Synthesis of ‘Bis(triasterane)’ and Synthesis of the Heterocyclic (Tricyclo[4.4.1.0^1,6]undeca-3,8-diene-11,11-dimethyl)sulfite The synthesis of the bis(triasterane) ( 1 ) has been tried; the reaction of ‘isotetraline’ (1,4,5,8-Tetrahydronaphthalene; 2 ) with diazomalonate yielded the tricyclic systems 5 and 6 , and not 4 . Hydrolysis of 5 gave the monocarboxylic acid 7 , and not the dicarboxylic acid 9 . The latter could be obtained from the dibromoderivative 8 , but 9 couldn't be converted to the acyl chloride 10 . The reduction of 9 with LiAlH₄ yielded the crystalline diol 11 , which was cyclized with SOCl₂ to the heterocycle 12 . The spectral data of the new compounds 5, 6, 7, 11 and 12 are reported and discussed.     

Recent Developments in Electroanalytical Chemistry of Cephalosporins and Cefamycins

Cephalosporins (I, R⁴ = H) and cefamycins (I, R⁴ = OCH₃) are antibiotics with a broad spectrum of antimicrobial and antibacterial properties. These compounds contain a β-lactam ring which is fused with a six-membered dihydrothiazine ring bearing substituents R¹ and R² in the side-chains at C-3 and C-7 (I)(Table I).     

‘Click Synthesis’ of Some Novel Benzimidazol Oxime Ethers Containing Heterocycle Residues as Potential ß‐Adrenergic Blocking Agents

The ‘click synthesis’ of some novel O‐substituted oximes, 5a – 5j , which contain heterocycle residues, as new analogs of ß‐adrenoceptor antagonists is described (Scheme 1). The synthesis of these compounds was achieved in four steps. The formation of (E)‐2‐(1H‐benzo[d]imidazol‐1‐yl)‐1‐phenylethanone oxime, followed by their reaction with 2‐(chloromethyl)oxirane, afforded mixture of oil compounds 3 and 4 , which by a subsequent tetra‐n‐butylammonium bromide (TBAB)‐catalyzed reaction with N H heterocycle compounds (Scheme 1), led to the target compounds 5a – 5j in good yields.     

α-D-Glycosyl-Substituted α,α-D-Trehaloses with (1 → 4)-Linkage: Syntheses and NMR Investigations

Two symmetrical trehalose glycosyl ‘acceptors’ 4 and 6 were prepared and three of the unsymmetrical type, 8 , 10 , and 11 . Glucosylation of symmetrical ‘acceptor’ 4 gave a higher yield of trisaccharide (44%) than protect ve-group manipulation, namely via selective debenzylidenation 2 → 9 or monoacetylation 2 → 5 which proceeded in moderate yields (33–34%). A comparison of catalysts in the cis-glucosylation of trehalose ‘acceptor’ 10 with tetra-O-benzyl-β-D -glucopyranosyl fluoride 13 profiled triflic anhydride ((Tf)₂O) as a new reactive promoter yielding 92% of trisaccharide 14 , deblocking gave the target saccharide α-D -glucopyranosyI-( 1 → 4 )-α,α-D -trehalose. ¹H-NMR spectra of most compounds were analyzed extensively. The use of the ID TOCSY technique is advocated for its time efficiency, if needed supplemented by ROESY experiments.     

Structural and Configurational Dependence of the Sensory Process in Steroids

Structural modifications of testosterone and 19-nortestosterone have led to the synthesis of over 60 androstane and estrane derivatives whose sensory evaluation has allowed molecular parameters to be established for release of a ‘steroid-type’ scent. Odor perception with O-containing compounds in both classes has been found to be regioselective . Osmophoric groups at C(3) were found to be the most active and specific. Functionality at C(2) is accompanied to a large extent by anosmic defects, and O-containing substituents at C(1) and C(4) appear to affect the receptor membrane in exceptional cases. A further characteristic of the ‘steroid-type’ scent is diastereoselectivity. The odor intensity of axial 2- and 3-hydroxysteroids is far greater than that of the equatorial epimers, and epimeric hydroxy-groups in the 1-, 4-, and 5-positions lead to almost complete absence of odor. In addition, only steroids with ‘normal’ ring junctions and configuration were found to be odorants, whereas compounds with cis-junctions between rings A and B, or C and D, were found to be practically inactive, Steroids therefore folow the ‘triaxial rule of odor sensation’. The most remarkable feature of our findings with steroid odorants is enantioselectivity

1 The term ‘regioselective’ is currently used for a reaction in which formation of one structural (or positional) isomer is favored over another. For convenience we use ‘regioselective’, ‘diastereoselective’ or ‘enantioselective’ for substrate-receptor interactions in which one positional isomer, diastereoisomer or enantiomer leads to a different sensory response (in quality and/or intensity) than another.

. Whereas with C ₁₉ -steroids of the ‘natural’ enantiomeric series the perception threshold is extremely low (<6 ppb), the corresponding ‘unnatural’ enantiomers have been found essentially odorless by a panel of 30 persons. This appears to be the first reported instance of a total enantioselective response to an odorant.     

Site‐Directed Spin‐Labeling of DNA by the Azide–Alkyne ‘Click’ Reaction: Nanometer Distance Measurements on 7‐Deaza‐2′‐deoxyadenosine and 2′‐Deoxyuridine Nitroxide Conjugates Spatially Separated or Linked to a ‘dA‐dT’ Base Pair

Nucleobase‐directed spin‐labeling by the azide‐alkyne ‘click’ (CuAAC) reaction has been performed for the first time with oligonucleotides. 7‐Deaza‐7‐ethynyl‐2′‐deoxyadenosine ( 1 ) and 5‐ethynyl‐2′‐deoxyuridine ( 2 ) were chosen to incorporate terminal triple bonds into DNA. Oligonucleotides containing 1 or 2 were synthesized on a solid phase and spin labeling with 4‐azido‐2,2,6,6‐tetramethylpiperidine 1‐oxyl (4‐azido‐TEMPO, 3 ) was performed by post‐modification in solution. Two spin labels ( 3 ) were incorporated with high efficiency into the DNA duplex at spatially separated positions or into a ‘dA‐dT’ base pair. Modification at the 5‐position of the pyrimidine base or at the 7‐position of the 7‐deazapurine residue gave steric freedom to the spin label in the major groove of duplex DNA. By applying cw and pulse EPR spectroscopy, very accurate distances between spin labels, within the range of 1–2 nm, were measured. The spin–spin distance was 1.8±0.2 nm for DNA duplex 17 ( dA*^7,10 ) ?11 containing two spin labels that are separated by two nucleotides within one individual strand. A distance of 1.4±0.2 nm was found for the spin‐labeled ‘dA‐dT’ base pair 15 ( dA*⁷ ) ?16 ( dT*⁶ ). The ‘click’ approach has the potential to be applied to all four constituents of DNA, which indicates the universal applicability of the method. New insights into the structural changes of canonical or modified DNA are expected to provide additional information on novel DNA structures, protein interaction, DNA architecture, and synthetic biology.     

Synthesis of the Pluramycins 1: Two Designed Anthrones as Enabling Platforms for Flexible Bis‐C‐Glycosylation

Two effective tricyclic platforms are reported for the installation of the two constituent sugars, L ‐vancosamine and D ‐angolosamine, in a regio‐ and stereoselective manner for the synthesis of the pluramycin class of bis‐C‐glycoside antitumor antibiotics. Two complementary protocols are now available that differ in the order in which the two sugar moieties are installed. Sc(OTf)₃ was effective as the Lewis acid.     

Conformational Studies of Marine Polyhalogenated α-Chamigrenes Using Temperature-dependent NMR spectra inverted-chair and twist-boat cyclohexane moieties in the presence of an axial halogen atom at C(8)

α-Chamigren-3-one (+) -8 bearing an axial CI-atom at C(8) exists as a largely dominant conformer with Me—C(5) at the envelope-shaped enone ring pointing away from CI_ax?C(8) at the cyclohexane ring (= B) in the ‘normal’ chair conformation, as shown by ¹H-NMR. In contrast, the α-chamigren-3-ols (+) -9 and (+) -10 , obtained from hydride reduction of (+) -8 , show a temperature-dependent equilibrium of conformers where the major conformers have ring B in the inverted-chair (and twist-boat for (+) -9 ) conformation to avoid repulsions between Me?C(5) and CI_ax–C(8) (Scheme 1). This is in agreement with the conformation of the epoxidation product (+) -12 of (+) -9 where Me–C(5) is pushed away from CI_ax–C(8) in a ring-B chair similar to that of (+) -8 (Scheme 2). Introduction of a pseudoequatorial Br-atom at C(2) of (+) -8 , as in enone (+) -15 (Scheme 3), does not affect the conformation; but a pseudoaxial Br? C(2) experiences repulsive interactions with H_eq–C(7), as shown by the ¹H-NMR data of the isomeric enone (+) -16 where the ‘normal’-chair conformer Cβ -16 is in an equilibrium with the inverted chair conformer ICβ -16 (Scheme 3). These results and the accompanying paper allow a unifying view on the conformational behavior of marine polyhalogenated α-chamigrenes. This view is supported by the acid-induced isomerization of α-chamigrene (+) -9 (inverted chair) to β-chamigrene (+) -17 (‘normal’ chair; Scheme 4), the driving force being the lesser space requirement of CH₂?C(5) than of Me–C(5). This explains why β-chamigrenes are so common in nature.     

Utilisation d'ylides du phosphore en chimie des sucres. XII Dérivés du D-arabino-hexène-1-tétrol-3,4,5,6

The preparation of several kinds of derivatives of 1-substituted D -arabinc-hex-1-ene-3,4,5,6-tetrols is described. Some of these compounds, having a ‘pseudo-formyl’ group (? CH?CHCN, ? CH?CHSO₂CH₃) are ‘pseudo-aldehydo-sugars’. Their ability to react as aldehydo-sugars was examined in light of their ¹³C-NMR. spectra which provide information on their electron density at C(1) and C(2).     

Biotransformation of (+)-isofraxinellone by Aspergillus niger and insect antifeedant activity

The biotransformation of (+)-isofraxinellone (1) by Aspergillus niger was investigated. Compound 1 was transformed to only one new compound 2. The structure of 2 was identified as (-)-(4S)-4-hydroxyisofraxinellone which was regio- and stereo-selective hydroxylated at the C-4 position by IR, EI-MS 1D and 2D NMR. Absolute configuration of hydroxyl group at the C-4 position was detected by modified Mosher’s method. Antifeedant activity of compounds 1 and 2 against larvae of Spodoptera litura was assayed. These compounds showed potent antifeedant activity and ED₅₀ (50% of effective dose) values were 3.91 and 4.43 μg/cm², respectively.