Showing papers in "Helvetica Chimica Acta in 1993"

Improved purification of C60 and formation of σ- and π-homoaromatic methano-bridged fullerenes by reaction with alkyl diazoacetates

Abstract: A rapid and inexpensive method for the large-scale purification of C60 is the simple filtration of the toluenesoluble extract of commercial fullerene soot through a short plug of charcoal/silica gel with toluene as the eluent. Reactions of C60 with ethyl and tert-butyl diazoacetates in refluxing toluene lead to the formation of the (alkoxycarbonyl)methylene-bridged isomers 1a–3a and 1b–3b, respectively, which can be equilibrated, upon further heating, into the single compounds 1a and 1b, respectively. Isomers 1a/b possess the methano bridge at the 6–6 ring junction, whereas structures 2a/b and 3a/b are bridged at the 6–5 junction. A dramatic influence of local and π-ring current anisotropic effects of the fullerene sphere on the NMR chemical shifts of the methine protons in the bridge is observed: the chemical shifts of the protons located over a pentagon ring in 2a/b and over a hexagon ring in 3a/b differ by Δδ = 3.47 and 3.45 ppm, respectively. The analysis of the 13C-NMR chemical shifts of the bridgehead C-atoms and the 1J(C,H) coupling constants for the methano-bridge atoms reveals conclusively that the 6-5-ring-bridged structures 2a/2b and 3a/3b are π-homoaromatic (‘open’ transannular bond) and the 6-6-ring-bridged structures 1a/b are π-homoaromatic (‘closed’ transannular bond). The electronic absorption spectra show that π-homoconjugation in 2a/b and 3a/b represents a much smaller electronic perturbation of the original C60 chromophore than σ-homoconjugation in 1a/b. The results of this study demonstrate an impressive linkage between the chemistry of methano-bridged annulenes and methano-bridged fullerenes.

Development of Luminescent Europium(III) and Terbium(III) chelates of 2,2′:6′,2″‐ terpyridine derivatives for protein labelling

Abstract: The synthesis and luminescence properties are reported for 20 different chelates composed of 2,2′:6′,2″-terpyridine as the energy-absorbing and donating group, EuIIIand TbIII as the emitting ions, methylenenitrilo(acetic acids) as the stabel chelate-forming moieties, and isothiocyanato or(4,6-dichloro-1,3,5-triazin-2-yl)amino groups as the activated moieties for coupling to biomolecules.

Synthesis of a Fullerene Derivative of Benzo[18]crown‐6 by Diels‐Alder Reaction: Complexation Ability, Amphiphilic Properties, and X‐Ray Crystal Structure of a Dimethoxy‐1,9‐(methano[1,2]benzenomethano)fullerene[60] Benzene Clathrate

Abstract: A fullerene derivative 1 of benzo[18]crown-6 was obtained by Diels-Alder addition of fullerene[60](C60) to the ortho-quinodimethane prepared in situ from 4,5-bis(bromomethyl)benzo[18]crown-6 (3) with Bu4NI in toluene. Extraction experiments show that the complexation of K+ ions strongly increases the solubility of 1 in protic solvents like MeOH. Using Langmuir-Blodgett techniques, monolayers of the highly amphiphilic fullerene-derived crown ether 1 and its K+ ion complex were prepared. An X-ray crystal structure was obtained from a benzene clathrate of comparison compound 2, synthesized by Diels-Alder reaction of C60 with the ortho-quinodimethane derived from 1,2-bis(bromomethyl)-4,5-dimethoxybenzene (4). Both the fullerene molecule 2 and the benzene molecule are fully ordered in a crystal packing which is stabilized by intermolecular van-der-Waals contacts between the benzene ring and the C-spheres, intermolecular C…C contacts between the C60 moieties, and intermolecular O…C contacts between the O-atoms of the veratrole moieties and fullerene C-atoms.

Why Pentose‐ and Not Hexose‐Nucleic Acids??. Part VII. Pyranosyl‐RNA (‘p‐RNA’). Preliminary communication

Abstract: A review with 39 refs. Qual. conformational anal. of the entirety of conceivable hexo- and pentopyranosyl oligonucleotide systems derived from the diastereoisomeric aldohexoses (CH2O)6 and aldopentoses (CH2O)5 predicts the existence of a variety of pairing systems which have not been exptl. investigated so far. In particular, the anal. foresees the existence of a ribopyranosyl isomer of RNA ('p-RNA'), contg. the phosphodiester linkage between the positions C(4') and C(2') of neighboring ribopyranosyl units. Double strands of p-RNA oligonucleotides are expected to have a linear structure and to show purine-pyrimidine and purine-purine (Watson-Crick) pairing comparable in strength to that obsd. in homo-DNA. Exptl., synthetic b-D-ribopyranosyl (4'->2')-oligonucleotides derived from adenine and uracil confirm this prognosis: adenine-uracil pairing in p-RNA duplexes is stronger than in the corresponding RNA duplexes. Importantly, adenine in p-Ribo(A8) does not show (reverse-Hoogsteen) self-pairing, in sharp contrast to its behavior in the homo-DNA series. The sheer existence of strong and selective pairing in a system that is constitutionally isomeric to RNA and can be predicted to have a linear structure has implications for the problem of RNA's origin. In this context, a comprehensive exptl. study of the pairing properties of p-RNA, of its potential for constitutional assembly, self-replication, and intra-duplex isomerization to RNA seems mandatory. [on SciFinder (R)]

Nucleic‐Acid Analogues with Constraint Conformational Flexibility in the Sugar‐Phosphate Backbone (‘Bicyclo‐DNA’). Part 1. Preparation of (3S,5′R)‐2′‐Deoxy‐3′,5′‐ethano‐αβ‐D‐ribonucleosides (‘Bicyclonucleosides’)

Abstract: We describe the synthesis of 2′-deoxy-3′,5′-ethano-D-ribonucleosides 1–8 (= (5′,8′-dihydroxy-2′-oxabicyclo-[3.3.0]oct-3′-yl)purines or -pyrimidines) of the nucleobases adenine, thymine, cytosine, and guanine. They differ from natural 2′-deoxyribonucleosides only by an additional ethylene bridge between the centers C(3′) and C(5′). The configuration at these centers (3S,5′R) was chosen as to match the geometry of a repeating nucleoside unit in duplex DNA as close as possible. These nucleosides were designed to confer, as constituents of an oligonucleotide chain, a higher degree of preorganization of a single strand for duplex formation with respect to natural DNA, thus leading to an entropic advantage for the pairing process. The synthesis of these ‘bicyclonucleosides’ was achieved by construction of an enantiomerically pure carbohydrate precursor 18/19 (Schemes 1), which was then converted to the corresponding nucleosides by known methods in nucleoside synthesis (Schemes 2 and 3). In all cases, both anomeric forms of the nucleosides were obtained in pure crystalline form, the relative configuration of which was established by 1H-NMR-NOE spectroscopy. A conformational analysis of the nucleosides with β-configuration at the anomeric center by means of X-ray and 1H-NMR (including NOE) spectroscopy show the furanose part of the molecules to adopt uniformly a 1′exo-conformation with the base substituents preferentially in the anti-range in the pyrimidine nucleosides (anti/syn ca. 2:1) distribution in the purine nucleosides (in solution).

Structures and Chemistry of Methanofullerenes: A Versatile Route into N-[(Methanofullerene)carbonyl]-Substituted Amino Acids

Abstract: The reaction of C60 with oxadiazole 13 afforded the dimethoxymethanofullerene 7 in 32% yield as a 6-6-ring-bridged isomer with a closed transannular bond. A literature survey showed that all 6-6-ring-bridged methanofullerenes are σ-homoaromatic with a closed transannular bond (6-6-closed) and all 6-5-ring-bridged are π-homoaromatic with an open transannular bond (6-5-open). The preference for 6-6-closed and 6-5-open structures is not due to substituent effects but is best explained with the conservation in these isomers of the favorable bonding seen in C60 with higher double-bond character at 6-6 bonds and higher single-bond character at 6-5 bonds. Reaction of C60 with diazo diester 15 gave the fullerene diester 14 which was hydrolyzed with BBr3 in benzene to the methanofullerenecarboxylic acid 10, a versatile synthon for the preparation of amphiphilic fullerene derivatives. Treatment of 10 with alcohols and amino acid esters under DCC coupling conditions afforded the esters 5 and 17 and the amino-acid derivatives 11 and 12, respectively.

Warum pentose-und nicht hexose-nucleinsäuren? Teil III. Oligo(2′,3′-dideoxy-β-D-glucopyranosyl) nucleotide (‘homo-DNS’): Paarungesigenschaften†‡

Abstract: Why Pentose-And Not Hexose-Nucleic Acids? Part III. Oligo(2′,3′-dideoxy-β-D-glucopyranosyl)nucleotides. (‘Homo-DNA’): Base-Pairing Properties1 The paper presents results of a comprehensive investigation on the pairing properties of homo-DNA oligonucleotides, the preparation of which has been described in Part II of this series [2]. The investigation was carried out by using established methods described in the literature for the characterization of oligonucleotides in the natural series, such as determination of melting temperatures of oligonucleotide duplexes by temperature-dependent of melting temperatures, determination of pairing stoichiometry by ratio-dependent UV spectroscopy of binary mixtures of pairing partners, temperature-dependent CD spectroscopy, gel electrophoresis under non-denaturing conditions, and – in selected cases – 1H – and31P-NMR spectroscopy. The systematic comparison of the paring properties of homo-DNA oligonucleotides with corresponding DNA nucleotides (up to dodecamers) indicates that homo-DNA is a highly efficient, autonomous, artificial pairing system with a pairing behavior that is in part similar to, but also, in part, strikingly different from, the pairing behavior of DNA. The pairing properties established so far are listed below in a manner that reflects the sequence of subtitles in Chapt.2 of the text; they were determined under the conditions: H2O, 0.15M NaCl, 0.01M Tris-HCl buffer, pH 7, oligonucleotide concentrations in the μM range, 1:1 ratio of single strands in the case of non-selfcompementary sequences.

Physicochemical and Structural Properties of Non-Steroidal Anti-inflammatory Oxicams

Abstract: Using the five therapeutic oxicams 1-5, we showed that isosteric replacements result in remarkable changes in the physicochemical and structural properties of congeners. Thus. the acidity of the phenolic OH group is relatively higher in the oxicams containing a pyridinyl moiety, i.e. in piroxicam (1), tenoxicam (2), and lornoxicam (3), due to their zwitterionic nature- This consequently influences their lipophilicity profile at different ionization states. Furthermore, partitioning behaviour in octan-1-ol/H2O and heptane/H2O systems suggests an internal H-bond between the enolic OH and the amide C=O group. The anionic oxicams readily partition into the octanol phase at pH 7.4 and not at all into the heptane phase. Only the partition coefficients of oxicams measured in the heptane/H2O system, but not in the octanol/H2O system, correlate with their transfer across the blood-brain barrier- This implies that only the neutral form of oxicams crosses the blood-brain barrier

Modification of Cyclosporin A (CS): Generation of an enolate at the sarcosine residue and reactions with electrophiles

Abstract: Strong bases (lithium diisopropylamide (LDA) or BuLi) convert cyclosporin A (CS) to hexalithio derivative containing a Li alkoxide, four Li azaenolate, and one Li enolate units. The Li6 compound is solubilized in tetrahydrofuran (THF) by addition of excess LDA or LiCl. Reactions with electrophiles (alkyl halides, aldehydes, ClCO2R, CO2, (RS)2, D2O) at low temperatures give products containing new side chains in amino-acid residue 3 of the cyclic undecapeptide (see 1–13, Schemes 1, and 2, and Figs. 1 and 2) in moderate to high yields and, with Re- or Si-selectivities, depending upon the conditions of lithiation of up to 7:1, Pure CS derivatives (Scheme 2, Table 1 in the Exper. Part) can be isolated by column chromatography. N-Alkylations or cleavage of the peptide backbone by carbonyl addition occur only at higher temperatures and/or with prolonged reaction times (see 14 and 15 in Scheme 4). Very little or no epimerization of stereogenic centers occurs under the conditions employed. Possible reasons for the feasibility of these surprizing conversions of CS are discussed (Schemes 4 and 5 and Fig. 3). For comparision, [MeAla3]CS (2b) and [D-MeAla3]CS (2a) were also prepared by conventional peptide synthesis in solution (Schemes 6 and 7). Their 1H- and 13C-NMR spectra are compared with those of CS (Table 2 in the Exper. Part).

Magnetic‐Field‐Dependent Electronic Relaxation of Gd3+ in Aqueous Solutions of the Complexes [Gd(H2O)8]3+, [Gd(propane‐1,3‐diamine‐N,N,N′,N′‐tetraacetate)(H2O)2]−, and [Gd(N,N′‐bis[(N‐methylcarbamoyl)methyl]‐3‐azapentane‐1,5‐diamine‐3,N,N′‐triacetate)(H2O)] of interest in magnetic‐resonance imaging

Abstract: EPR Spectra have been measured for aqueous solutions of a series of Gd3+ complexes at variable temperature and a range of magnetic fields; S-band (0.14 T), X-band (0.34 T), Q-band (1.2 T), and 2-mm-band (5.0 T). The major contribution to the observed line widths is magnetic-field-dependent and is interpreted as being due to the modulation of the zero-field splitting produced by distortion of the complexes from perfect symmetry. The transverse and longitudinal relaxation matrices for an 8S ion with such an interaction have been calculated using Redfield theory with vector-coupling methods, and diagonalised numerically to obtain relaxation rates and intensities for the degenerate transitions which contribute to the multiplet. The observed line width, which is inversely proportional to the magnetic field at low temperatures, is best described by the intensity-weighted mean transverse relaxation time for the four transitions with non-zero intensity. A least-squares fit of the data yields the square of the zero-field splitting tensor, Δ2, and a correlation time, τv, with activation energy, Ev. The physical significance of these parameters and the extent of validity of the theoretical approach are considered. The parameters are used to predict the magnetic-field dependence of the longitudinal and transverse electronic relaxation times, which are discussed in the context of their relevance to 1H-NMR relaxivity.

A New Helicopodand: Molecular Recognition of Dicarboxylic Acids with High Diastereoselectivity

Abstract: The helicopodand (PM)-2 is prepared following the photocyclodehydrogenation route to helicenes (Scheme). At the ends of a [7]helicene backbone, this acyclic receptor (‘podand’) possesses a H-bonding recognition site shaped by two convergent N-(pyridin-2-yl)carboxamide (CONH(py)) units. In the crystal of diethyl [7]helicene-2,17-dicarboxylate ((PM)-3), a direct synthetic precursor of 2, molecules of the same chirality form stacks, and two stacks of opposite chirality are interlocked in a pair having average face-to-face aromatic contacts of 3.82 A between benzene rings of different enantiomers (Fig. 2). In contrast, two conformations are observed in the crystal structure of 2, one with both CONH(py) residues pointing with their H-bonding centers NH/N away from the binding site (‘out-out’) and a second (‘in-out’) with one of the two CONH(py) residues pointing towards the binding site (‘in’; Fig. 4). While no H-bonding network propagates throughout the crystal, enantiomers of 2 in the different conformations ‘out-out’ and ‘in-out’ form H-bonded pairs that are further stabilized by a H-bond to one molecule of CHCl3. In the productive ‘in-in’ conformation, 2 forms stable 1:1 complexes with α,ω-dicarboxylic acids in CHCl3, and a diastereoselectivity in complexation of Δ(ΔG°) = 1.4 kcal mol−1 is measured for two substrates differing only in the (E)/(Z)-configuration at their double bond (see Table 2). A comprehensive force-field molecular-modeling study suggests that only the (E)-derivative possesses the correct geometry for a ditopic four-fold H-bonding interaction between its two COOH residues and the two CONH(py) groups in 2 (Fig. 5). With N,N′-bis [(benzyloxy)carbonyl]-L-cystine, the formation of diastereoisomeric complexes with (PM)-2 is observed (Fig. 7).

Catalytic Enantioselective Hydrosilylation of Aromatic Ketones Using Rhodium Complexes of TADDOL-Derived Cyclic Phosphonites and Phosphites

Abstract: Cyclic phosphonites and phosphites 2–4 are readily available from Cl2PR and (R,R)- or (S,S)-α,α,α′,α′-tetraaryl-1,3-dioxolane-4,5-dimethanols (= TADDOLs 1, which, in turn, are only two steps away from tartrate); the X-ray crystal structure of one representative, the phenyl phosphonite 2b, was determined. Five previously described and six new ones of the chiral P derivatives were tested as ligands for RhI- and PdO-catalyzed reactions such as hydrocarbonylations, hydroborations, and hydrosilylations of CC bonds; while the resulting catalysts were highly active and regioselective, they did not lead to useful enantiomer enrichment in the products (Scheme 1). In contrast, hydrosilylation of phenyl and 2-naphthyl methyl or ethyl ketone by Ph2SiH2 (1.2 equiv.) gave, after desilylation, the corresponding secondary alcohols of (R)-configuration with up to 87% ee in the presence of 0.1 equiv. of the penta(2-naphthyl)-substituted phosphonite 3d and 0.02 mol-equiv. of Rh (Table 1).

Enantioselective Copper‐Catalyzed 1,4‐Addition of Grignard Reagents to α,β‐Unsaturated Carbonyl Compounds

Abstract: The enantioselective copper-catalyzed 1,4-addition of Grignard reagents to α,β-unsaturated carbonyl compounds was studied with the following CuI compounds as catalyst precursor and 1,2:5,6-di-O-isopropylidene-3-thio-α-D-glucofuranose (Hsiig) as chiral ligand: CuI, iodo[bis(dibutylsulfide)]copper(I), [Cu(siig)], [Cu(siig)(pp)] (pp =1,2-bis)(diphenylphosphinoethene), and tetrakis[iodo(tributylphosphine)]copper(I). The addition of BuMg halides to cyclohex-2-en-1-one was tested under several reaction conditions. The chemical yields and regioselectivities for this reaction were, in all cases, larger than 90 and 98%, respectively, and independent of the experimental conditions. The enantioselectivity was strongly dependent on the reaction conditions and reached a maximum of 60%. Several other substrates were also tested in the above reaction. The X-ray crystal structure for [Cu(siig)(pp)] was determined by X-ray crystallography.

Synthesis, Structure, and Antimalarial Activity of Tricyclic 1,2,4-Trioxanes Related to Artemisinin

Abstract: Two sets of tricyclic 1,2,4-trioxanes containing the ABC (10, 11) and ACD ring portions (21, 22, 32, 33, 37, and 38) of artemisinin (1) were synthesized by successive photo-oxygenation of appropriate enol-ether precursors to 1,2-dioxanes and inter- and intramolecular reaction with a carbonyl compound or oxo-substituted side-chain. The structures of 10, 21, and 22 were determined by X-ray analysis. The anti-malarial activity of all trioxanes, except 37 and 38, was evaluated in vitro against chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum parasites. Trioxanes 11 and 21 were as active as artemisinin (1). It was found that neither the lactone function nor rings B and D of 1 were essential for activity. A possible pharmacophore for artemisinin-like activity, which embodies a spirocyclopentane group attached to C(3) of 1,2,4-trioxane, was proposed.

Asymmetric catalysis by vitamin B12 : the isomerization of achiral aziridines to optically active allylic amines

Abstract: Achiral N-acylaziridines are isomerized to optically active N-acyl-allylamines in ee's of up to 95% by catalytic amounts of cob(I)alamin in MeOH.

Sterically Congested Phosphite Ligands: Synthesis, crystallographic characterization, and observation of unprecedented eight-Bond 31P,31P coupling in the 31P-NMR spectra

Abstract: The synthesis and characterization of 2-{1-{3,5-bis(1,1-dimethylethyl)-2-{[2,4,8,10-tetrakis(1,1-dimethylethyl)dibenzo[d,f][1,3,2]dioxaphosphepin-6-yl]oxy}phenyl}ethyl}-4,6-bis(1,1-dimethylethyl)phenyl diphenyl phosphite (6) is described. In the 31P-NMR spectrum (1H-decoupled) of 6, an unprecedented eight-bond P,P coupling of J = 72.8 Hz is observed. In the X-ray crystal structure of 6, an intramolecular P–P distance of 3.67 A is found, which is within the sum of the van-der-Waals radii of the P-atoms. The observed intramolecular P–P distance suggests that a through-space coupling mechanism is operative. The solid-state conformation of 6 is compared to the conformation obtained by semi-empirical MO geometry optimizations (PM3 method). The calculated geometry suggests that the solid-state structure is near a true energy minimum, but that crystal-packing forces decrease the intramolecular P–P distance in the solid state. In the absence of crystal-packing forces, however, the collisional and vibrational energy available in solution may lead to the population of states with a shortened intramolecular P–P distance in 6. The proximity of the P-atoms in 6 is due to restricted conformational freedom resulting from steric congestion within the molecule. The free energy of activation (ΔG* = 10.2 and 10.8 kcal/mol for unequal populations of exchanging conformers) for ring inversion of the dibenzo[d,f][1,3,2]dioxaphosphepin ring in 6 is determined by variable-temperature 31P-NMR spectroscopy. Semi-empirical MO calculation on model compounds suggest that the structure of the transition state for ring inversion has the two aryl rings and O-atoms in a common plane, with the P-atom lying above this plane.

Über Diels-Alder-Reaktionen des C60-Fullerens Vorläufige Mitteilung

Abstract: On Diels-Alder Reactions of the C60-Fullerene We report on the regioselective [4+2] cycloaddition of Buckminsterfullerene C60(1) at room temperature with 2,3-dimethylbuta-1,3-diene and with the monoterpene 7-methyl-3-methylideneocta-1,6-diene (= myrcene) and on the spectroscopic characterization of the corresponding crystalling monoadducts 2 and 3. According to these experiments, 1 acts as a reactive dienophile, which can be functionalized regioselectively under mild and controlled conditons.

Breakdown of Chlorophyll: A Tetrapyrrolic Chlorophyll Catabolite from Senescent Rape Leaves. Preliminary communication†

Abstract: The experiments leading to the isolation and to the elucidation of the constitution of Bn-NCC-1, a colourless non-fluorescent chlorophyll catabolite from senescent cotyledons of rape (Brassica napus L.), are described. A series of fast-atom-bombardment (FAB) mass and 1H- and 13C-NMR spectral experiments are used to determine the constitution of the catabolite Bn-NCC-1. The structural information available indicates Bn-NCC-1 to be a 1-formyl-19-oxobilane, structurally related to ‘RP 14’, isolated earlier from artificially aged primary leaves of barley. The major differences between the constitution of the metal-free chlorophyll pheophorbide a and that of Bn-NCC-1 concern oxygenolytic opening of the porphinoid macrocycle at C(4)C(5), saturation at the other meso positions, hydrolysis of the methyl-ester function, and functionalization by a malonic-acid unit of the side chain at C(8). This work provides for the first time the structural data of a chlorophyll-degradation product from senescent plant leaves formed under normal growth conditions.

Transition Metal-Diene Complexes in Organic Synthesis. Part 15. Iron-mediated total synthesis of carbazomycin A and B

Abstract: We developed a very efficient methodology for the synthesis of the antibiotics carbazomycin A (1) and B (2) by oxidative coupling of cyclohexa-1,3-diene and the corresponding arylamine 10 (Scheme 5 and Schemes 7 and 9, resp.). The overall process is achieved by a consecutive Fe-induced formation of the CC and the CN bond. The major benefit of our Fe-mediated carbazole synthesis is that the coupling process is possible with fully functionalized arylamines 10. Therefore, highly convergent syntheses of carbazole alkaloids are feasible, and linear multistep sequences as required by using classical procedures are avoided. The total synthesis of 1 and 2 emphasizes this characteristic feature of the Fe-mediated construction of the carbazole framework.

Cyclische Oligomere von (R)-3-Hydroxybuttersäure: Herstellung und strukturelle Aspekte†

Abstract: Cyclic Oligomers of (R)-3-Hydroxybutanoic Acid: Preparation and Structural Aspects The oligolides containing three to ten (R)-3-hydroxybutanoate (3-HB) units (12-through 40-membered rings 1–8) are prepared from the hydroxy acid itself, its methyl ester, its lactone (‘monolide’), or its polymer (poly(3-HB), mol. wt. ca. 106 Dalton) under three sets of conditions: (i) treatment of 3-HB (10) with 2,6-dichlorobenzoyl chloride/pyridine and macrolactonization under high dilution in toluene with 4-(dimethylamino)pyridine (Fig. 3); (ii) heating a solution (benzene, xylene) of the β-lactone 12 or of the methyl ester 13 from 3-HB with the tetraoxadistanna compound 11 as trans-esterification catalyst (Fig. 4); (iii) heating a mixture of poly(3-HB) and toluene-sulfonic acid in toluene/1,2-dichloroethane for prolonged periods of time at ca. 100° (Fig. 6). In all three cases, mixtures of oligolides are formed with the triolide 1 being the prevailing component (up to 50% yield) at higher temperatures and with longer reaction times (thermodynamic control, Figs. 3–6). Starting from rac-β-lactone rac-12, a separable 3:1 to 3:2 mixture of the l,u- and the l,l-triolide diasteroisomers rac-14 and rac-1, respectively, is obtained. An alternative method for the synthesis of the octolide 6 is also described: starting from the appropriate esters 15 and 17 and the benzyl ether 16 of 3-HB, linear dimer, tetramer, and octamer derivatives 18–23 are prepared, and the octamer 23 with free OH and CO2H group is cyclized (6) under typical macrolactonization conditions (see Scheme). This ‘exponential fragment coupling protocol’ can be used to make higher linear oligomers as well. The oligolides 1–8 are isolated in pure form by vacuum distillation, chromatography, and crystallization, an important analytical tool for determining the composition of mixtures being 13C-NMR spectroscopy (each oligolide has a unique and characteristic chemical shift of the carbonyl C-atom, with the triolide 1 at lowest, the decolide 8 at highest field). The previously published X-ray crystal structures of triolide 1, pentolide 3, and hexolide 4 (two forms), as well as those of the l,u-triolide rac-14, of tetrolide ent-2, of heptolide 5, and of two modifications of octolide 6 described herein for the first time are compared with each other (Figs. 7–10 and 12–15, Tables 2 and 5–7) and with recently modelled structures (Tables 3 and 4, Fig. 11). The preferred dihedral angles τ1 to τ4 found along the backbone of the nine oligolide structures (the hexamer and the larger ones all have folded rings!) are mapped and statistically evaluated (Fig. 16, Tables 5–7). Due to the occurrence of two conformational minima of the dihedral angle OCOCH2CH (τ3 = + 151 or −43°), it is possible to locate two types of building blocks for helices in the structures at hand: a right-handed 31 and a left-handed 21 helix; both have a ca. 6 A pitch, but very different shapes and dispositions of the carbonyl groups (Fig. 17). The 21 helix thus constructed from the oligolide single-crystal data is essentially superimposable with the helix derived for the crystalline domains of poly(3-HB) from stretched-fiber X-ray diffraction studies. The absence of the unfavorable (E)-type arrangements around the OCOR bond (‘cis-ester’) from all the structures of (3-HB) oligomers known so far suggests that the model proposed for a poly(3-HB)-containing ion channel (Fig. 2) must be modified.

Luminescence of Europium(III) Chelates with 4‐(Arylethynyl)pyridines as Ligands

Abstract: Some Spectral properties and luminescence intensities of EuIII chelates with 4-(arylethynyl)pyridine-2,6-dicarboxylic acids 1–15 and 2,2′,2″,2′″-{[4-(arylethynyl)pyrridine-2,6-diyl]bis(methylenenitrilo)} tetrakis(acetic acids) 16–26 were measured both in H2O and EtOH solutions for the purpose of developing suitable labels to be used in time-resolved luminescence-based bioaffinity assays (Tables 1 and 2). The substitution at the Ar group has a significant effect upon the observed luminescence intensities, excitation wavelengths, and decay constants of the complexes, Moreover, the changes in the environment cause great variation in those properties of certain EuIII chelates.

Application of electrospray mass spectrometry for characterizing supramolecular coordination complexes

Abstract: The Electrospray Mass Spectrometry (ES-MS) of eight different supramolecular complexes shows that the molecular peaks of the desolvated multiply charged cations can be recorded more easily than by Fast-Atom-Bom-bardment Mass Spectrometry (FAB-MS) measurements of similar compound. The preliminary application of the ES-MS technique to self-assembled helical complexes obtained from ligands L3 to L8 with various metal ions (Cu, Co, Eu, Tb) indicates that ES mass spectra qualitatively reflect the species present MeCN solution.

Warum Pentose‐ und nicht Hexose‐Nucleinsäuren??. Teil VI. ‘Homo‐DNS’: 1H‐, 13C‐, 31P‐ und 15N‐NMR‐spektroskopische Untersuchung von ddGlc(A‐A‐A‐A‐A‐T‐T‐T‐T‐T) in wässriger Lösung

Abstract: Why Pentose- and Not Hexose-Nucleid Acids? Part IV. ‘Homo-DNA’: 1H-, 13C-, 31P-, and 15N-NMR-Spectroscopic Investigation of ddGlc(A-A-A-A-A-T-T-T-T-T) in Aqueous Solution From a comprehensive NMR structure analysis, it is concluded that the ‘homo-DNA’ oligonucleotide ddGlc(A-A-A-A-A-T-T-T-T-T) in 3 mM D2O solution (100 mM NaCl, 50 mM phosphate buffer, pH 7.0, T = 50°) forms a duplex of C2-symmetry, with its self-complementary oligonucleotide strands in antiparallel orientation. The 2′,3′-dideoxy-β-D-glucopyranosyl rings are in their most stable chair conformation, with all three substituents equatorial and with the adenine as well as the thymine bases in the anti-conformation. The base pairing is of the Watson-Crick type; this pairing mode (as opposed to the reverse-Hoogsteen mode) was deduced from the observation of inter strand NOEs between the adenine protons HC(2) and the pyranose protons Hα–C(2′) of the sequentially succeeding thymidine nucleotides of the opposite strand, a correlation which discriminates between the Watson-Crick and the reverse-Hoogsteen pairing mode. The NOEs of the NH protons with either the adenine protons HC(2) or HC(8), that are normally used to identify the pairing mode in DNA duplexes, cannot be observed here, because the NH signals are very broad. This line broadening is primarily due to the fact that the exchange of the imino protons with the solvent is faster than for corresponding DNA duplexes. Computer-assisted modeling of the [ddGlc(A5-T5)]2 duplex with the program CONFOR [23], using the linear (idealized) homo-DNA single-strand conformation (α = −60°, β = 180°, γ = 60°, δ = 60°, ϵ = 180°, ζ = −60°, see [1] [3]) as the starting structure, resulted in two duplex models A and B (see Figs. 27–32, Scheme 9, and Table 4) which both contain quasi-linear double strands with the base-pairing axis inclined relative to the strand axes by ca. 60° and 45°, respectively, and with base-pair stacking distances of ca. 4.5 A. While neither of the two models, taken separately, can satisfy all of the NMR constraints, the NMR data can be rationalized by the assumption that the observed duplex structure represents a dynamic equilibrium among conformers which relate to models A and B as their limiting structure. The required rapid equilibrium appears feasible, since the models A and B are interconvertible by two complementary 120° counter rotations around the α-axis and the γ-axis, respectively, of the phosphodiester backbone. The models A and B correspond to the two types of linear (idealized) single-strand backbone conformation derived previously by qualitative conformational analysis without and with allowance for gauche-trans-phosphodiester conformations, respectively [1] [3]. Refinement of the models A and B with the use of the program AMBER [27] by energy minimization in a water bath and molecular-dynamics simulations (2 ps, 300° K) resulted in two dynamic structures (Figs. 33 and 34, Table 4). These have roughly the same energy, closely resemble the starting structures A and B, and satisfy - as an ensemble - all of the NMR constraints without violating any van der Waals distances by more than 0.2 A. Extensive fluctuations in base-pair distance and deviations from base-pair coplanarity, as well as the presence of water molecules in the cavities between some of the base pairs, were observed in both dynamic structures A and B, which, on the other hand, did not mutually interconvert within the short simulation time period used. These model properties, together with the conjectured equilibrium between the two structure types A and B, lead to the hypothesis of a homo-DNA duplex containing a ‘partially molten’ pairing core. This proposal could qualitatively account for a high rate of the NH exchange, as well as for part of the previously established [3] deficits in both enthalpic stabilization and entropic destabilization of homo-DNA duplexes relative to corresponding DNA duplexes. The phenomenon of the higher overall stability of homo-DNA duplexes vs. DNA duplexes (e.g, [ddGlc(A5-T5)]2, Tm = 59° vs. [d(A5-T5)]2, Tm = 33°, both at c ≈ 50 μM [3]) can then be seen as the result not only of a higher degree of conformational preorganization of the homo-DNA single strand toward the conformation of the duplex backbone [1] [3], but also of the entropic benefit of greater disorder in the central pairing zone of the homo-DNA duplex. This view of the structure of a homo-DNA duplex relates its characteristic properties to a central structural feature: the average base-pair distance in the models of homo-DNA is too large for regular base stacking (ca. 4.5 A vs. ca. 3.5 A in DNA). This difference in the distances between adjacent base pairs is a direct consequence of the quasi-linearity of the homo-DNA double strand as opposed to the right-handed twist of the helical DNA duplexes [1] [3], which is directly related to the specific conformational properties of pyranose rings as opposed to furanose rings [1]. Thus, the structural hypothesis derived from the NMR analysis of [ddGlc(A5-T5)]2 relates the conformational differences between homo-DNA and DNA directly to the sugar ring size, which is the essential constitutional difference between the two types of structure. The English footnotes to Figs. 1–34, Schemes 1–9, and Tables 1–4 provide an extension of this summary.

Influence of chelating groups on the luminescence properties of europium(III) and terbium(III) chelates in the 2,2'-bipyridine series

Abstract: Eight different 2,2′-bipyridine derivatives, i.e. 2, 5, 8, 10, 12, 13, 15, and 19 (Schemes 1 and 2), were prepared to study the influence of the chelating groups on the luminescence properties of their EuIII and TbIII chelates. According to our luminescence results, 2,2′-(methylenenitrilo)bis(acetic acid) as well as (methylenenitrilo)bis-(methylphosphonic acid) in 6- and 6′-position of 2,2′-bipyridine is a suitable group when developing luminescent markers for bioaffinity assays based on time-resolved luminescence measurement.

Homogeneous Catalysis with Dicationic PdII Complexes: Aldol reaction of methyl isocyanoacetate with benzaldehyde

Abstract: A series of dicationic PdII-acetonitrile complexes containing bi- and tridentate nitrogen and bidentate phosphine ligands (some of which are chiral) has been prepared as their BF4 salts. The molecular structures for two of these, [Pd(CH3CN)2(bipy)] (BF4)2 (4) and [Pd(CH3CN)((pybox)(i-Pr))] (BF4)2((S,S)-pybox(i-Pr) = 2,6-bis[(S)-4′-isopropyloxazolin-2′-yl]pyridine, 5) have been determined by X-ray diffraction. All of these complexes are shown to be effective homogeneous catalysts for the aldol-type condensation of the isonitrile, methyl isocyanoacetate, with benzaldehyde. Two isonitrile complexes, [Pd(2,2′-bipyridyl)(CNCH2COOCH3)2] (BF4)2 and [Pd((S,S)-pybox(i-Pr))(CNCH2COOCH3)] (BF4)2, have also been prepared.

Tetrakis[(4S)‐4‐phenyloxazolidin‐2‐one]dirhodium(II) and Its Catalytic Applications for Metal Carbene Transformations

Abstract: The synthesis and X-ray structure of the binuclear complex tetrakis[(4S)-4-phenyloxazolidin-2-one]-dirhodium(II) ([Rh2{(4S)-phox}4]) are reported. Structure-selectivity comparisons are made for typical metal carbene transformations, such as inter- and intramolecular cyclopropane formation, intermolecular cyclopropene formation and intramolecular C–H insertions of diazoacetates and diazoacetamides. The enantioselectivity achieved in the [Rh2{(4S)-phox}4]-catalyzed reactions is intermediate between that of [Rh2{(5S)-mepy}4] and [Rh2{(4R)-bnox}4], which were described previously (mepy = methyl 5-oxopyrrolidine-2-carboxylate; bnox = 4-benzyloxazolidin-2-one). In contrast to other catalyzed intermolecular cyclopropane formations, those using [Rh2{(4S)-phox}4] result preferentially in formation of the cis-cyclopropane.

C‐Alkylation of Sarcosine Residues in Cyclic Tetrapeptides via Lithium Enlates

Abstract: The cyclic tetrapeptides cyclo(-Leu-Sar-Gly-), cyclo(-Val-Sar-Sar-Gly-), and cylco(-Meleu-Gly-D-Alasar-) have been synthesized from the component amino acids (BOP-Cl coupling), using the pentafluorophenyl esters for the cyclization step (42, 13, and 30% yield, respectively). Multiple deprotonation (LDA in THF/LiBr/DMPU) and addition of highly reactive electrophiles (CF3CO2D, MeI, CH2O, CH2CHCH2Br, PhCH2Br) produce cyclic tetrapeptides with additional substituents introduced diastereoselectively (70 to > 98% ds) in yields ranging from 20 to 90%. The C-alkylatd products are all derived from a sarcosine-enolate moiety adjacent to another N-methylamino acid. The structures of the resulting products are determined by NMR spectroscopy (DNOE and ROESY techniques) and by hydrolysis to the parent amino acids, suitable derivatization, and analysis by chromatography on a chiral GC column. It was shown in two cases that the overall yield of cyclization/alkylation to give a disubstitued cyclic tetrapeptide is higher than that of a synthesis of the same product from the corresponding amino-acid building blocks. Surprising temperature and salt effects on the yields and selectivities of the reactions of the cyclic tetrapeptide enolates are presented, and possible mechanistic interpretations are discussed.

Metabolic Products of Microorganisms. Part 265. Prelactones C and B, oligoketides from Streptomyces producing concanamycins and bafilomycins

Abstract: Prelactones C (3) B (8) were isolated from the concanamycin-producing Streptomyces sp. (strain Go 22/15) and bafilomycin-producing Streptomyces griseus (strain Tu 2599), respectively, by chemical screening methods. The constitution and relative configuration of 3 and 8 were established by one- and two-dimensional NMR methods. The absolute configuration of 3 was determined using the Helmchen method and that of 8 by CD spectra. The structural properties and absolute configuration of these new δ-lactones reveal strong similarities to the hemiacetal portion of the corresponding macrolide antibiotics. Their possible role in the early polyketide formation of unusual macrolactones is discussed.

Muricatetrocins A and B and Gigantetrocin B: Three New Cytotoxic Monotetrahydrofuran-Ring Acetogenins from Annona muricata

Abstract: Extracts from the seeds of Annona muricata yielded three new Annonaceous acetogenins: muricatetrocin A (= (5S)-3-{(2R)-2-hydroxy-9-{(2R,5S)-tetrahydro-5-[(1S,4S,5S)-1,4,5-trihydroxyheptadecyl]furan-2-yl}nonyl}-5-methylfuran-2(5H)-one; 1), muricatetrocin B (= (5S)-{(2R)-2-hydroxy-9-{(2S,5S)-tetrahydro-5-[(1S,4S,5S)-1,4,5-trihydroxyheptadecyl]furan-2-yl}nonyl}-5-methylfuran-2(5H)-one; 2), and gigantetrocin B (= (5S)-3-{(2R)-2-hydroxy-7-{(2S,5S)-tetrahydro-5-[(1S,4R,5R)-1,4,5-trihydroxynonadecyl]furan-2-yl}heptyl}-5-methyl-furan-2(5H)-one; 3). Their C-skeletons were deduced by mass spectrometry. Configurations were determined by 1H-NMR of ketal derivatives and 2D-NMR experiments utilizing Mosher esters. A previously described compound, gigantetrocin A (= (5S)-3-{(2R)-2-hydroxy-7-{(2S,5S)-tetrahydro-5-[(1S,4S,5S)-1,4,5-trihydroxynonadecyl]furan-2-yl}heptyl}-5-methylfuran-2-(5H)one; 4), was also isolated and is new to this species. Compounds 1–4 were all selectively cytotoxic for the HT-29 human colon-tumor cell line with potencies at least 10 times that of adriamycin.

D-gluconhydroximo-1,5-lactam and related N-arylcarbamates : theoretical calculations, structure, synthesis, and inhibitory effect on β-glucosidases

Abstract: The known D-gluconhydroximo-1,5-lactam (= D-glucono-1,5-lactam oxime) 7a, its nitrogen isotopomers 7b and 7c, and the N-arylcarbamates 26–29 were synthesized from 2,3,4,6-tetra-O-benzyl-D-glucono-1,5-lactam (11a) and its nitrogen isotopomer 11b to establish the controversial structure of 7a and to study the inhibition of β-glucosidases by the N-arylcarbamates 26–29. Conversion of 11a with Lawesson's reagent yielded a mixture of the thionolactam 15a and its manno-configurated isomer 16a, which was transformed into a mixture of the benzylated hydroximo-lactam 13a and the manno-isomer 17a. Debenzylation (Na/NH3) and acetylation of this mixture led to the gluco-configurated pentaacetate 14a and the manno-isomer 18a. Treatment of 11a with Et3O·BF4 and then with H2NOH gave exclusively the benzylated D-gluconhydroximo-1,5-lactam (benzylated D-nojirilactam oxime) 13a, which was transformed into 14a. Deacetylation of 14a yielded the hydroximo-lactam 7a. The isotopomers 7b and 7c were obtained by analogous reaction sequences, using either 15NH3 or 15NH2OHHCl. To prepare the acetylated N-arylcarbamates 20–25, 13a was debenzylated and acetylated (→ 14a), followed by selective deacetylation to the tetraacetate 19a and treatment with the appropriate isocyanates. The structure of the 2-chlorophenyl carbamate 21 was established by X-ray analysis. Deacetylation of 20–23 led to the N-arylcarbamates 26–29. The 15N-NMR spectra of 7b, 7c, and of their precursors 13b, 13c, 14b, and 14c, show that the CN bond in all these lactam oximes is exocyclic as predicted from semiempirical and ab initio SCF-MO calculations on the structure of acetamide oxime and 5-pentanelactam oxime. According to these calculations, 5-pentanelactam oxime is a (Z)-configurated, flattened chair. X-ray analysis established the structure of D-glucono-1,5-lactam oxime (7a) in the solid state, where it adopts a conformation between 4C1 and 4H3. In H2O, 7a is a flattened 4C1. The calculations also predict that protonation at the exocyclic N-atom strengthens the conjugation between the endocyclic N-atom and the hydroxyimino group, and leads to a half-chair conformation. This is evidenced by the chemical shift differences in the 15N-NMR spectra observed upon protonation of 7b and 7c. The hydroximolactam 7a and the N-arylcarbamates 26–29 are competitive inhibitors of the β-glucosidases from sweet almond (emulsin) and from Agrobacterium faecalis (= Abg), with KI values between 8 and 21·10−6M against emulsin (at pH 6.8) and between 0.15 and 1.2·10−6M against Abg (at pH 7.0).