Showing papers in "Helvetica Chimica Acta in 1996"
TL;DR: The β-hexapeptide (H-β-HVal-β -HAla-Leu)2-2-OH (2) was obtained from the component Lβ-amino acids by conventional peptide synthesis, including fragment coupling as discussed by the authors.
Abstract: The β-hexapeptide (H-β-HVal-β-HAla-β-HLeu)2-OH (2) was prepared from the component L-β-amino acids by conventional peptide synthesis, including fragment coupling. A cyclo-β-tri- and a cyclo-β-hexapeptide were also prepared. The β-amino acids were obtained from α-amino acids by Arndt-Eistert homologation. All reactions leading to the β-peptides occur smoothly and in high yields. The β-peptides were characterized by their CD and NMR spectra (COSY, ROESY, TOCSY, and NOE-restricted modelling), and by an X-ray crystal-structure analysis. β-Sheet-type structures (in the solid state) and a compact, left-handed or (M) 31 helix of 5-A pitch (in solution) were discovered. Comparison with the analogous secondary structures of α-peptides shows fundamental differences, the most surprising one at this point being the greater stability of β-peptide helices. There are structural relationships of β-peptides with oligomers of β-hydroxyalkanoic acids, and dissimilarities between the two classes of compounds are a demonstration of the power of H-bonding. The β-hexapeptide 2 is stable to cleavage by pepsin at pH 2 in H2O for at least 60 h at 37°, while the corresponding α-peptide H-(Val-Ala-Leu)2-OH is cleaved instantaneously under these conditions. The implication of the described results are discussed.
642 citations
TL;DR: The results fully confirm predicted structural effects: incorporation of a single ‘wrong’ residue in the central position of the β-heptapeptide derivatives A fully confirms the helical structure of such β-peptides (previously discovered in pyridine solution).
Abstract: Structural prerequisites for the stability of the 31 helix of β-peptides can be defined from inspection of models (Figs. 1 and 2): lateral non-H-substituents in 2- and 3-position on the 3-amino-acid residues of the helix are allowed, axial ones are forbidden. To be able to test this prediction, we synthesized a series of heptapeptide derivatives Boc-(β-HVal-β-HAla-β-HLeu-Xaa-β-HVal-β-HAla-β-HLeu)-OMe 13–22 (Xaa = α- or β-amino-acid residue) and a β-depsipeptide 25 with a central (S)-3-hydroxybutanoic-acid residue (Xaa = –OCH(Me)CH2C(O)–) (Schemes 1 3). Detailed NMR analysis (DQF-COSY, HSQC, HMBC, ROESY, and TOCSY experiments) in methanol solution of the β-hexapeptide H(-β-HVal-β-HAla-β-HLeu)2-OH (1) and of the β-heptapeptide H-β-HVal-β-HAla-β-HLeu-(S,S)-β-HAla(αMe)-β-HVal-β-HAla- β-HLeu-OH (22), with a central (2S,3S)-3-amino-2-methylbutanoic-acid residue, confirm the helical structure of such β-peptides (previously discovered in pyridine solution) (Fig.3 and Tables 1–5). The CD spectra of helical β-peptides, the residues of which were prepared by (retentive) Arndt-Eistert homologation of the (S)- or L-α-amino acids, show a trough at 215 nm. Thus, this characteristic pattern of the CD spectra was taken as an indicator for the presence of a helix in methanol solutions of compounds 13–22 and 25 (including partially and fully deprotected forms) (Figs.4–6). The results fully confirm predicted structural effects: incorporation of a single ‘wrong’ residue ((R)-β-HAla, β-HAib, (R,S)-β-HAla(α Me), or N-Me-β-HAla) in the central position of the β-heptapeptide derivatives A (see 17, 18, 20, or 21, resp.) causes the CD minimum to disappear. Also, the β-heptadepsipetide 25 (missing H-bond) and the β-heptapeptide analogs with a single α-amino-acid moiety in the middle (13 and 14) are not helical, according to this analysis. An interesting case is the heptapeptide 15 with the central achiral, unsubstituted 3-aminopropanoic-acid moiety: helical conformation appears to depend upon the presence or absence of terminal protection and upon the solvent (MeOH vs. MeOH/H2O).
294 citations
TL;DR: The first asymmetric intramolecular Stetter reaction using the chiral triazolium salt as catalyst was reported in this paper, starting from the easily accessible 4-(2-formylphenoxy)but-2-enoates 2.
Abstract: The first asymmetric intramolecular Stetter reaction is reported, using the chiral triazolium salt 1 as catalyst. Starting from the easily accessible 4-(2-formylphenoxy)but-2-enoates 2, this protocol opens up an enantioselective pathway to the benzo-annulated pyran-4-ones (chroman-4-ones) 3a–h with good yields and enantiomeric excesses of up to 74%.
235 citations
TL;DR: In this paper, the TADDOL moieties were copolymerized with styrene and divinylbenzene in a suspension, yielding polymers as beads with a rather uniform particle-size distribution (150-45 μm).
Abstract: α,α,α′,α′-Tetraaryl-1,3-dioxolane-4,5-dimethanols (TADDOLs), containing styryl groups either at C(2) of the heterocyclic ring or in the α-position, were prepared in the usual way (18–22, 24, 25). These compounds were copolymerized with styrene and divinylbenzene in a suspension, yielding polymers (33–40, Scheme 3) as beads with a rather uniform particle-size distribution (150–45 μm), swellable in common organic solvents. HOCH2- and BrCH2-substituted TADDOLs were also prepared and used for attachement to Merrifield resin or to dendritic molecules (23, 26–32). The TADDOL moieties in these materials are accessible to form Ti (and Al) complexes (Scheme 4) which can be used as polymer- or dendrimer-bound reagents (stoichiometric) or Lewis acids (catalytic). The reactions studied with these new chiral auxiliaries are: enantioselective nucleophilic additions to aldehydes (of R2Zn and RTi(OCHMe2)3; Scheme 5, Table 1) and to ketones (of LiAlH4, Table 2); enantioselective ring opening of meso-anhydrides (Scheme 6); [4+2] and [3+2] cycloadditions of 3-crotonyl-1,3-oxazolidin-2-one to cyclopentadiene and to (Z)-N-benzylidenephenylamine N-oxide ( 48, 49, Scheme 7, Tables 3, 4, and Fig. 5). The enantioselectivities reached with most of the polymer-bound or dendritic TADDOL ligands were comparable or identical to those observed with the soluble analogs. The activity of the polymer-bound Lewis acids was only slightly reduced as compared with that encountered under homogeneous conditions. Multiple use of the beads (up to 10 times), without decreased performance, has been demonstrated (Figs. 3 and 4). The poorer selectivity in the Diels-Alder reaction (Scheme 7a), induced by the polymer-bound Cl2Ti-TADDOLate as compared to the soluble one, is taken as an opportunity to discuss the mechanism of this Lewis-acid catalysis, and to propose a cationic, trigonal-bipyramidal complex as the catalytically active species (Fig. 6). It is suggested that similar cations may be involved in other Ti-TADDOLate-mediated reactions as well.
190 citations
TL;DR: Using the chiral triazolium salt as a catalyst, a novel asymmetric variant of the benzoin reaction was reported in this paper, and the scope of the method was extended to a broader range of aromatic aldehydes.
Abstract: Using the chiral triazolium salt 1 as catalyst, a novel asymmetric variant of the benzoin reaction is reported. For the first time, the scope of the method is extended to a broader range of aromatic aldehydes 2, affording the acyloins 3a–h in yields of 22–72% and enantiomeric excesses up to 86%.
181 citations
TL;DR: In this article, stable carbenes derived from thiazole, 1H-imidazole, and 4H-1,2,4-triazole are efficient catalysts for benzointype condensations of formaldehyde.
Abstract: Stable carbenes derived from thiazole, 1H-imidazole, and 4H-1,2,4-triazole are efficient catalysts for benzointype condensations of formaldehyde. Catalysts derived from N-substituted thiazolium salts trimerize formaldehyde to dihydroxyacetone (II). Catalysts based on 1,4-disubstituted 4H-1,2,4-triazol-1-ium salts give glycolaldehyde (I) as the main product and no II, whereas N,N′-disubstituted 1H-imidazol-3-ium salts yield mixtures of both products. The isolation of several intermediates in the catalytic cycle provide a better insight into the reaction mechanism.
158 citations
143 citations
TL;DR: Leucascandrolide A ((+)-1), a doubly O-bridged 18-membered macrolide of a new type, was isolated from a calcareous sponge as discussed by the authors.
Abstract: Leucascandrolide A ((+)-1), a doubly O-bridged 18-membered macrolide of a new type, i.e., showing little C1-branching vs. extensive 1,3-dioxygenation and a peculiar side chain, was isolated from a calcareous sponge of a new genus, Leucascandra caveolata BOROJEVIC and KLAUTAU from the Coral Sea. Transesterification of (+)-1 gave the methyl ester 3, derived from the side chain, and the 5-hydroxy derivative (+)-2, derived from the macrolide portion and with the natural configuration at C(5) (axial). Mosher's MTPA esters 4 and 5 obtained from (+)-2 showed scattered Δδ = (δ(S) − δ(R)) data. However, inversion of the configuration at C(5) led, via ketone (+)-6, to the less encumbered 5-equatorial hydroxy derivative (+)-7, whose MTPA esters 8 and 9 gave consistent Δδ data, allowing the assignment of the absolute configuration of (+)-7, and hence of (+)-1. The structural novelty of (+)-1 and its powerful antifungal and cytotoxic activities are likely to renew interest in calcareous sponges, previously limited to scarcely biologically active 2-aminoimidazoles.
118 citations
TL;DR: In this article, the chemical structure of wine lactone was identified by high-resolution mass spectrometry (HR-MS) as 3a,4,5,7a-tetrahydro-3,6-dimethylbenzofuran-2(3H)-one.
Abstract: The intense sweet and coconut-like smelling odorant 1, named ‘wine lactone’, was isolated from different wine varieties. The chemical structure of this compound, which has not yet been detected in wine or a food, was identified by high-resolution mass spectrometry (HR-MS) as 3a,4,5,7a-tetrahydro-3,6-dimethylbenzofuran-2(3H)-one. For the evaluation of the configuration of wine lactone, stereochemically controlled syntheses were developed. All eight isomers were characterized by NMR, MS, IR, and CD measurements. The configuration of ‘wine lactone’ was in agreement with synthesized (3S,3aS,7aR)-enantiomer (1a) on the basis of enantioselective GC. For this isomer, the lowest odor threshold (0.02 pg/1 air) was detected.
113 citations
TL;DR: A number of natural polyphenols (chlorogenic acid (9), cordigol (11, cordigone (12), danthrone (1), 1,5-dihydroxy-3methoxyxanthone (2), eriosematin (7), flemichin D (8), frutinone A (6), mangiferin (4), quercetin (5), 1.3,6,7-tetrahydroxyxanthones (3) and verbascoside (10)) were investigated
Abstract: A number of natural polyphenols (chlorogenic acid (9), cordigol (11), cordigone (12), danthrone (1), 1,5-dihydroxy-3-methoxyxanthone (2), eriosematin (7), flemichin D (8), frutinone A (6), mangiferin (4), quercetin (5), 1,3,6,7-tetrahydroxyxanthone (3) and verbascoside (10)) were investigated for their redox properties using cyclic voltammetry. The antioxidant properties of these compounds were also examined in two models, namely lipid peroxidation in rat synaptosomes and AAPH-mediated oxidation of serum albumin. Compounds with a catechol group (9, 4, 5, 3 and 10) were oxidized below 0.4 V and inhibited lipid peroxidation with IC50 values between 2 and 8 mu M. Compounds having one or more isolated phenolic groups and showing an oxidation potential between 0.45 and 0.8 V (11, 12 and 8) inhibited lipid peroxidation with IC50 between 7 and 9 mu M, except 2 (0.45 V), danthrone (0.96 V) and eriosematin which showed no or modest antioxidant activity. Some of the investigated compounds also protected albumin from oxidation, but no structure-activity relationship was apparent, suggesting that other factors beside redox potential influence this activity
102 citations
TL;DR: A reinvestigation of the alkaloidal content of the roots of E. commutata showed that both elacomine and isoelacomines occur naturally in racemic form.
Abstract: Racemic elacomine ((±)-2), a hemiterpene spiro oxindole alkaloid from Elaeagnus commutata, was synthesized in five steps from 6-methoxytryptamine (19) in 16% overall yield (Scheme 3). The final oxidative rearrangement of the corresponding β-carboline precursor (±)-21 furnished isoelacomine ((±)-22) as a by-product (6% overall yield). A more elaborate route that started from L-tryptophan furnished (+)-2 and (−)-22 with optical purities of 76% (Scheme 4) and established the absolute configuration of these compounds. A reinvestigation of the alkaloidal content of the roots of E. commutata showed that both elacomine and isoelacomine occur naturally in racemic form.
TL;DR: In this paper, three macrobicyclic octamines 1−3 and the macrotricyclic hexadecamine 14 have been synthesized and three X-ray structures have been obtained, one where F− is held inside the cavity of 1− 6H+, one where Cl− is included in 3 · 6H+ and three · 6 H+ where the cavity is empty.
Abstract: Three macrobicyclic octamines 1–3 and the macrotricyclic hexadecamine 14 have been synthesized. The octamines 1–3 bind anionic substrates when protonated. The stability constants of the complexes between the protonated forms of the macrobicyclic polyamines and halide anions have been determined by pH-metric measurements. The stability constants in H2O are very high; 1 in its hexaprotonated form binds F− with high selectivity (selectivity F−/Cl− > 108), while 3 exhibits strong stability constants for both F− and Cl−. Three X-ray structures have been obtained, one where F− is held inside the cavity of 1 · 6H+, one where Cl− is included in 3 · 6H+, and 3 · 6H+ where the cavity is empty.
TL;DR: In this article, both linear ((E)-PhCHCHCHCO) and branched (CH2C(Ph)CO) unsaturated end groups were identified, and both linear (E)-PHCHCO and linear ((C-Ph(Ph)) unsaturated groups were shown to have a highly isotactic or completely atactic microstructure.
Abstract: Cationic palladium complexes 2 containing coordinated phosphino(dihydrooxazole) ligands 1 give catalytic systems which allow the production of alternating styrene-carbon monoxide copolymers. Depending on the symmetry of the ligand, the copolymers are produced either with a highly isotactic or with an essentially completely atactic microstructure. Termination of the polymeric chain is mainly due to a β-H-elimination reaction. Both linear ((E)-PhCHCHCO) and branched (CH2C(Ph)CO) unsaturated end groups were identified.
TL;DR: In this article, the treatment of artemisinin (1) and s-artemether (6) with Zn dissolving in AcOH for a few hours results in mono-deoxygenation giving deoxyartemisinIN (5) and deoxy-sartemETH (7), respectively, as the sole product.
Abstract: The treatment of artemisinin (1) and s-artemether (6) with Zn dissolving in AcOH for a few hours results in mono-deoxygenation giving deoxyartemisinin (5) and deoxy-s-artemether (7), respectively, as the sole product. In contrast, submission of 1 to FeCl2 · 4 H2O in MeCN at room temperature for 15 min causes only isomerization, (3aS,4R,6aS,7R,10S,10aR)-octahydro-4,7-dimethyl-8-oxo-2H-10H-furo[3,2-i] benzopyran-10-yl acetate (8) and (3R)-3-hydroxydeoxyartemisinin (9) being produced in 78 and 17% yield, respectively. The action of FeCl2 · 4 H2O in MeCN on 6 is similar. Under the same conditions, 6 gives products analogous to 8 and 9 accompanied by an epimeric mixture of 2-[4-methyl-2-oxo-3-(3-oxobutyl)cyclohexyl]propanaldehyde in yields of 32, 23, and 16%, respectively. No epoxide is formed on repeating the last two experiments in the presence of cyclohexene. The deoxygenation of 1 and 6 by Zn is rationalized in terms of its oxophilic nature. The catalyzed isomerization of 1 and 6 by Fe2+ is attributed to the redox properties of the Fe2+/Fe3+ system.
TL;DR: In this article, the synthesis and liquid-crystalline and thermal properties of a fullerene functionalized by a framework containing two cholesterol derivatives through a methanofullerene structure are reported.
Abstract: The synthesis and liquid-crystalline and thermal properties of a fullerene[60] functionalized by a framework containing two cholesterol derivatives through a methanofullerene structure are reported. The targeted fullerene derivative showed high thermal stability.
TL;DR: In vitro comparative cytotoxicity assays of these compounds show that for high cytotoxic activity, such as of 1in vivo, unsubstituted OHC(8a), HN(5),HN(6) moieties are needed in the natural B/D transoid configuration.
Abstract: Agelastatin A (1), an unusual alkaloid of the axinellid sponge Agelas dendromorpha from the Coral Sea, can be selectively acetylated (7) or methylated at OHC(8a) (4), peracetylated (8) or permethylated at OHC(8a), NH(5), and NH(6) (5), or, finally, subjected to C(9)C(8a) (14) or C(5b)C(8a) β-elimination (11–13), in a regiospecific manner or not, depending on the reaction conditions. Under acidic conditions, compound 12 adds H2O or MeOH, regioselectively though not endo/exo stereoselectively, giving transoid/cisoid mixtures 1/18 or 4/19, respectively. Similarly 11 or 13 add MeOH to give mixtures (−)-2/20 or 15/16, respectively. Compound 13 also adds AcOH giving mixture 8/17. The intermediate cisoid form obtained on treatment of 21 with H3O+ undergoes N(5)N(6) bridging affording pentacyclic 22 which constitutes a proof for the cisoid configuration. From conformational studies, rules are devised that allow assigning the configuration of these compounds from NMR data. In vitro comparative cytotoxicity assays of these compounds show that for high cytotoxic activity, such as of 1in vivo, unsubstituted OHC(8a), HN(5), HN(6) moieties are needed in the natural B/D transoid configuration.
TL;DR: In this article, a comprehensive series of tetraethynylethenes (TEEs) bearing electrondonating (p-methoxyphenyl or p-aminophenyl) and/or electron-accepting (p -nitrophenyl) groups was prepared via [Pd]-catalyzed Sonogashira cross-coupling reactions.
Abstract: A comprehensive series of tetraethynylethenes (= 3,4-diethynylhex-3-ene-1,5-diynes, TEEs) bearing electrondonating (p-methoxyphenyl or p-aminophenyl) and/or electron-accepting (p-nitrophenyl) groups was prepared via [Pd]-catalyzed Sonogashira cross-coupling reactions. The electronic and photonic properties of these molecules were investigated with a special emphasis on the effects caused by degree and pattern of donor/acceptor substitution around the central TEE core. This analysis showed that intramolecular donor-acceptor interactions, as evidenced by a long-wavelength charge-transfer band, are considerably more effective in TEEs 44 and 46, with trans and cis, linearly-conjugated electronic pathways between donor and acceptor, than in 11, with a geminal, cross-conjugated electronic pathway. UV/VIS Spectroscopy revealed a steady bathochromic shift of the longest-wavelength absorption band (λmax) as the number of donor-acceptor conjugation paths increased upon changing from bis-arylated (11, 44, and 46) to tetrakis-arylated (14, 31, and 35) TEEs. The position of the longest-wavelength absorption was also found to be strongly dependent on the nature of the N-substituents in the R2NC6H4-donor groups. Electronic emission spectroscopic investigations demonstrated a considerable solvent dependency of the fluorescence of donor-acceptor-substituted TEEs such as 11 or 44, in agreement with the presence of highly polarized excited states in these molecules. Correspondingly, fluorescence spectra of TEEs bearing only donor or acceptor substituents showed little solvent dependency. The large majority of the donor/acceptor-substituted TEEs are thermally and environmentally stable molecules. They can be stored for months as solids in the air at room temperature, and many decompose only upon heating to temperatures above 200°. X-Ray analysis showed the conjugated C-atom scaffolds of 44, 46, and 67 to be essentially planar, whereas the aryl substituents in 28 and 30 are rotated out of the plane of the TEE core by varying degrees.
TL;DR: In this article, the synthesis of novel 4-(phenylethynyl)pyridine subunits containing H2O-soluble complexing agents and their luminescence with EuIII ions are reported.
Abstract: The synthesis of novel 4-(phenylethynyl)pyridine subunits containing H2O-soluble complexing agents and their luminescence with EuIII ions are reported. Ligands with high luminescence intensities as well as quantum yields were obtained. Also the prepared labeling reagents as antibody conjugates gave the highest quantum and luminescence yields reported for H2O-soluble EuIII labels.
TL;DR: In this article, a cyclization of 3-hydroxybutanoic acid (3-HB) with up to 32 3-HB units, using thiopyridine activation and CuBr2 for the ring closure, produces oligolides consisting of up to 128 ring atoms.
Abstract: Monodisperse Linear and Cyclic Oligo[(R)-3-hydroxybutanoates] Containing up to 128 Monomeric Units
Using benzyl ester/(tert-butyl)diphenylsilyl ether protection, (COCl)2/pyridine esterification conditions, and a fragment-coupling strategy (with H2/Pd-C debenzylation and HF · pyridine desilylation), linear oligomers of (R)-3-hydroxybutanoic acid (3-HB) containing up to 128 3-HB building blocks (mol. weight > 11 000 Da) are assembled (Schemes 1,2,5, and 6). In contrast to the previously employed protecting-group combination, and due to the low-temperature esterifying conditions, this procedure leads to monodisperse oligomers: all steps occur without loss of single 3-HB units. The product oligomers with two, one, and no terminal protecting groups (mostly prepared in multi-gram amounts) are characterized by all standard spectroscopic methods, especially by mass spectroscopy (Figs. 2 and 3), by their optical activity, and by elemental analyses. Cyclization of the oligo[(R)-3-hydroxybutanoic acids] with up to 32 3-HB units, using thiopyridine activation and CuBr2 for the ring closure, produces oligolides consisting of up to 128 ring atoms (Scheme 7). Mixed oligolides containing 3-HB and (R)-3-hydroxypentanoic units are prepared from the corresponding linear trimers, using Yamaguchi's method for the ring closure (Scheme 8 and Fig.4 (X-ray crystal structures of two folded conformers)). Comparisons of melting points (Table 1), of [α] values (Tables 2 and 3), of 1H-NMR coupling constants (Table 3), and of molecular volume/hydroxyalkanoate unit (Table 4) of linear and cyclic oligomer derivatives and of the high-molecular-weigh polymer show that the monodisperse oligomers appear to be surprisingly good models for the polymer. Besides this insight, our synthesis is supplying the samples to further test the role of P(3-HB) (ca. 140 units) as a component of complexes forming channels through cell-wall phospholipid bilayers.
TL;DR: In this article, a series of chiral diselenides with a N-atom in the side chain was prepared by a short synthetic sequence and only 1 mol-% of them catalyzed very effectively the diethylzinc addition to various aromatic and α,β-unsaturated aldehydes yielding the secondary alcohols in up to 98% ee.
Abstract: A series of new chiral diselenides with a N-atom in the side chain was prepared by a short synthetic sequence (Scheme 1). Only 1 mol-% of these diselenides catalyzed very effectively the diethylzinc addition to various aromatic and α,β-unsaturated aldehydes yielding the secondary alcohols in up to 98% ee (Scheme 2 and Tables 1 and 2). An asymmetric amplification was observed with these catalysts. Detailed NMR studies were performed to characterize the catalytically active species.
TL;DR: In this paper, the electrochemical transfer of quinidine across the H20/I,2-dichloroethane interface was investigated by cyclic voltammetry, so as to determine its lipophilicity.
Abstract: The electrochemical transfer of quinidine across the H20/ I ,2-dichloroethane interface was investigated by cyclic voltammetry, so as to determine its lipophilicity. The formal transfer potential was measured as a function of the pH of the aqueous phase. Both singly and doubly protonated quinidine cations can transfer across the interface, and their formal Gibbs free energies of transfer were observed to be 7.7 and 31.2 kJ mol-’, respectively. Between pH 0 and 3, only the doubly charged quinidine was present in the aqueous phase and was observed to transfer. Between pH 3 and 6, the transfer of both cations occurred. The proportion of doubly charged quinidine decreased progressively in this pH range and disappeared completely above pH 6. The overall process was analyzed using a thermodynamic model. The relationship between the various forms of quinidine in both phases and pH was established and found to he in good agreement with the experimental results. With this model, the acid-base equilibrium constants in the organic phase could be calculated as pK,,, = 9.66 f 0.21 and pK,,, = 14.20 * 0.16 (the subscripts alo and a20 refer to the first and second dissociation constants). This study illustrates how the partition ofionic species can be taken into account in the determination of lipophilicity and in the description of the passive transfer of organic drugs.
TL;DR: In this article, the synthesis of C-glycosidic analogues of N4-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-L-asparagine (Asn(N4GlcNAc)) possessing a reversed amide bond as an isosteric replacement of the N-GCLN was presented.
Abstract: The synthesis of C-glycosidic analogues 15–22 of N4-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-L-asparagine (Asn(N4GlcNAc)) possessing a reversed amide bond as an isosteric replacement of the N-glycosidic linkage is presented. The peptide cyclo(-D-Pro-Phe-Ala-CGaa-Phe-Phe-) (CGaa = C-glycosylated amino acid; 24) was prepared to demonstrate that 3-[(3-acetamido-2,6-anhydro-4,5,7-tri-O-benzyl-3-deoxy-β-D-glycero-D-guloheptonoyl)amino]-2-[(9H-fluoren-9-yloxycarbonyl)amino]propanoic acid (22) can be used in solid-phase peptide synthesis. The conformation of 24 was determined by NMR and molecular-dynamics (MD) techniques. Evidence is provided that the CGaa side chain interacts with the peptide backbone. The different C-glycosylated amino acids 15–21 were prepared by coupling 3-acetamido-2,6-anhydro-4,5,7-tri-O-benzyl-3-deoxy-β-D-glycero-D-gulo-heptonic acid (4) with diamino-acid derivatives 8–14 in 83–96% yield. The synthesis of 4 was performed from 2-(acetamido-3,4,6-tri-O-benzyl-2-deoxy-β-D-glucopyranosyl) tributylstannane (2) by treatment with BuLi and CO2 in 83% yield. Similarly, propyl isocyanat yielded the glycoheptonamide 7 in 52% from 2. Compound 2 was obtained from 2-acetamido-3,4,6-tri-O-benzyl-2-deoxy-D-glucopyranose (1) by chlorination and addition of tributyltinlithium in 74% yield. A procedure for a multigram-scale synthesis of 1 is given.
TL;DR: The H2O-soluble dendritic cyclophanes (dendrophanes) 3–5 of first to third generation with molecular weights up to nearly 20 kD were synthesized, purified, and characterized, and 1H-NMR Binding titrations in borate-buffered D2O/CD3OD 1:1 showed that cyclophane-tetracarboxylate 2 forms1:1 inclusion complexes with steroids.
Abstract: The H2O-soluble dendritic cyclophanes (dendrophanes) 3–5 of first to third generation with molecular weights up to nearly 20 kD were synthesized, purified, and characterized. Cyclophane 2, which served as the initiator core (generation zero), was prepared from tetrabromocyclophane 10 in a four-step sequence which involved as the first transformation a high-yielding, four-fold Pd(0)-catalyzed Suzuki cross-coupling reaction with 4-(benzyloxy)-phenyl-boronic acid to give 18. The X-ray crystal-structure analysis of tetrabromocyclophane 10 displayed an open, nearly rectangular box with opposite aromatic walls being 8.3 and 11.4 A apart and of suitable size for the incorporation of steroidal substrates. 1H-NMR Binding titrations in borate-buffered D2O/CD3OD 1:1 showed that cyclophane-tetracarboxylate 2 forms 1:1 inclusion complexes with steroids (Table 2). Complexation was found to be enthalpically driven with higher binding affinities measured for the more apolar substrates. 1H-NMR Titrations in the same solvent also provided clear evidence for core-selective complexation of testosterone (21) by the dendrophanes 3 (1st), 4 (2nd), and 5 (3rd generation) carrying up to 108 carboxylate surface groups. The stability of the corresponding 1:1 complexes was hardly affected by the size of the dendritic shell, although some generation-dependent conformational changes in the receptor cavity seemed to take place. Remarkably, host-guest exchange kinetics in all recognition processes were fast on the 1H-NMR time scale.
TL;DR: Channel-forming activity of a pure polyester has been demonstrated for the first time and a simple model for the channel-causing structure is proposed, based on the proven tendency of oligo- and poly(3-HB) to form ca.
Abstract: Monodisperse and polydisperse oligomers and polymers of 3-hydroxybutanoic acid (3-HB) containing 8, 16, ca. 28,32, ca. 60,64,96, and ca. 3000 monomer units were incorporated into palmitoyl-oleoyl-phosphatidyl choline (POPC) planar bilayers. At concentrations of 0.1-5% of oligo(3-HB), the resulting phospholipid bilayers showed typical single-channel behavior for Rb+ and Ba2+ ions, using the patch clamp technique. Thus, channel-forming activity of a pure polyester has been demonstrated for the first time (Figs. I, 3, and 6). Single-channel activity depends upon the following structural parameters of the 3-HB derivatives: unprotected OH and COOH groups on the chain ends; chain length 2 16 monomer units; no high-molecular-weight as in P(3-HB). The results are discussed in view of the Ca2+-specific channel formed with the P(3-HP)/Ca .PP, complex from genetically com- petent Escherichiu coli and in view of the ubiquitous occurrence of low-molecular-weight P(3-HB) in prokaryotic and eukaryotic organisms. A simple model for the channel-causing structure is proposed, based on the proven tendency of oligo- and poly(3-HB) to form ca. 50-8, thick lamellar crystallites. 1. Introduction. - Poly((R)-3-hydroxybutanoate) (P(3-HB)) is a stereoregular poly- ester produced as a storage material by prokaryotic microorganisms under growth-limit- ing conditions. It can accumulate in quantities of up to 90% of the cell dry mass and usually has a molecular weight of ca. lo5 to lo6 g/mol (l). Since its discovery by Lemoigne cu. 70 years ago (2), P(3-HB) and related poly@ -hydroxyalkanoates) have attracted growing interest both in academia and industry (3). The main reason for the interest in these polymers is their biocompatibility and biodegradability which allows them to be used as biodegradable substitutes for conventional plastics3). The biosynthesis of high-molecular-weight P(3-HB) in Alcaligenes eutrophus has been the subject of the most intensive studies. The enzymes involved have been identified and expressed in other microorganisms and even in plants using genetic technology IS). The P(3-HB) accumulation in the microorganism begins when the limitation of certain nutri- ents occurs, and carbon sources are available in excess. Degradation is initiated if
TL;DR: In this paper, the structure of the duplex formed by self-pairing of the p-RNA octamer b-D-ribopyranosyl-(2'->4')-(CGAATTCG) was studied by NMR techniques and independently by mol-dynamics calcns.
Abstract: The soln. structure of the duplex formed by self-pairing of the p-RNA octamer b-D-ribopyranosyl-(2'->4')-(CGAATTCG) was studied by NMR techniques and, independently, by mol.-dynamics calcns. The resonances of all non-exchanging protons, H-bearing C-atoms, P-atoms, and of most NH protons were assigned. Dihedral angle and distance constraints derived from coupling consts. and NOESY spectra are consistent with a single dominant conformer and corroborate the main structural features predicted by qual. conformational anal. The duplex displays Watson-Crick pairing with antiparallel strand orientation. The dihedral angles b and e in the phosphodiester linkages differ considerably from the idealized values. Model considerations indicate that these deviations from the idealized model allow better inter strand stacking and lessen unfavorable interactions in the backbone. The av. base-pair axis forms an angle of ca. 40 Deg with the backbone. The resulting inter strand p-p stacking between either 2 purines, or a purine and a pyrimidine, but not between 2 pyrimidines, constitutes a characteristic structural feature of the p-RNA duplex. A 1000-ps mol.-dynamics (MD) calcn. with the AMBER force field resulted in an av. structure of the same conformation type as derived by NMR. For the backbone torsion angle e, dynamically averaged coupling consts. from the MD calcn. agree well with the exptl. values, but for the angle b, a systematic difference of ca. 25 Deg remains. The 2 base pairs at the ends of the duplex are calcd. to be highly labile, which is consistent with the high exchange rate of the corresponding imino protons found by NMR. [on SciFinder (R)]
TL;DR: The oligonucleotide building blocks and the phosphoramidites derived from 7-iodo- and 7-bromo-7-deaza-2′-deoxyguanosines 3a, b were prepared and correlated to the major-groove modification of this DNA.
Abstract: The oligonucleotide building blocks, the phosphonates 1a, b and the phosphoramidites 2a, b derived from 7-iodo- and 7-bromo-7-deaza-2′-deoxyguanosines 3a, b were prepared. They were employed in solid-phase oligonucleotide synthesis of the alternating octamers d(Br7c7G-C)4 (8) and d(I7c7G-C)4 (9) as well as the homo-oligonucleotides d[(Br7c7G)5-G] (11) and d[(I7c7G)5-G] (12). The melting profiles and CD spectra of oligonucleotide duplexes were measured. The Tm values as well as the thermodynamic data were determined and correlated to the major-groove modification of this DNA. The self-complementary octamers 8 and 9 form more stable duplexes compared to the parent oligomer d(G-C)4. The heteroduplex of d[(I7c7G)5-G] (12) with d(C6) is slightly destabilized (ΔTm = −12°) over that of d[(c7G)5-G] with d(C6). However, the complex of 12 with poly(C) is more stable than that of d[(c7G5-G)] with poly(C).
TL;DR: In this paper, two synthetic pathways towards 4′-C-acylthymidines are presented, where modified mononucleosides are precursors of the 2′-deoxyribonucleotide 4′−C-radical.
Abstract: Two synthetic pathways towards 4′-C-acylthymidines are presented. These modified mononucleosides are precursors of the 2′-deoxyribonucleotide 4′-C-radical. They were converted into their corresponding 3′-O-[(2-cyanoethyl) N,N-diisopropylphosphoramidites] 3a–c and incorporated in oligonucleotides by solid-phase synthesis. The structure of some modified nucleosides was revealed by X-ray crystal-structure analysis.
TL;DR: In this article, the synthesis of the linear tris[terpyridine] 1 with three tridentate binding sites is described, and the reaction with metal ions of octahedral coordination geometry, such as FeII or NiII, leads to the self-assembly of trinuclear complexes [M3(1)2]6+, which display properties in agreement with a double helical structure.
Abstract: The synthesis of the linear tris[terpyridine] 1 with three tridentate binding sites is described. The reaction with metal ions of octahedral coordination geometry, such as FeII or NiII, leads to the self-assembly of trinuclear complexes [M3(1)2]6+, which display properties in agreement with a double helical structure. The trinuclear iron (II) helicate has been resolved into its enantiomers.
TL;DR: In this article, the authors showed that in the reduction of α,β-unsaturated sulfones, the highest enantioselectivities were obtained with unsymmetrical ‘semicorrins, whereas in all other cases C2-symmetric ‘semiorins’ proved to be superior.
Abstract: ‘Semicorrin’ cobalt complexes, prepared in situ from cobalt(II) chloride and the corresponding ligands, are efficient catalysts for the enantioselective reduction of electrophilic CC bonds with NaBH4. The best selectivities (> 90% ee) are achieved with α,β-unsaturated carboxamides and carboxylates. Analogous α,β-unsaturated nitriles, sulfones, and phosphonates afford enantiomeric excesses of 50–70%. Interestingly, in the reduction of α,β-unsaturated sulfones, the highest enantioselectivities were obtained with unsymmetrical ‘semicorrins’, whereas in all other cases C2-symmetric ‘semicorrins’ proved to be superior.
TL;DR: The triazoles 17 and 18 have been prepared in six steps from the L-xylofuranose 21 and possess a CH group instead of the N-center of the related tetrazoles 4 and 5, corresponding to the glycosidic O-atom, and a very similar structure, both in solution and in the solid state.
Abstract: The structure of the β-glycosidase inhibitors 1–7 and 10–13 suggests that protonation of O–C(1) (the glycosidic O-center) of the substrate by a carboxy group of the retaining β-glycosidases does not occur in the plane perpendicular to the ring of the glycon (β-side; ‘from the top’), but in the plane of the ring (‘from the side’). The triazoles 17 and 18 have been prepared in six steps from the L-xylofuranose 21. They possess a CH group instead of the N-center of the related tetrazoles 4 and 5, corresponding to the glycosidic O-atom, and a very similar structure, both in solution and in the solid state. Unlike the tetrazoles, however, which are good-to-medium inhibitors of retaining β-glycosidases, the triazoles do not inhibit the β-glycosidases from sweet almonds, snail, and bovine liver, and only slightly inhibit the β-glucosidase from Caldocellum saccharolyticum. This is in keeping with the proposed direction of protonation in the plane of the saccharide ring and with modelling studies, docking 4 into the active site of the white clover cyanogenic β-glucosidase and 6 into the E. coli β-galactosidase and the Lactococcus lactis 6-phospho-β-galactosidase.