Showing papers in "Liebigs Annalen in 1995"

Progress towards a generalized solvent polarity scale: The solvatochromism of 2-(dimethylamino)-7-nitrofluorene and its homomorph 2-fluoro-7-nitrofluorene

Abstract: More than 100 solvents and the gas phase were used to develop a solvent dipolarity-polarizability scale that combines the medium dipolarity and polarizability into a single parameter (SPP) calculated from the UV-visible spectra of 2-(dimethyl-amino)-7-nitrofluorene (DMANF) and its homomorph 2-fluoro-7-nitrofuorene (FNF). The proposed scale compares favourably for nonprotic solvents with existing solvent polarity scales including Kosower's Z, Dimroth and Reichardt's ET(30), Brooker's χR, Dong and Winnick's Py; Kamlet, Abboud, and Taft's π*, and Drago's S′ scale. When data are derived from electronic transitions, they provide an accurate description for the solvent effect in UV-Vis, IR, NMR, and fluorescence spectroscopy as well as in other chemical areas including thermodynamics and kinetics.

Synthesis of perylene‐3,4‐dicarboximides — Novel highly photostable fluorescent dyes

Abstract: Perylene-3,4-dicarboximides 2 are obtained by a decarboxylizing condensation of moderately sterically hindered primary amines with perylene-3,4,9,10-tetracarboxylic 3,4:9,10-bisanhydride (3) in the presence of water. Perylene-3,4-dicarboxylic anhydride (4) is prepared by hydrolysis of the imides with KOH in tert-butyl alcohol. The anhydride may be condensed with any primary amine to the corresponding imide. The imides are highly fluorescent and very photostable dyes.

Structure elucidation of yersiniabactin, a siderophore from highly virulent Yersinia strains

Abstract: From cultures of Yersinia enterocolitica H1852, an iron-complexing and iron-transporting compound named yersiniabactin was isolated. The structure of the siderophore was determined by a variety of spectroscopic methods, including 2D NMR experiments on the metal-free ligand as well as its gallium complex. The metal-free ligand, derivatives, as well as iron and gallium complexes were examined by high-resolution FAB-MS, API-MS, API-MS/MS and GC-MS. The novel siderophore contains a benzene and a thiazolidine ring, as well as two thiazoline rings (Figure 1). Its stereochemistry is noteworthy for the presence of five chiral centers, one of which is considerably epimerized. The compound forms stable complexes with trivalent cations such as ferric iron and gallium.

On the preparation of β-amino acids from α-amino acids using the Arndt-Eistert reaction: Scope, limitations and stereoselectivity. Application to carbohydrate peptidation. Stereoselective α-alkylations of some β-amino acids

Abstract: The Arndt-Eistert homologation of α-amino acids was studied to determine the stereoselectivity in this reaction by chromatographic up-to-date analytical methods. While carba-mate-protected phenylglycine was transformed to the corresponding β-amino acid methyl ester with a stereoselectivity of only 9:1, all other tested amino acid derivatives (Ala, Phe, Ser, Orn, tert-Leu and perhydro-azepine-2-carboxylic acid, suitably protected) were homologated with full retention of configuration (products 9–17). The intermediate diazo ketones 1–8 were purified and characterized by their NMR spectra. When nucleophiles derived from partially protected sugars were present during decomposition of the diazo ketones (derived from amino acids or dipeptides), a strong dependence of the yield (products 21–24) on the degree of steric hindrance of the nucleophilic OH group was observed. Two of the β-amino acids obtained from the homologation reaction were transformed to α-substituted (25–27, 31, 32) and α,α-disubstituted β-amino acid derivatives (28, 29) with excellent selectivities (in most cases, a single diastereoisomer was obtained).

Molecular modeling of saccharides, 7. The conformation of sucrose in water: A molecular dynamics approach†

Abstract: A molecular mechanics analysis of the conformational properties of sucrose in vacuo in terms of the intersaccharidic torsion angles Φ and Ψ, revealed three energy minima. The geometry of the global minimum-energy closely resembles the solid-state structure. Most notably, the interresidue hydrogen bonding interaction 2g-O…HO-1f present in the crystal, is retained under vacuum boundary conditions, indicating the molecular geometries adopted in the crystal lattice and in vacuo to be similar. For aqueous solutions, detailed molecular dynamics simulations of sucrose „soaked” with 571 water molecules in a periodic box (truncated octahedron), revealed this direct H-bond interaction to be replaced by an indirect, water-mentioned one: an interresidue water-bridge of the 2g-O…H2O…HO-1f type prevailed with a high significance and a long life-time. This means the linkage geometry of sucrose in water–despite the absence of direct interresidue hydrogen bonds–again closely resembles the solid-state and in vacuo geometry in terms of the orientation of the glucose and the fructose unit relative to one another. The solution dynamics of, and the hydration around sucrose were analyzed in terms of pair distribution functions. These indicate strong hydrogen bonding between all sucrose hydroxyls (as donors and acceptors) and water within a first, well-defined hydration layer (hydroxyl-oxygen–water distances 1.8–3.5 A), whereas the acetalic oxygens are engaged to a lesser extent as H-bond acceptors. The second hydration shell (>4 A) is rather diffuse and less pronounced, indicating those water molecules to be in a disordered state. The implications of the hydration shell and the water bridge on the crystallization process of sucrose and on binding towards transporter proteins, and the sweet-taste receptor, are discussed. Other sucrose conformations that may conceivably exist in aqueous solution, may have eluded the MD simulation search. The umbrella sampling technique was applied for establishing the free energy profile as a function of the intersaccharidic torsion angles. The resulting concise picture of the dynamics of sucrose in aqueous solution, encompassing the entire conformational space available, revealed only two energy minima. Of these, the by far, most populated global minimum structure corresponded to the most stable solution geometry, as found by molecular dynamics.

Influence of substituents on the rotational energy barrier of atropisomeric biphenyls — studies by polarimetry and dynamic gas chromatography

Abstract: We have synthesized a series of 2,2′-substituted biphenyls and particularly derivatives of 2,2′-bis(trifluoromethyl)biphenyl (4) with either one or two fluoro, chloro, bromo, amino, nitro or methoxy substituents in the para positions for investigating the influence of these substituents on the rotational energy barrier of the biphenyls by polarimetry and dynamic gas chromatography (DGC). Axially chiral biphenyls with at least two bulky substituents in the ortho positions were separated by gas chromatography on selectively modified cyclodextrins. Due to competition between resolution and enantiomerization in the gas chromatographic column 2-tert-butyl-2′-isopropyl- (2), 2-isopropyl-2′-(trifluoromethyl)biphenyl (5), and some para-substituted derivatives of 4 show temperature-dependent interconversion profiles and coalescence phenomena in analogy to dynamic NMR studies. The accelerating effect on the rate of enantiomerization of electron-donating groups in the para positions and the decelerating effect of electron-accepting groups has been determined. Dynamic gas chromatography is shown to be a useful supplement to studies of thermal enantiomerization kinetics of optically enriched or separated compounds by polarimetry for the investigation of energy barriers of atropisomeric biphenyls.

Marine bacteria, VIII. Maremycin A and B, new diketopiperazines from a marine Streptomyces sp.

Abstract: In the culture broth of the marine Streptomyces sp. B 9173 the two novel diketopiperazines maremycin A (1) and B (2) were detected by chemical screening. Their structures were elucidated and confirmed by the synthesis of the oxindole derivative 4.

Solvent dipolarity/polarizability (SPP) of alcoholic solvents

Abstract: The positive solvatochromism exhibited by 2-(dimethylamino)-7-nitrofluorene (DMANF) and 2-fluoro-7-nitrofluorene (FNF) was used to determine the solvent dipolarity/polarizability (SPP) of 29 saturated aliphatic alcohols, four unsaturated alcohols, an aromatic alcohol, a triol, and water. The SPP values for the alcohols lie at the top of the SPP solvent polarity scale. The SPP values for n-alkanols decreases with increasing chain length, in contrast to the behavior of n-alkanes. On the other hand, the polarity of n-alkanols, like that of n-alkanes, increases on cyclization. The polarity of m-cresol (1.0) and of 1,1,1,3,3,3-hexafluoro-2-propanol (1.007) places these solvents at the top of the SPP scale.

Chiral calixarenes derived from resorcinol

Abstract: A new type of chiral resorc[4]arene is described. The formation of both enantiomers of 5 is controlled by the chirality of the amines used in the Mannich reaction leading to the 1,3-oxazine ring anellated to the resorcarene moiety. At -50 degrees C ee increases up to 90 %. Both enantiomers can be easily purified to >98% ee by recrystallization. The structures were proved by standard methods including X-ray analysis.

Perylenamidine‐imide dyes

Abstract: Perylene-3,4:9,10-tetracarboxylic acid 3,4-anhydride-9,10-imides are condensed with primary diamines to a number of new basic chromophores with amidine-imide structures. Lightfast dyes are obtained which exhibit a strong fluorescence in solution. The absorption and fluorescence spectra of the title compounds are bathochromically shifted compared to those of the perylene dyes.

Synthesis of phthalocyanines with one sulfonic acid, carboxylic acid, or amino group

Abstract: Monofunctional phthalocyanines 7a,b, one bearing a sulfo and the other one a carboxyl group, were synthesized by lithium alkoxyde-catalyzed statistical tetramerization of 4-(4-tert-butylphenoxy)-1,2-benzenedicarbonitrile (3c) with 1,2-dicyanobenzenes 3a,b carrying a carboxyl or sulfo group. Tribenzonaphthoporphyrazines 9a,b with one carboxyl or amino group were prepared under similar reaction conditions by tetramerization of 3,6-dihexyloxy-1,2-benzenedicar-bonitrile with 6-amino- or 6-carboxy-2,3-naphthalenedicar-bonitrile 6b,6a. The zinc(II)-containing macrocycles 7a, b, 9a, b obtained in yields of 11–20% were purified by column chromatography and characterized by UV/Vis, mass, and 1H-NMR spectroscopy.

Template synthesis of the first amide-based rotaxanes

Abstract: The first rotaxanes 6a, 6b and 11 with an amide structure are described. Their (supramolecular template) syntheses are strikingly simple. The central part of the „axle” is added to the „wheel” and subsequently capped. The macromonocycle („wheel”) provides the receptor cavity for the „axle” and the triphenylmethane stoppers confirm the mechanical bond between „wheel” and „axle”.

Synthesis of 5,8‐dimethoxy‐2(1H)‐quinolinones by intramolecular Wittig reaction

Abstract: The title compounds 12, which are key intermediates for antitumoral diazaquinomycin A analogues, are obtained by intramolecular Wittig reaction of 1‐[3′,6′‐dimethoxy‐2′‐(α‐oxoacylamino)phenyl]alkyltriphenylphosphonium salts 11, which are prepared via lithiation of 2′,5′‐dimethoxy‐N‐pivaloylaniline 6. The applicability of this route to polysubstituted 2(1H)‐quinolinones 12 and 17 is examined. Copyright © 1995 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim

Enantioselective reformatsky reaction of methyl bromodifluoroacetate

Abstract: The Reformatsky reagent 2 generated from methyl bromodifluoroacetate is added to benzaldehyde in the presence of carbinols 3a, b, amino alcohols 3c-g, or amino alkoxide 3h. N-Methylephedrine 3c provides the highest enantioselectivity in the formation of the adduct S-4a (84% ee; >96% after recrystallization) whose absolute configuration is determined by an X-ray structural analysis of the amide 6.

Cinnolines and pyrazolopyridazines. — Novel synthetic and mechanistic aspects of the Richter reaction

Abstract: The thermal cyclization of 2-alkynylbenzenediazonium salts 2 known as the Richter reaction and leading, as described in the literature, only to 4-hydroxycinnolines 6 has been studied. A new probable route to these compounds involving intermediate formation of the 4-chlorocinnolines 4 followed by hydrolysis of the latter to 6 is discussed. A new understanding of the reaction mechanism has induced us to change the reaction conditions in order to synthesize some 4-bromo- (5), 4-chloro- (4), and 4-hydroxycinnolines 6 as well as 4-bromo-(8b) and 4-chloropyrazolopyridazine 8a.

Glycosyl imidates, 69. Synthesis of flavone C‐glycosides vitexin, isovitexin, and isoembigenin

Abstract: 2-Hydroxy-4,6-dimethoxyacetophenone (4) was glycosylated with O-(2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl) trichloroacetimidate (5) and trimethylsilyl triflate as promoter to yield directly the C-glycoside 6. Construction of the flavone system by application of a Baker-Venkataraman-type rearrangement followed by deprotection yielded isoembigenin (2). Glycosylation of 4,6-bis(tert-butyldimethylsilyloxy)-2-hydroxyacetophenone (17) with the trichloroacetimidate 5 afforded the O-glycoside intermediate 18 which was converted via Fries rearrangement into the C-glycoside 21. Applying again the Baker-Venkataraman rearrangement and cyclization gave isovitexin and vitexin derivatives 25 and 26, which were completely deprotected to yield isovitexin (1b) and vitexin (1a), respectively.

Chiral organometallic reagents, XII. On the racemization of α-hetero-substituted benzyllithium compounds

Abstract: Benzyllithium compounds carrying a benzylthio substituent (6), a benzylseleno substituent (8), and an isopropyl(methyl)amino substituent (14) have been generated. Racemization barriers have been determined in THF by monitoring the coalescence of signals of diastereotopic groups in the 1H-NMR spectra. The barrier for 6 amounts to a ΔH≠ of 7.5 kcal mol−1 and ΔS≠ of −12 cal mol−1 K−1 corresponding to a ΔG of 9.9 kcal mol−1. The barrier for the other compounds investigated varies from 9 to 10 kcal mol−1. The rate-determining step for the racemization is discussed to be the transformation of the contact ion pair to the solvent-separated ion pair.

Antibiotics from Gliding Bacteria, LXIII. Ratjadone: A New Antifungal Metabolite from Sorangium cellulosum

Abstract: The antifungal metabolite ratjadone (1) was isolated from the myxobacterium Sorangium cellulosum, strain So ce360. Production was achieved by fermentation in the presence of the adsorber resin XAD-16, extraction and separation by RP chromatography. The structure of 1 was determined by spectroscopic methods. It is characterized by a 4-hydroxytetrahydropyran and a 5,6-dihydropyran-2-one ring which are connected by an unsaturated C11 carbon chain. The polyketide origin of 1 was proven by feeding experiments with 13C-labeled precursors and NMR spectroscopic examinations.

Planar chiral systems, IV. An efficient route for the preparation of 5‐formyl‐4‐hydroxy[2.2]paracyclophane (FHPC)

Abstract: For the preparation of the title compound, 4-hydroxy[2.2]paracyclophane (1) is first converted to the carbamate 2. Metalation of 2 with sec-butyllithium yields an ortho-anion which after trapping with dimethylformamide and acidic work-up provides 6 in 64% yield. Further application of the cyclophane anion include its capture by trimethylsilyl chloride to the trimethylsilyl derivative 3 (76%) and its Fries rearrangement to the phenol 4 (78%). The spectroscopic and analytical data of the new compounds are described in full detail.

New alkaloids from ants: Identification and synthesis of (3R,5S,9R)-3-butyl-5-(1-oxopropyl)indolizidine and (3R,5R,9R)-3-butyl-5-(1-oxopropyl)indolizidine, constituents of the poison gland secretion in Myrmicaria eumenoides (hymenoptera, formicidae)†

Abstract: The (3R,5S,9R) and (3R,5R,9R) stereoisomers of 3-butyl-5-(1-oxopropyl)indolizidine (9) were identified as major constituents of the poison gland secretion of the African ant, Myrmicaria eumenoides. Racemates of the four diastereomers of 9 were synthesized via the corresponding ethyl 5-(5-butylpyrrolidin-2-yl)pentanoates (6). Enantiomerically pure samples of the (3R)-stereoisomers of 9 were obtained by starting from (2R)-2,3-O-isopropylideneglyceric aldehyde (21) and 6-methylpyridine-2-carboxaldehyde (20). In addition, the enantiomeric separation by chiral gas chromatography and unambiguous structure assignment of the target compounds are described.

Reaktionen von Diaminen mit Fulleren C60

Abstract: Reactions of Diamines with Fullerene C60 Reactions of 1,2- and 1,3-diamines 2a-i, including diamines containing primary amino groups, with C60 (1) in toluene are described, leading to mono- and bisadducts 3–16. In this way fullerene derivatives carrying NH as a nucleophilic functional group have been synthesized. Yields and ratios of mono- and bisadducts formed depend on reaction conditions and on the structure of the diamine. The scope of this reaction leading to defined mono- and bisadducts in appreciable yields has been investigated. Mono- and bisadducts formed can be separated by column chromatography on SiO2. Mass and NMR spectra reveal that the isolated basic fullerene derivatives are dehydro adducts. NMR spectra show that the monoadducts have a symmetrical structure. In all cases investigated the addition forming the mono- and bisadducts of 1 occurs across a 6–6 bond. Likewise analogous additions take place with C70. Remarkably, tertiary diamines such as 2p and q react with 1 forming the monoadduct 8 in small yields by loss of an alkyl group. Proposed structures of some regioisomeric bisadducts are discussed.

Molecular modeling of saccharides, 6. Small‐ring cyclodextrins: Their geometries and hydrophobic topographies

Abstract: A detailed force-field-based evaluation of the molecular geometries of small-ring cyclodextrins 1–3 with three, four, and five α(14)-linked glucose residues and the starch-derived α-cyclodextrin (4) was performed by using molecular mechanics and high-temperature annealing. The resulting minimum-energy structures reveal that the progressive strain imposed by diminution of the cyclodextrin macrocycle from six glucose units (α-CD, 4) to five (cycloglucopentaoside 3), four (tetraoside 2), and three (cyclotrioside 1) is reflected in a widening of the intersaccharidic bond angle, in a complex balance of the interrelated glucose tilt angles τ and the glycosidic torsions Φ and Ψ against each other, and most strikingly, in a specific unilateral distortion of the pyranoid rings, i.e. flattening at C-4 towards the E1 envelope conformation. This successive levelling at C-4, induced by a decrease of the two related ring torsion angles, is small in the pentamer 3, pronounced in 2, and fully realized in the cyclotrioside 1. – The respective contact surfaces of the minimum-energy conformers and their molecular lipophilicity patterns (MLP), in color-coded form, were also generated, allowing an assessment of their capabilities to form inclusion complexes. Accordingly, only the cyclopentaoside 3 exhibits a hydrophobic central cavity similar to that of α-CD (4), the smaller cyclodextrins 2 and 1 are closed, yet contain a hydrophobic indentation for potential binding.

Synthesis of sphingosines, 11. Convenient synthesis of phytosphingosine and sphinganine from D‐galactal and D‐arabitol

Abstract: 3,4,6-Tri-O-benzyl-D-galactal (3) was directly converted into 3,4,6-tri-O-benzyl-2-deoxy-D-galactose (5). Wittig reaction of 5 with alkyltriphenylphosphonium salts in the presence of n-butyllithium as the base afforded olefins 6a, b which could be readily transformed into phytosphingosines 1a, b via different routes: (i) at first azido group introduction and then double bond and protective group removal, and azido group generation via hydrogenation; (ii) 2-O-mesylation, then double bond and benzyl group removal via hydrogenation, and finally nitrogen introduction; (iii) selective double bond hydrogenation, then nitrogen introduction, and finally benzyl group removal and amino group generation via hydrogenation. Wittig reaction of 5 with alkyltriphenylphosphonium salt in the presence of potassium tert-butoxide as the base afforded diene 7a which proved to be a convenient precursor for sphinganine syntheses; thus, 2-O-mesylation, then double bond and benzyl group removal via hydrogenation and 1,3-O-acetylation, and finally nitrogen introduction and de-O-acetylation afforded 23a. Based on the convenient transformation of D-arabitol into the 1,3-O-benzylidene derivative 25 a further phytosphingosine synthesis is outlined.

Functional dyes for molecular switching. Dihydroazulene/vinylheptafulvene photochromism: Effect of π-arylenes on the switching behavior

Abstract: The reversible interconversion of dihydroazulene (DHA) and vinylheptafulvene (VHF) can be utilized to switch a number of physical properties. This communication reports on a fluorescent switch. By a multistep sequence involving an [8 + 2] cycloaddition route 9-anthracenyl-1,4-phenylene was covalently attached to C-2 of the DHA chromophore affording DHA-1 which undergoes complete and clean photochemical ring opening to vinylheptafulvene VHF-1. The latter is thermally reverted to DHA-1. The kinetics and the energetics of the thermal back reaction are discussed. On/off switching of luminescence was investigated: DHA-1 displays fluorescence whereas VHF-1 is nonfluorescent at ambient temperature.

Prearranged glycosides, 2. Intramolecular glycosylation of prearranged saccharides as a novel strategy for the construction of β-L-rhamnosidic linkages

Abstract: Disaccharides containing a β-L-rhamnosyl residue were prepared by a novel intramolecular glycosylation strategy. Thus, suitably benzyl-protected L-rhamnosyl donors (ethyl and phenyl 1-thiorhamnoside 7, 18) were prearranged in positions 2 and 3 with benzyl 2-O-benzoyl-4,6-O-benzylidene-α-D-glucopyranoside 8 in position 3 by a malonyl, succinyl and phthaloyl bridge, respectively, to give the corresponding connected saccharides 9, 12, 16 and 20. After regioselective opening of the benzylidene ring of the glucoside residue to give compounds 10, 13, 17 and 21, the latter afforded the 3,2′- and 3,3′-bridged disaccharides 22–25 upon intramolecular glycosylation with a thiophilic reagent. The anomeric selectivity of this intramolecular glycosylation is strongly influenced by the nature of the alkanoyl and aroyl bridge, its position at the rhamnosyl residue and the solvent used for the coupling. Best results were obtained in acetonitrile with the succinyl „spacer” attached to position 2 of the phenyl 1-thiorhamnoside and position 3 of the glucoside that afforded the corresponding β-(14)-linked disaccharide 22β in 76% yield.

Azobenzene-Based Photoswitchable Catenanes

Abstract: Four catenanes (1–4) and the corresponding tetracationic monocycles 5–8 are synthesized. X-ray structural analyses allow a prediction of the mobility (circumrotation) of the „interlocked” rings in the catenanes, which is proven by 1H-NMR spectroscopy. An unexpected order in the crystal packing of 6 is demonstrated. (E/Z) isomerization in one ring influences the second ring of 1–4 and inversely. An existing obstacle inside the cavity of the switchable macrocycle can block this isomerization completely.

Pyridinium N‐phenoxide betaines and their application to the characterization of solvent polarities, XXI Determination of new and corrections of old ET(30) values as empirical measures of solvent polarity for 40 organic solvents

Abstract: By means of the negative solvatochromic betaine dyes 1a and 1b empirical solvent polarity parameters ET(30) for 40 organic solvents of current interest were newly determined or corrected (Table 1).

Radikal-Stabilisierungsenergie – das MMEVBH-Kraftfeld

Abstract: Radical-Stabilization-Energy – the MMEVBH Force Field Making use of the VB method of Malrieu et al.[6–10] a force field has been developped, which allows to calculate heats of formation of hydrocarbons (conjugated and non-conjugated olefins, radicals, and diradicals) with high accuracy. With this method radical stabilization energies (RSE) for a great number of delocalized radicals are calculated and compared with experimental values, derived from shock-tube measurements of dissociation energies or from rotational barriers of substituted olefins. A detailed analysis of the RSE with respect to structure, substituents, strain, and aromaticity is presented.

Pseudosugars, 35. Synthesis of glycosylceramide analogs composed of imino-linked unsaturated 5a-carbaglycosyl residues: Potent and specific gluco- and galactocerebrosidase inhibitors

Abstract: 5a-Carba-β-glucosyl- E-3 and galactosylceramide analogs E-4 were synthesized by coupling of the protected derivatives 5 of β-valienamine and 15 of 4-epi-β-valienamine with the aziridines E-6 and Z-6, as the sphingosine precursors, respectively, and subsequent deprotection and N-acylation. Both the new analogs and their corresponding Z-isomers Z-3 and Z-4 were shown to be very potent and specific gluco- and galactocerebrosidase inhibitors, and, interestingly, the Z-isomers possess inhibitory activity comparable to that of the corresponding E-isomers.

Sulfonamide‐based catenanes — regioselective template synthesis

Abstract: The first catenanes containing sulfonamide units were synthesized. Selective formation of the in/out isomer 7 can be explained by host-guest interactions that cause a regioselective templating effect. Replacement of O2S-NH by O2S-NMe increases the yield significantly (from 10 to 19%). The sulfonamide catenane 7 has a topologically chiral structure.