Bibliothek

Notizen: The reaction of 4-hydroxycoumarin and certain aliphatic aldehydes affords 1:1 or complex 2:2 adducts besides (or in place) of the expected 2:1 bis(coumarin) adducts. Reaction with heptanal, cyclohexanecarbaldehyde, and pivalaldehyde are reported as representative. The structure of the reaction products was established by spectroscopical techniques, including X-ray analysis, and their formation was mechanistically rationalized. Some of the 1:1 adducts are synthetically useful for the preparation of 3-alkyl-4-hydroxycoumarins.

Notizen: 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.

Notizen: From the aerial parts of Scrophularia ilwensis, four new triterpene saponins, ilwensisaponins A-D (1-4) were isolated. The structures of the compounds were elucidated using chemical and spectral data as 13β, 28-epoxy-3-β-{{[β-D-glucopyranosyl-(1→2)]-[α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranosyl-(1→3)]-β-D-fucopyranosyl}-oxy} olean-11-en-23-ol (1), 3-β-{{[β-D-glucopyranosyl-(1→2)]-[α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranosyl-(1→3)]-β-D-fucopyranosyl}oxy}olena-11, 13(18)-diene-23, 28-diol (2), 3-β-{{[β-D-glucopyranosyl-(1→2)]-[α-L-rhamnopyranosyl-(1→4)-β-Dglucopyranosyl-(1→3)]-β-Dfucopyranosyl}oxy}-11α-methoxyolean- 12-ene-23, 28-diol (3), and 3-β-{{[β-D-glucopyransoyl-(1→2)]-[α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranosyl-(1→3)]-β-D-fucopyranosyl}oxy}olean-12-ene-11α,23,28-triol(4).

Notizen: Prelactones C (3) B (8) were isolated from the concanamycin-producing Streptomyces sp. (strain Gö 22/15) and bafilomycin-producing Streptomyces griseus (strain Tü 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.

Notizen: It is shown that azulene (1) and dimethyl acetylenedicarboxylate (ADM) in a fourfold molar excess react at 200° in decalin to yield, beside the known heptalene- (5) and azulene-1,2-dicarboxylates (6), in an amount of 1.6% tetramethyl (1RS,2RS,5SR,8RS)-tetracyclo[6.2.2.22,501,5]tetradeca-3,6,9,11,13-pentaene-3,4,9,10-tetracarboxylate(‘anti’-7) as a result of a SHOMO (azulene)/LUMO(ADM)-controlled addition of ADM to the seven-membered ring of 1 followed by a Diels-Alder reaction of the so formed tricyclic intermediate 16 (cf. Scheme 3) with a second molecule of ADM. The structure of ‘anti’-7 was confirmed by an X-ray diffraction analysis. Similarly, the thermal reaction of 5,7-dimehtylazulene (3) with excess ADM in decalin at 120° led to the formation of ca. 1% of ‘anti’- 12, the 7,12-dimethyl derivative of‘anti’-7, beside of the corresponding heptalene- 10 and azulene-1,2-dicaboxylated (cf Scheme 2). The introduction of Me groups at C(1)and C(3)of azulene (1) and its 5,7-dimethyl derivative 3 strongly enhance the thermal formation of the corresponding tetracyclic compound. Thus, 1,3-dimethylazulene (2) in the presence of a sevenfold molar excess of ADM at 200° yielded 20% of ‘anti’-9 beside an equal amount of dimethyl 3-mehtylazulene-1,2-dicarboxylate (8;cf. Scheme 1), and 1,3,5,7-tetramethylazulene (4) with a fourfold molar excess of ADM AT 200° gave a yield of 37% of‘anti’-15 beside small amount of the corresponding heptalene- 13 and azulene-1,2-dicarboxylates 14 (cf.Scheme 2).

Notizen: The para-substituted tridentate ligands 2,6-bis[1-(3,5-dimethoxybenzyl)benzimidazol-2-yl]-4′-X-phenyl)-pyridine (X = H: L3; X = NO2: L4; X = NEt2: L5) have been synthesized in six steps using Kröhnke reactions. Spectroscopic results show that the electronic properties of the ligands are strongly influenced by the nature of the substituent bound to the pyridine ring and extended Hückel calculations performed on 4-(X-phenyl)pyridine fragments give a qualitative insight into the factors responsible for the striking differences observed in the absorption spectra. Upon complexation to FeII, the ligands L2-L5 give intensely coloured pseudo-ocatahedral low spin [Fe(Ln)2]2+ (n = 2-5) complexes in acetonitrile solution. Electrochemical and spectroscopic measurements show that the particular electronic characteristics associated with each substituent strongly influence the properties of the resulting FeII complexes as demonstrated by the very intense MLCT transition (∊ 〉 50000 M-1 cm-1) observed in the green complex [Fe(L5)2]2+.

Notizen: Why Pentose-And Not Hexose-Nucleic Acids? Part III. Oligo(2′,3′-dideoxy-β-D-glucopyranosyl)nucleotides. (‘Homo-DNA’): Base-Pairing PropertiesSummary in collaboration with Prof. Dr. C. E. Wintner, Haverford College, Haverford, PA 19041-1392.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.

Notizen: The syntheses of thiazole and fused thiazolo derivatives 2-4, 6-8, 10a-11b, 13-16 from heterocylic isothiocyanates 1, 5, 9, and 12 bearing an ortho ester group and bifunctional reagents, such as substituted propargylamines, is described. Different regioselectivity of intramolecular nucleophilic attack of the thiourea S-atom on the C ≡ C bond, resulting in the formation of both thiazolo and thiazino derivatives, as well as NMR structure elucidation are discussed.

Notizen: An N methylated residue at the n - 3 position of the chain was used to reduce the maximum number of H-bonds realizable y some D,L-alternating oligopeptides in β4.4-, ↑↑5.6- and ↑↓5.6-helices and thus increase for the oligopeptides, the relative stability of larger β-helices. With D, L-alternating oligoleucines of the series Boc-Leun-OMe, however, this approach did not produce the helices expected. Although ↑↓7.2-helices with only one free NH per strand would theoretically be possible, the N-methylated oligoleucines formed instead flawed β4.4-helices having three free NH's in CHCl3 as well as in other solvents of low polarity. These observations confirm that the stability of β-helices does not depend only on the number of intra-or interstrand H-bonds, and corroborate the idea that β-helices with large cavities are inherently unstable.

Notizen: The stabilities of Zn complexes of cysteine and histidine have been determined together with those with those of three derivatives of each n which one of their three donor functions (carboxyl, amino, and mercapto and imidazole, respectively) has been blocked. Using potentionmetric titrations of aqueous solutions, the 1:1 and 1:2 complexes of all for cysteine- and all four histidine-derived ligands are observed among te various species present (ligands, 1:1 and 1:2 complexes, and protonatd derivatives thereof). All cysteine-derived complexes are more stable than the corresponding histidine-derived complexes by 1-2 orders of magnitude for the 1:1 composition and by 1-6 order of magnitude for the 1:2 composition. For the cysteine series, the sequence of stabilities is cysteine 〉 cysteine ethyl ester ≫ N(α)-acetylcysteine ≫ SMethylcysteine. For the histidine series, the corresponding sequence is histidine 〉 histidine methyl ester 〉 N,N (imidazole)-dimethylhistidine 〉 N(α)-acetylhistidine. The order of stabilities can be explained by the relative strengths of the Zn-S vs. Zn-N coordination, y charge effects, and by chelate ring sizes.

Notizen: The stability constants of the Mn2+, Zn2+, Ni2+, pb2+, and Cd2+ complexes with 1,4,7-triazacylononane-1-acetic acid (noma) were determined at 25° and 0.5M (KNO3) by potentiometric titrations. The species [ML] and [ML(OH)] were found in al cases except for Ni2+, whereas [ML2] was only detected for Cd2+. For the complexes [ML], the order of stability is Mn2+ 〈 Cd2+ 〈 pb2+ 〈 Zn2+ 〈 Zn2+ 〈 Ni2+ 〈 Cu 2+, which is consisten with the Irvin-Williams Series.

Notizen: The tetrameric Cu(β-diketonate) alkoxide complex [Cu(thd)(OCH2CH2OCH3)]4 (thd = 2,2,6,6-tetramethyl-3,5-heptanedionate; 1a) reacts with the alkaline earth metal alkoxides [M(OCH2CH2OCH3)2] (M = Ca, 2a; M = Sr, 2b; M = Ba, 2c) to yield the heteronuclear compounds [Cu2M(thd)3(OCH2CH2OCH3)3] (M = Ca, 6a; M = Sr, 6b). These heterometallic complexes were also obtained in the reaction of 1a and the mixed Ca and Sr complexes of β-diketonate-alkoxide [Mx(thd)y(OCH2CH2OCH3)2x-y] (M = Ca, x = 7, y = 6, 3; M = Sr, x = 5, y = 3, 4), respectively. In comparison, 1a reacts with the analogous [Ba(thd)(OCH2CH2OCH3)] (5a) to yield a[Ba2Cu2(thd)4(OCH3)4(HOCH2CH2OCH3)2] species (8a.) The in situ prepared mixed-ligand Ba Compounds [Ba(thd)OR)] (R = CH2CH2OCH2CH2OCH3, (5b); R = CH2CH2CH2OCH3 (5c) react with the corresponding Cu complexes [Cu(thd)(OR)]n (R = CH2CH2OCH2CH2OCH3), n = 4 (1b); R = CH2CH2OCH2CH2OCH3 (8b); R = CH2CH2CH2OCH3 (8c). However, [Cu(hfd)(OCH2CH2OCH3)]4 (hfd = 1,1,1,5,5,5,-hexafluoroacetylacetonate; 1e) is converted in the presence of 2a-c to the simple metathesis products [M(hfd)2] (M = Ca, Sr, Ba) and [Cu(OCH2CH2OCH3)2]. Crystalline [Ba2Cu2(hfd)2(thd)2(OCH2CH2CH2OCH3)4(HOCH2CH2CH2OCH3)2] (9) was isolated from the reaction of 1a with in situ prepared [Ba((hfd)OCH2CH2CH2OCH3)] (5d) in 2-, methoxyethanol. X-Ray crystallographic structure determinations are reported for 6a, 6b, 8b, and 8c.

Notizen: On the Mechanism of Sequential Radical Cyclization of (Bromomethyl)silyl Ethers of Terpernoid AlcoholsThe cyclic products of the Bu3SnH-promoted radical reaction of (E)-1-[(bromomethyl)dimethylsilyloxy]-2-methylhept-2-ene (6) consists to 98% of a 1:2 mixture of (±)-(4RS,5RS)- and (±)-(4-RS,5SR)-4-butyl-2,2,5-trimethyl-1-oxa-2-silacyclohexane (8a and 8b, respectively). It is, therefore, concluded that the 6-‘endo’→5-‘exo’ tandem cyclization of the 5-mehtyl-3-oxa-2-siladeca-5,9-dien-l-yl radical (reaction 1 → 2) is not necessarily a concerted process, but may be explained as a sequence of individual steps via free-radical intermediates.

Notizen: A Mixture of (3S,6R)- and (3R,6R)-3-methyl-6-(1-methylethenyl)dec-9-enyl acetate (1a and 1b, respectively)-1a being a pheromone of the California red scale - is synthesized in 14 steps from (+)-(R)-limonene (4). The key step is the reductive vitamin-B12-catalyzed coupling of (R)-5-(2-iodoethyl)-6-mehtylhept-6-en-2-one ethylene acetal (8) and methyl crotonate (3).

Notizen: A general way for the functionalization of ribonucleosides is described. The method involves the synthesis of the methyl-ribofuranoside derivative 6 equipped with a linker at the 2-hydroxy group (Scheme 2). After introduction of the nucleic-acid bases under standard conditions (Scheme 3), the resulting β-D-ribonucleosides 8 and 10 are further transformed to derivatives with lipophilic, intercalating, and aminoalkyl residues at the linker moiety. In this way, 2′-modified 5-methyluridines 12, adenosines 13, and 5-methylcytidines 15 and 16 were prepared (Scheme 4).

Notizen: Labeling experiments provide evidence that the Fe1- and CO1-mediated losses of H2 and 2 H2 from tetraline are extremely specific in that both reactions follow a clear syn-1,2-elimination involving C(1)/C(2) and C(3)/C(4), respectively. In the course of the multi-step reaction, the metal ions do not move from one side of the π-surface to the other. Independent experiments confirm that the kinetic isotope effect (KIE) associated with the loss of the first H2 molecule is indeed larger than the KIE for the elimination of the second H2 molecule.

Notizen: The highly active immunosuppressive antibiotic rapamycin is a specific inhibitor of a signal transduction pathway that results in exocytosis and transcription. We report the results of the homo- and heteronuclear NMR experiments of rapamycin in DMSO leading to a complete assignment of the 1H- and 13C-NMR signals. With exception of one CH2 group, all diastereotopic assignments could be achieved using heteronuclear long-range coupling constants. Restrained molecular-dynamics simulation in the same solvent as the NMR experiments led to a well defined conformation of the rapamycin molecule in solution. Differences between the solution and crystal structures are discussed.

Notizen: (o-Hydroxyphenyl)methylphosphonic acids are readily obtained from o-(bromomethyl)- or o-(hydroxymethyl)phenols and trialkyl phosphites. Subsequent hydrolysis leads to the corresponding phosphonic acids. For a series of such compounds, the pKa values have been determined by potentiometry. Their dependence on additional substituents in the aromatic ring is discussed in terms of electronic and steric effects.

Notizen: Crystalline N-hydroxyamino-acid derivatives 4, readily available from non-chiral acyl chlorides 2 and sultams 1, were treated with aldehydes in the presence of NaBH3CN to give N-alkylhydroxylamines 5. N,O-Hydrogenolysis of 5 and saponification of 6 furnished (S)-N-alkylamino acids 7 in high optical purity. Similarly, (R)-N-alkylamino acids 12 were obtained from the antipodal acylsultams 8.

Notizen: 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.

Notizen: The cigarette beetle pheromone (-)-serricorole (1) has been synthesized in 23% overall yield by an eight-step sequence starting from N-propionylsultam 3. The synthesis features asymmetric anti- and syn-aldolizations 3 → 4 and 8 → 9, a non-destructive N-acylsultam cleavage with lithiated ethylphenylsulfone (10 → 12), and the smooth, Ti-mediated cyclization of β-acyloxy-ketone 2 to dihydropyranone 14.

Notizen: Synthesis and Pyrolysis of a Triafulvene PrecursorIn view of retro-Diels-Alder reactions (RDA reactions), the triafulvene precursor 3 has been prepared in a simple three-step synthesis by dibromocarbene addition at dibenzo-barrelene (11→12; 44%), halogen-Li exchange followed by methylation (12→14, 100%) and HBr elimination (14→3, 62%) (Scheme 3). Reactivity of the so far unknown bridged 1,1-dibromocyclopropane 12 has been explored, including reductions, allylic rearrangements, and ‘carbene dimerizations’ (Scheme 4). First experiments with respect to the thermal behavior of 3 show that RDA reaction, although occurring in most cases, is not the predominant pathway. When 3 is heated in a sealed tube without solvent, two dimers 26 and 27 are isolated in a total yield of 55% (Scheme 6). On the other hand, gas-phase pyrolysis of 3 at 400° mainly produces rearranged 28 (56%; Scheme 7). It is assumed that bridged trimethylenemethane 29 is an essential intermediate in thermal rearrangements of 3 (Scheme 8).

Notizen: Oxidative treatment of anion 11 (obtained by deprotonation of 6,6-dimethylpentafulvene 10, Scheme 3) with CuCl2 gives a very complex mixture of coupling products 13 (18%), 14 (16%), 15 (36%), 16 (5%), and 17 (6%) (Scheme 4 and Table 2). These results show that the reactive intermediate obtained by oxidation of 11 (which is believed to be the fulvenyl radical 12) has several reactive sites. According to the experiments, reactivity is decreasing in the series C(7) 〉 C(2)/C(3) 〉 C(5) 〉 C(1)/C(4) (Table 2), while simple frontier-orbital considerations would suggest the sequence C(7) 〉 C(5) 〉 C(2)/C(3) 〉 C(1)/C(4). The results suggest that SOMO-SOMO interaction of the approaching fulvenyl radicals 12 is the central effect governing regioselectivity and product distribution, while Coulomb and steric interactions are secondary effects (Table 4).

Notizen: The fluxionality of [Ir4(CO)8(μ2-CO)3L] (L = Br-, I-, SCN-, NO2-, P(4-ClC6H4)3, PPh3, P(4-MeOC6H4)3, P(4-Me2NC6H4)3), as studied by 2D-13C-NMR in solution, is due to two successive scrambling processes: the merry-go-round of six basal CO's and CO bridging to alternative faces of the Ir4 tetrahedron. The basicity of the ligand L has no significant effect on the activation parameters. The scrambling process of lowest activation energy in [Ir4(CO)7(μ2-CO)3(PMePh2)2] correspond to the two possible synchronous CO bridging about a unique face of the metal tetrahedron swapping the relative axial and radial positions of the ligands L. The disubstituted clusters [Ir4(CO)10(μ2-L—L)] with one edge-bridging ligand have a ground-state geometry with three edge-bridging CO's (L—L = bis(diphenylphosphino)methane, bis(diphenylarsino)methane, bis(diphenylphosphino)propane) or with all terminal CO's (L—L = CH3SCH2SCH3). In all cases, the fluxional process of lowest activation energy in the merry-go-round of six CO's about a unique triangular face. For the P and As donor ligands, this process is followed by the rotation of terminal CO's bonded to two Ir-atoms residing on the mirror plane of the unbridged intermediate.

Notizen: Qualitative conformational analysis 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 experimentally investigated so far. In particular, the analysis foresees the existence of a ribopyranosyl isomer of RNA (‘p-RNA’), containing 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 observed in homo-DNA. Experimentally, synthetic β-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 experimental study of the pairing properties of p-RNA, of its potential for constitutional assembly, self-replication, and intra-duplex isomerization to RNA seems mandatory.

Notizen: The molecular structure of a chlorophyll a catabolite isolated from the culture medium of bleached Chlorella protothecoides cells has been determined by X-ray diffraction; the crystal structure shows a distorted helical arrangement of the pyrrole rings and consists of symmetrical dimers located at a crystallographic diad, which are stabilized by six intermolecular H-bonds.

Notizen: 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.

Notizen: 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.

Notizen: The hetero-Diels-Alder addition of SO2 to (E)-hexa-1,3-diene (4) gives first 6-ethyl-3,6-dihydro-1,2-oxathiin 2-oxide (= 6-ethylsultine) with the Et group occupying a pseudoaxial position, and then the more stable stereoisomer 6 with the Et substituent in a pseudoequatorial position. The SO2 additions to 1-methoxybuta-1,3-diene (7) and to 1-methoxy-3-[(trimethylsilyl)oxy]buta-1,3-diene (8) give the 6-methoxysultines 9 and 10, respectively, with the MeO groups in pseudoaxial positions and which do not equilibrate with sultines having pseudoequatorial MeO substituents (anomeric effect). A lower limit of ΔΔG = 3.9 kcal/mol was evaluated at -60° for the stabilizing effect arising from the geminal vicinity of a MeO and sulfinate moiety in 3,6-dihydro-6-methoxy-4-[(trimethylsilyl)oxy]-1,2-oxathiin 2-oxide.

Notizen: UV Irradiation of (Z)- and (E)-1(10)-unsaturated 5,10-secosteroids 1-4 in acetone solution effected, besides (Z/E)-isomerization, (i) a stereospecific epoxidation (only in the presence of O2), which, depending on the configuration ((Z) or (E)) in the starting steroid, gave cis-epoxides 5 and 8 (from the (Z)-compounds 1 and 3) or trans-epoxides 6,9, and 10 (from the (E)-compounds 2 and 4), and (ii) oxidative acetone addition to the olefinic double bond producing 1-acetonyl derivatives 7 and 11a, b.

Notizen: The synthesis of [1,5′-3H2]naltrindole (9) with labels at both the morphine skeleton and the indole moiety was carried out by catalytic tritiodehalogenation of 1,5′-dibromonaltrindole (8) resulting in a specific activity of 46.1 Ci/mmol (1705 GBq/mmol). The brominated precursor was prepared by the Fischer indole synthesis starting from 1-bromonaltrexone (7) and (4-bromophenyl)hydrazine.

Notizen: The three new optically active triamines derived from 2,6-bis(aminomethyl)pyridine, i.e. 2,6-bis{[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]methyl}pyridine (3a), 2,6-bis{[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]methyl}-pyridine (3b), and 2,6-bis{{(2S)-2-[(benzyloxy)methyl]pyrrolidin-1-yl}methyl}pyridine (3c), were synthesized. The equilibrium behaviour in solution and CuII complex formation were studied by acidimetric titration and by UV/VIS and CD measurements. It was found that in aqueous solution, 3a can coordinate one of the CH2OH groups to CuII upon deprotonation. X-Ray crystal structures were determined for the complexes [Cu(3a)Cl]ClO4·H2O, [Cu(3b)Cl]ClO4, and [Cu(3c)Cl]ClO4. In the solid state, coordination of both the OH and the alkoxy groups was observed, and the three ligands are pentacoordinated.

Notizen: Octadienyl carbonates 5 provide cyclic 1,4-dienes 6 when treated with Rh1 complexes (1-10 mol-%) at 80°. Similar cyclization of cyclohexenyl acetate 8 affords cis- fused hexahydroindene 9. Analogous ring closures of nonadienyl carbonate 10 yield preferably the cis-divinypyrrolidine 11 with Rh1 catalysis but the trans-isomer 12 when catalyzed by Pd0. Azaoctadienyl carbonate 5a undergoes elimination with [RhH(PPh3)4] (5 mol-%, 80°) in MeCN giving acyclic triene. 7.

Notizen: Ring-Transformations in the Reaction of 3-(Dimethylamino)-2,2-dimethyl-2H-azirines with 1-Substituted Imidazolidine-2,4,5-trionesReaction of 1-substituted imidazolidine-2,4,5-triones ( = N-substituted parabanic acids; 2) and 3-(dimethylamino)-2,2-dimethyl-2H-azirine (1) in i-PrOH or MeCN at room temperature yields 5,6,7,7a-tetrahydro-3H-imidazo[3,4-a]imidazole-5,7-diones 3 (Scheme 1). By 15N-NMR studies, using (3-15N)-2a, it has been shown that only N(1) in (15N)-3a is labelled and, hence, N(4) stems from 1, e.g. the azirine reacts via cleavage of the N(1)=C(3) bond. In MeCN at room temperature, the azacyclols 3 rearrange slowly to give monocyclic 2H, 5H-imidazol-2-ones 4 (Scheme 3); the 15N-label in (15N)-4a is in position 1. Both reactions proceed via deep-seated skeletal rearrangements, most probably via ring-expansion/ring-contraction processes.

Notizen: Incubation of Spheroplats of Anabaena variabilis (Cyanobacteria) with 22 the 2,6-O-dimetyl-ß-cycoldextrin complex of 2,3-dimethyl-5-phytylhydroquinone (11), revealed the presence of a hitherto unknown enzyme which catalyzes the cyclization of th substrate 11 to give enantiomerically pure γ-tocopherol (3) in ≥ 93% yield.

Notizen: Reaction of 1,3-Thaiazole-5(4H)-thiones and DiazometaneReaction of 4,4-dimethyl-1,3-thiazol-5(4H)-thiones 1 with diazomethane in Et2O at -78° or 0° leads to a mixture of the corresponding 1,4-dithiane 10,1,3-dithiole 11, thiirane 12, 4,5-dihydro-5methylidene-1,3-thiazole 13, and 1,3-thiazol-5(4H)-one 14 (Scheme 3). The structures of 10a, 11a, and 11bhave been established by X-ray crystallography. The formation of the products can be explained via an intermediate thiocaronyl ylide of type E (Scheme 4), generated by the 1.3-dipolar cycloaddition of diazomethane with the exocyclic C=S bond of 1 and elimination of N2. Head-to-head dimerization of E yields 10, 1, 3-dipolar cycloaddition of E and 1 gives the ‘Schönberg product’ 11, and cyclization of E leads to 12, which undergoes a desulfurization to give 13. The thiazolone 141 is formed by hydolysis of E. The similarity of the ratio of the products at -78° and at 0° shows that, in contrast to the reaction of 1 and 2-diazopropane, the elimination of N2 in the primary cycloadduct already occurs at -78°.

Notizen: 3,5,3″,5″-Tetra(tert-butyl)-p-terphenoquinone (12b) was synthesized and characterized by its spectroscopic and X-ray structural data. The ground state of 12b is singlet with a strong contribution of a biradical structure. Paramagnetic derivative of 12b, such as the semiquinone radical anion (12bτ) and its O-protonated form, the phenoxy radical (18), were studied by ESR and ENDOR spectroscopy.

Notizen: A novel type of compound that contains a peptide specific for bacterial peptidoglycans (immunomodulatory activity) and an adamantyl residue (antiviral activity) was synthesized. Thus, L-Ala-D-γGln was linked to DL-Gly(Ada) yielding two diasteroisomers 3a and 3b, i.e. ambo-Gly(Ada)-L-Ala-D-γGln (γGln = isoglutamine-4-amino-4-carbamoylbutanoic acid; Ada = adamantyl). The diastereoisomers were easily separated by column chromatography (silica gel) and characterized, but only the use of a stereospecific enzyme led to the assignment of the configuration of the Gly(Ada) moiety in the two diastereoisomers. The cytotoxic effect and antiviral activity of the novel adamantyltripeptides 3a and 3b, observed as the cell survival and the infectivity reduction of the influenza A virus H1N1 and H3N2 strains, respectively, were studied on MDCK cells in vitro. Both 3a and 3b exhibited low cytotoxicity for MDCK cells and reduced the infectivity of the influenza A virus strains, but to a different extent on different Strain.

Notizen: 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.

Notizen: The diazirine 1, upon thermolysis or photolysis in either acetone or cyclohexanone, at different concentrations, yield the spiro epoxides 2 and 3, and 4 and 5, respectively (Scheme 1). Yield of 2 and 3 depended both on the temperature and the concentration, and correlated inversely with the yield of the major by-product, the enol-derived glycoside 6. Other by-product were the benzyloxglycal7 and the lactone azines 8. ZnCl2-Promoted methanolysis of 2 under mild condition yielded mixture of the uloside 9 and 10 (1.2:1); similarly, 4 yielded 11 and 12 (1.8:1; Scheme 2). More strongly acidic conditions converted 11 into 12, evidencing that ZnCl2-promoted methanolysis proceeds under kinetic control, which is rationalized. The diazirine 13, upon thermolysis of Photolysis in either acetone of cyclohexanone, yielded the α-D-configurated spiro epoxides 14 and 16, and the α-D-configurated dihydrooxazoles 15 and 17, respectively (Scheme 3), which are either formed by ring-opening of ß-D-epoxides, by competitive interception of the initially formed, hypothetical addition products of the intermediate carbene to the ketones. The glycosylidene carbenes, derived from 1 or 13 are not very reactive towards ketones, yields are good only when sterically unhindered ketones are used in large excess.

Notizen: Swern oxidation of 2,3,4,5-tetra-O-benzyl-D-glucose (1) followed by ammonolysis gave the crystalline amide 3 which was oxidized (DMSO/pyridine · SO3) to yield the oxo-amide 4 and the hydroxy-lactams 5 and 6. Cyclization of 4 to the very slowly equilibrating 5 and 6 was completed by treatment with AcOH in CHCl3. The configuration of the hydroxy-lactams was assigned on the basis of NOEs. Reduction (Et3SiH/BF3 · Et2O) of the hydroxy-lactams either individually or as a mixture led to 2,3,4,6-tetra-O-benzyl-D-gluconolactam (7). The procedure, based upon modifications of a patent, does not require chromatography; the overall yield of 7 from 1 is 43%. Hydrogenolysis of 7 gave D-nojirilactam (8); benzylation led to the known pentabenzyl-D-nojirilactam (9) and to the unsaturated lactam 10.

Notizen: The efficient synthesis of all-cis-[5.5.5.5]fenestrane (2) from the readily available intermediate 3 allowed the electron-diffraction analysis of 2. This structure analysis revealed long C—C bonds in the central C(C)4 fragment and a twist-envelope conformation for the four cyclopentane substructures. The four bridgehead H-atoms are in a synclinal rather than an ecliptic position with an approximate D2 symmetry of 2. Planarizing distortions are evident from the opposite bond angles at the central C-atom being 116.2 ± 0.5° with the remaining four being 103.7 ± 0.2°.

Notizen: [Rh1(η5-azulene)(cod)]+BF4- complexes 3a-g (cod = (Z,Z)-cycloocta-1,5-diene) have been synthesized by reaction of [Rh1(cod)]+BF4- in THF with the corresponding azulenes 1a-g (Table 1). The structure of [Rh1(cod)(η5-guaiazulene)]+BF4- (3a) has been determined by X-ray diffraction analysis (Fig. 1 and 2). The Rh-atom is oriented above the five-membered ring of the azulene with almost equal Rh—C distances to all five C-atoms of the ring. The (Z,Z)-cycloocta-1,5-diene ring occurs in two enantiomorphic distorted (C2v → C2) tub conformations in the crystals (Fig. 3). In CDCl3 solution, the cod ligand in the complexes 3 shows a dynamic behavior on the 1H-NMR time scale which is best explained by rotation of the cod ligand relative to the azulene ligands around an imaginary cod—Rh—azulene axis. The new complexes 3 catalyze the formation of heptalene-1,2-dicarboxylates 2 from dimethyl acetylenedicarboxylate (ADM) and the corresponding azulenes 1 just as effectively as [RuH2(PPh3)4] and the analogous [RhH(PPh3)4] complex in MeCN solution (Table 3). On grounds of simplicity, 3 can be generated in situ, when [RhCl(cod)]2 is applied as catalyst (Table 3).

Notizen: In the context of the hypothesis postlating a heterolytic cleavage of a C—N bond during thermolysis of alkoxydiazirines (Scheme 1), we report the preparation of the diazirines 4, 5, 7, and 8, the kinetic parameters for the thermolysis in MeOH of the diazirines 1 and 4-9, and the products of their thermolysis in an aprotic environment. The diazirines 4, 57, and 8 (Scheme 2-5) were prepared from the known hemiacetals 10, 19, 34 (prepared from 31 in an improved way), and 42 according to an established method. The oximes 11, 20, 35, and 43 were obtained from the corresponding hemiacetals as (E/Z)-mixtures; 43 was formed together with the cyclic hydroxylamine 44. Oxidation of 11, 35, and 43 (N-chlorosuccinimide/1,8-diazabicyclo[5.4.0]undec-7-ene (NCS/DBU) or NaIO4) gave good yields of the (Z)-hydroximolactones 12, 36, and 45, while the oxime 20 led to a mixture of the (E)- and (Z)-hydroximolactones 21 and 22, which adopt different conformations. Their configuration was assigned, inter alia, by a comparison with the enol ethers 28 and 29, which were obtained, together with 30, from the reaction of the diazirine 5 with benzaldehyde and PBu3. Treatment of the hydroximolactone O-sulfonates 13, 23, 37, and 46 with NH3/MeOH afforded the diaziridines 15, 25, 38, and 47 in good yields, while the (E)-sulfonate 24 decomposed readily. Oxidation of the diaziridines gave 4, 5, 7, and 8, respectively. Thermolysis of the diazirines 1 and 4-9 in MeOH yielded the anomeric methyl glycosides 50/51, 16/17, 26/27, 52/53, 39/40, 48/49, and 54/55, respectively. A comparison of the kinetic data of the thermolysis at four different temperatures shows the importance of conformational and electronic factors and is compatible with the hypothesis of a heterolytic cleavage of a C—N bond. An early transition state is evidenced by the absence of torsional strain by an annulated 1,3-dioxane ring. Thermolysis of 1 in MeCN at 23° led mostly to the diasteroisomeric (Z,Z)-, (E,E)-, and (E,Z)-lactone azines 56, 57, and 58 (Scheme 6), which convert to 56 under mild conditions, and to 59 (3%). The benzyloxyglucal 59 was obtained in higher yields (18%), together with 44% of 56-58, by thermolysis of solid 1. Similarly, thermolysis at higher temperatures of 4 in toluene, THF, or dioxane and of 9 in CH2Cl2 or THF yielded the (Z,Z)-lactone azines 60 and 61, respectively, the latter being accompanied by the dihydro-oxazole 62.

Notizen: The synthesis of [Ir2Rh2(CO)12] (1) by the literature method gives a mixture 1/[IrRh3(CO)12] which cannot be separated using chromatography. The reaction of [Ir(CO)4]- with 1 mol-equiv. of [Rh(CO)2(THF)2]+ in THF gives pure 1 in 61% yield. Crystals of 1 are highly disordered, unlike those of its derivative [Ir2Rh2(CO)5(μ2-CO)3(norbornadiene)2] which were analysed using X-ray diffraction. The ground-state geometry of 1 in solution has three edge-bridging CO's on the basal IrRh2 face of the metal tetrahedron. Time averaging of CO's takes place above 230 K. The CO site exchange of lowest activation energy is due to one synchronous change of basal face, as shown by 2D- and VT-13C-NMR. Substitution of CO by X- in 1 takes place at a Rh-atom giving [Ir2Rh2(CO)8(μ2-CO)3X]- (X = Br, I). Substitution by bidentate ligands gives [Ir2Rh2(CO)7(μ2-CO)3(η4-L)] (L = norbornadiene, cycloocta-1,5-diene) where the ligand L is chelating a Rh-atom of the basal IrRh2 face. Carbonyl substitution by tridentate ligands gives [Ir2Rh2(CO)6(μ2-CO)3(μ3-L)] (L = 1,3,5-trithiane, tripod) with L capping the triangular basal face of the metal tetrahedron. Carbonyl scrambling is also observed in these substituted derivatives of 1 and is mainly due to the rotation of three terminal CO's about a local C3 axis on the apical Ir-atom.

Notizen: The monosubstituted [Ir4(CO)11L] clusters (L = P(OPh)3, 1; L = P(OMe)3, 2; L = P(OCH2)3CEt, 3) were obtained in good yields by the reaction of [Ir4(CO)11I]- with the corresponding phosphite. In the solid state, cluster 3 has a Cs geometry with all terminal ligands as shown by an X-ray analysis. Three isomers are present in solution: one with terminal ligands (A) and two with three edge-bridging CO's and with L in axial (B) or radial (C) position (see Scheme). The thermodynamic and kinetic parameters of isomerisations B ⇌ A and A ⇌ C were determined by simulation of the variable-temperature 31P-NMR spectra. The three isomers correspond to three minima on the kinetic pathway of CO scrambling, whose relative energies vary independently within a small range (1-9 kJ mol-1 at 298 K). At low temperature, isomer C is always the least stable and is not observed for 1 which bears the most bulky phosphite ligand. The isomerisations are due to two intramolecular merry-go-rounds of CO groups about two unequivalent faces of the unbridged species A.

Notizen: Variable-temperature and -pressure 13C-NMR studies of the 1,3,5-trithiane-capped triruthenium clusters [Ru3(CO)9{μ3-(η3-1,3,5-trithiane)}] (1) and [Ru3(t-BuNC)(CO)8{μ3-(η3-1,3,5-trithiane)}] (2) revealed that CO site exchanges occur via an intramolecular merry-go-round process, involving a transition state mostly dissociative in character.

Notizen: Title compound 1 was synthesized by a published route which had to be modified (seven steps from readily obtainable starting materials). Characterization of 1 was achieved by spectroscopic means (FAB-MS, 1H-NMR, including 2D-COSY). Furthermore, commercially available reference material purchased for comparison, was unequivocally established to be 10, i.e. incompletely deprotected 1.

Notizen: The 2,3-dihydro-1H-benz[f]indole-4,9-diones 3a-d, h were formed in a one-step reaction in 13-82% yield by an unprecedented [3 + 2] regioselective photoaddition of 2-amino-1,4-naphthoquinone (1) with various electronrich alkenes 2 (Scheme 1, Table). The [3 + 2] photoadducts derived from 1 with vinyl ethers and vinyl acetate gave 1H-benz[f]indole-4,9-diones 4e, f, i, in 33-72% yield, by spontaneous loss of the corresponding alcohol or AcOH from the resulting adducts; 4i has a kinamycin skeleton. The [3 + 2] photoaddition also took place on irradiation of the differently substituted amino-1,4-benzoquinones 6, 7, and 12 and excess alkenes 2 in benzene, giving 1H-indole-4,7-dione derivatives 13 and 14 (Scheme 3), 15a and 16 (Scheme 4), and 18 (Scheme 4), respectively. The initial products in these photoadditions were proved to be hydroquinones, the air oxidation of which yielded the heterocyclic quinones; 2,3-dihydro-2-methoxy-2-methyl-5-phenyl-1H-indole-1,4,7-triyl triacetate (19) was isolated after treatment of the crude photoaddition mixture obtained from 2-amino-5-phenyl-1,4-benzoquinone (7) and 2-methoxyprop-1-ene (2f) with Ac2O and pyridine under N2. A pathway leading to the annelated hydroquinones involving ionic intermediates arising from an electron transfer in these photoadditions is proposed (Scheme 5).

Notizen: O-, S-, and N-Nucleophiles are added to the exocyclic double bond of the title compounds 1. The addition of O- or S-nucleophiles yields stable products (Scheme 1), while addition of N-nucleophiles results in thermally labile compounds (Scheme 2). The reaction is studied by spectroscopic methods. From hydrazine adducts, a spiro[azetidine-3,3′-pyrazolidine] 7 is obtained, and the addition products of methyl- and benzylhydrazine rearrange to pyrazol-4-carboxylates 6. Furthermore, the exocyclic double bond is used for the formation of spiro-β-lactams either by cyclopropane formation or by Diels-Alder reactions (Scheme 4). The steric course of all reactions is studied, and it is shown that all reactions with the double bond occur from the side opposite to the bulkier substitutent at C(4) of the β-lactam ring.

Notizen: The radical cation and the radical anion of ‘syn’-cyclobuta[1,2-c:3,4-c′]di-1,6-methano[10]annulene (‘syn’-4a,12a:6a, 10a-bishomobinaphthylene; 3) have been characterized by their hyperfine data. The highly resolved ESR spectrum of \documentclass{article}\pagestyle{empty}\begin{document}$ 3^{+ \atop \dot{}} $\end{document} is dominated by a triplet splitting from the outer pair of methano β-protons (Ho). In contrast, the ESR spectrum of \documentclass{article}\pagestyle{empty}\begin{document}$ 3^{- \atop \dot{}} $\end{document} is poorly resolved with the largest coupling constants arising from perimeter α-protons. The different hyperfine features of \documentclass{article}\pagestyle{empty}\begin{document}$ 3^{+ \atop \dot{}} $\end{document} and \documentclass{article}\pagestyle{empty}\begin{document}$ 3^{- \atop \dot{}} $\end{document} are rationalized by MO models. The SOMO of \documentclass{article}\pagestyle{empty}\begin{document}$ 3^{+ \atop \dot{}} $\end{document} ψSA(b1), has substantial LCAO coefficients of the same sign at the bridged atoms C(1), C(6), C(11), and C(16), whereas in the SOMO of \documentclass{article}\pagestyle{empty}\begin{document}$ 3^{- \atop \dot{}} $\end{document}, ψSS(a1), the four atoms lie in the vertical nodal planes. The large width and the reluctance to saturation of the lines in the ESR spectrum of \documentclass{article}\pagestyle{empty}\begin{document}$ 3^{- \atop \dot{}} $\end{document} are attributed to the near-degeneracy of the lowest antibonding MO's. Due to their similar nodal properties, the SOMO's of \documentclass{article}\pagestyle{empty}\begin{document}$ 3^{- \atop \dot{}} $\end{document} and the radical anions of binaphthylene (4), 1,6-methano[10]annulene (1), and naphthalene (2) are interrelated. Moreover, because the cyclic π-systems in 3 and 1 deviate in the same way from planarity, the effect of such distortions on the coupling constants, aHμ, of the perimeter α-protons in \documentclass{article}\pagestyle{empty}\begin{document}$ 3^{- \atop \dot{}} $\end{document} and \documentclass{article}\pagestyle{empty}\begin{document}$ 1^{- \atop \dot{}} $\end{document} should be comparable. Indeed, on going from \documentclass{article}\pagestyle{empty}\begin{document}$ 4^{- \atop \dot{}} $\end{document} to \documentclass{article}\pagestyle{empty}\begin{document}$ 3^{- \atop \dot{}} $\end{document}, the |aHμ| values are reduced exactaly by half as much as the corresponding values on passing from \documentclass{article}\pagestyle{empty}\begin{document}$ 2^{- \atop \dot{}} $\end{document} to \documentclass{article}\pagestyle{empty}\begin{document}$ 3^{- \atop \dot{}} $\end{document}, of which the cyclic π-systems are twice contained in \documentclass{article}\pagestyle{empty}\begin{document}$ 4^{- \atop \dot{}} $\end{document} and \documentclass{article}\pagestyle{empty}\begin{document}$ 3^{- \atop \dot{}} $\end{document} respectively.

Notizen: The CH2Cl2 extract of the leaves Annona purpurea L. (Annonaceae) showed strong brine shrimp toxicity and pronounced activity against larvae of the yellow-fever mosquito Aedes aegypti. Activity-directed fractionation of the extract by a combination of column chromatography on silica gel, filtration, and high-pressure liquid chromatography led to the isolation of acetogenins 1-6 as the main active principles. The structures of two novel acetogenins named purpureacin 1(5) and purpureacin 2(6) were elucidated by spectroscopic analysis (UV, EI- and DCI-MS, EI-MS of Me3Si derivatives,1H- and 13C-NMR). The configuration of 5 and 6 was not established due to the limited sample amount. Compounds 3-6 also showed antifungal activity against Candida albicans, and 5 was slightly active against Bacillus subtilis.

Notizen: In a theoretical investigation on Ziegler-Natta catalysis, the influence of the coordination number and ligand type of model compounds in relevant reaction steps were studied. Thus, by using the MEHT method, insertion reactions of ethylene into Zr-CH3 and Zr-H bonds were analyzed in systems of the type [Zr(C2H4)R4R′]-[Zr(Cp)(C2H4)R2R′], and [Zr(Cp)(C2H4)R3R′]-(R=R′=CH3, R=CH3, R′=H). It was found that all processes do not have significant kinetic barriers, whereas the reverse reactions in particular the β-hydride elimination have relatively high ones. The influence of coordination geometry and number on these transformations was found to be insignificant. While studying related conversions starting from [Zr(L)(C2H4)R3R′], [Zr(Cp)(C2H4)RR′(L)]+, and [Zr(Cp)(C2H4)R2R′(L)] (L = π-donor, R=R′=CH3 or R=CH3, R′=H) compounds a pronounced π-donor effect was observed. Methyl insertions in these cases showed a higher computed activation barrier than hydride migrations. An orbital basis for this phenomenon was provided and conclusions concerning chain-length control in Ziegler-Natta catalysis were drawn.

Notizen: Four peri-substituted naphthalene-1-diazonium cations all show short attractive interactions between an electron-rich atom of the peri-substituent and the α -N-atom of the diazonium group. These are interpreted as models for incipient nucleophilic attack on a N≡N bond. The diazonium group is a better acceptor of electron density ‘through space’ than the NO2 group, which parallels their relative ‘through-σ-bond’ inductive effects.

Notizen: UV/VIS Absorption spectra of nitrosubsituted (o-hydroxyphenyl)methylphosphonic acids (o-(phosphonomethyl)phenols) were measured as a function of pH at 25° in 0.1M NaClo4 solutions. Computational treatment of the whole set of optical density data between 200 and 500 nm resulted in the determination of the dissociation constants of these polyacids and also of the individual electronic spectra of all the species involved in the deprotonation sequence. The spectral behavior gives information on the structure of the anions formed and consequently the order of the subsequent deprotonation steps could be deduced. For the (2-hydroxy-3-nitro(or 5-nitro)phenyl)methylphosphonic acid and the 2-hydroxy-5-nitro-1,3-phenylenebis(methylphosphonic acid), the phenolic proton dissociates in the last step, while, in the case of (2-hydroxy-3,5-dinitrophenyl)methylphosphonic acid, the last dissociating proton comes from a P—OH group. An intermediate situation is found for (3-chloro-2-hydroxy-5-nitrophenyl)methylphosphonic acid. Generally, the deprotonation sequence is governed by intramolecular H-bonds involving the phenolic OH group.

Notizen: The glycosylation of the 4-methoxypyrazolo[3,4-d]pyrimidine (5) anion with 1-halo-2-deoxyribose 6 in MeCN/TDA-1 gives N2-deoxynucleoside 9 (29%) together with N1-isomer 7 (48%) and its anomer 8 (6%) [7]. The α-D-anomer 8 is not formed and the yield of the ß-D-anomer 7 increased to 62% when dimethoyethane is used as solvent and [18]crown-6 as catalyst. Employing 1-halo-2,3-dideoxyribose 10 instead of halogenose 6, the 2′,3′ -didexoynucleosides 12 and 14 were formed which desilylated (→ 1b and 2b) and converted into the ddI and ddA derivatives 3b (c7z8Idd), 15b (c7z8Add), and 17 (c7z8A′dd). Contrary to 7-deazapurine nucleotides, the triphosphates of 3b and 15b showed on appreciable activity against HIV-reverse transcriptase.

Notizen: Building blocks derived from 7-deazaguanosine (c7G, 1) were prepared for solid-phase oligoribonucleotide synthesis. Compound 1 was converted into the isobutyurl derivative 2b and the (dimethylamino)methylidene compound 3 (Scheme 1). After tritylation (→ 4a, b), silylation was studied with regard to regioselectivity. It was found that the triisopropylsilyl group in combination with the (dimethylamino)methylidene residue gave the highest 2′ -selectivity (→ 5e). The 2′ -O -silyl derivative 5e was reacted with PCl3 affording the 3′ -phosphonate 7 which was used in solid-phase oligoribonucleotide synthesis. Oligonucleotides derived from U-G-G-G-G-U with an increasing number of c7G residues instead of G were synthesized. Aggregation was studied by polyacrylamidegel electrophoresis and CD Spectroscopy. Disaggregation of the G4-structure of U-G-G-G-G-U was observed when c7G replaced G, demonstrating that guanine N(7) participates in the aggregation process.

Notizen: The catalytic hydrogenation of rifamycin S (2) over Pd/C, followed by oxidation with K3[Fe(CN)6], generates a pair of 16,17,18,19-tetrahydrorifamycins S (3/4), epimeric at C(16). The use of PtO2 as catalyst leads to the hydrogenation also of the C(28)=C(29) bond giving, after oxidation by K3[Fe(CN)6], a mixture of the epimers (16R)- and (16S)-16,17,18,19,28,29-hexahydrorifamycins S (5/6). Furthermore, we synthesized the (16R)- and (16S)-3-bromo derivatives 7/8 and (16R)- and (16S)-3-(piperidin-1-yl) derivatives 9/10. The determination of the X-ray crystal structure of the most abundant epimer 4 of the tetrahydrorifamycins allowed the assignment of the absolute configuration at C(16) of all derivative. A Structure-activity relationship study showed that in general the (16R)-epimers are more potent inhibitors of bacterial RNA polymerase than the (16S)-epimers.

Notizen: X-Ray Crystal-structure analysis of 2,4,8,10-tetrakis(1,1-dimethylethyl)-6,6-dimethyl-12H-dibenzo[d,g][1,3,2]-dioxasilocin showed that its eight-membered organosilicon heterocycle adopts a boat-boat (BB) conformation in the solid state (Figs. 2 and 3).

Notizen: Acid-Catalyzed Reactions of 2-Vinylaniline Derivatives with 1-Benzyl- and 1-Methylpiperidin-4-one: An Elegant Synthesis of New Polycyclic Indole DerivativesThe reaction of 2-vinylaniline derivatives with 1-benzylpiperidin-4-one or 1-methylpiperidin-4-one in toluene at temperatures between 115 and 120° with toluene-4-sulfonic acid as catalyst leads in good yields to a new class of polycyclic indole derivatives (Scheme 1, Table 1). The structure of the new diastereoisomerically pure racemic compounds 1-5 is determined by NMR-spectroscopic methods. A reaction mechanism proceeding via cyclization of enamine 9, leading to a racemic, tricyclic reactive intermediate 10, and subsequent intramolecular 1,5-dipolar cyclization as key steps in proposed for the formation of octahydropyrido[4′,3′:4]cyclobut[1,2-b]indoles 1-5. The scope and limitations of the new method are discussed (see Table 2).

Notizen: Five New unusual monoterpene-substituted dihydrochalcones, the adunctins A-E (1″S)-1-{2′-hydroxy-4′-methoxy-6′-[4″-methyl-1″-(1‴-methylethyl)cyclohex-3″ -en-1″ -yloxy]phenyl}-3-phenylpropan-1-one (1), (5aR*,8R*,9aR*)-3-phenyl-1-[5′,8′,9′,9′a-tetrahydro-3′-hydroxy-1′-methoxy-8′-(1″-methylethyl)-5′-a-methyldibenzo-[b,d]furan-4′-yl]propan-1-one (2), (2′R*,4″S*)-1-{6′-hydroxy-4′-methoxy-4″-(1‴-methylethyl)spiro[benzo[b]-furan-2′(3′H),1″ -cyclohex-2″ -en]-7′-yl}-3-phenylpropan-1-one (3), (2′R*,4″R*)-1-{6′-hydroxy-4′-methylethyl-4″-(1‴-methylethyl)spiro[benzo[b]furan-2′(3′H),1″-cyclohex-2″-en]-7′-yl}-3-phenypropan-1-one (4), and (5′aR*,6′S*, 9′R*,9′aS*)-1-[5′a,6′,7′,8′,9′a-hexahydro-3′,6′-methoxy-6′-methyl-9′-(1″-methylethyl)dibenzo[b,d]-furan-4′-yl]-3-phenylpropan-1-one (5) were isolated from the leaves of Piper aduncum (Piperaceae) by preparative liquid chromatography. In addition, (-)-methyllindaretin (6), trans-phytol, and α-tocopherol ( = vitamin E) were also isolated and identified. The structures were elucidated by spectroscopic methods, including 1D- and 2D-NMR spectroscopy as well as single-crystal X-ray diffraction analysis. The antibacterial and cytotoxic potentials of the isolates were also investigated.

Notizen: Geometries of extended structures can be evaluated with the extended-Hückel tight-binding method by inclusion of a distance-dependent weighted Wolfsberg-Helmholz formula and an approximate two-body electrostatic repulsive-energy term. We explain the theoretical procedure which is shown to be straightforward. Application to (all-trans)-polyacetylene yields alternating C, C bond lengths and a bandgap of 1.6 eV at the optimized geometry, in good agreement with the experimental finding.

Notizen: Pd-Catalyzed reaction of 2-(tributylstannyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-indole (5) with a variety of aryl, heteroaryl, vinyl, and allyl halides provides an efficient entry to the corresponding cross-coupled products (see Table).

Notizen: A number of 3-O-substituted 1,3-dihydroxypropan-2-ones have been synthesized in view of their potential use as prochiral precursors of optically active glycerols. Indeed, the oxo-ethers have been reduced to the corresponding 3-O-substituted glycerols via chiral Ru complexes derived from (S)-binap, ( =(-)-(S)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene) with enantiomeric excesses up to 93%. The steric course of the catalytic reduction appears to be essentially dependent on the steric encumbrance of the substituents; indeed, a dramatic increase of the enantiomeric excess is observed when the bulky trityl group is substituted by the less encumbering benzyl or octadecyl groups.

Notizen: A convergent synthesis of the five novel analogues 1a-e of (5′-deoxyadenosin-5′-yl)cobalamin ( = ‘adenosylcobalamin’) is described. The analogues 1a-e carry oligomethylene chains (C3-C7) inserted between the central Co-atom and the 5′-O-atom of the adenosine moiety and are thought to mimick the transition-state geometry in coenzyme-B12-catalyzed rearrangement. All five analogues were characterized by NMR, UV, and FAB mass spectrometry.

Notizen: Experimental results demonstrate that, in the course of gas-phase Fe+-mediated dehydrogenation of tetralin, the metal ion sticks to the same plane of the hydrocarbon surface. The study of 5-substituted, labeled tetralin analogues reveal the operation of an interesting substituent effect: Steric hindrance imposed by a CH3 group at C(5) deflects the metal to the more easily accessible region of C(1)/C(2); in contrast, a CH3O substituent at C(5) directs the metal ion to the more congested C(3)/C(4) region which clearly points to a coordination of Fe+ to the MeO group in the course of the haptotropic migration.

Notizen: The synthesis of 8-azaguanine N9-, N8-, and N7-(2′-deoxyribonucleosides) 1-3, related to 2′-deoxyguanosine (4), is described. Glycosylation of the anion of 5-amino-7-methoxy-3H-1,2,3-triazolo[4,5-d]pyrimidine (5) with 2-deoxy-3,5-di-O-(4-toluoyl)-α-D-erythro-pentofuranosyl chloride (6) afforded the regioisomeric glycosylation products 7a/7b, 8a/8b, and 9 (Scheme 1) which were detoluoylated to give 10a, 10b, 11a, 11b, and 12a. The anomeric configuration as well as the position of glycosylation were determined by combination of UV, 13C-NMR, and 1H-NMR NOE-difference spectroscopy. The 2-amino-8-aza-2′-deoxyadenosine (13), obtained from 7a, was deaminated by adenosine deaminase to yield 8-aza-2′-deoxyguanosine (1), whereas the N7- and N8-regioisomers were no substrates of the enzyme. The N-glycosylic bond of compound 1 (0.1 N HCl) is ca. 10 times more stable than that of 2′-deoxyguanosine (4).

Notizen: Ring Enlargement of Six- to Nine-Membered Heterocycles: Reaction of 3-(Dimethylamino)-2,2-dimethyl-2H-azirine with 3,4-Dihydro-2H-1,2,4-benzothiadiazin-3-one 1,1-DioxidesReaction of 3-(dimethylamino)-2,2-dimethyl-2H-azirine (1) and N-substituted 3,4-dihydro-2H-1,2,4-benzothiadiazin-3-one 1,1-dioxides (4) in CHCl3 yields 3-(dimethylamino)-4,5,6,7-tetrahydro-1,2,5,7-benzothiatriazonin-6-one 1,1-dioxides 5, a novel nine-membered heterocyclic system, by ring enlargement (Schemes 2 and 4). In refluxing MeOH, the heterocycle 5a rearranges to give the N-[1-methyl-1-(1,1-dioxo-4H-1,2,4-benzothiadiazin-3-yl)ethyl]-N′, N′-dimethylurea 10. The three isomeric 2-(methylamino)benzenesufonamides 8,9, and 11 (Scheme 3) are obtained by naBH4 reduction of 5a and 10, respectively. Mechanisms for the thermal isomerization 5a → 10 and the NaBH4 reduction of 5a are proposed in Schemes 5 and 6.

Notizen: Syntheses and Investigations of [Oxazolo[2,3-a]isoindol-9b(2H)-yl]phosphonates and -phosphinates: a New Class of HeterocyclesWe attempted to synthesize diethyl (1-methyl-2-phthalimidoethyl)phosphonate (14a) in a Michaelis-Becker reaction using diethyl sodiophosphonate (13) and the tosylate 12a of (2-hydroxypropyl)phthalimide as starting materials. Instead of TsO substitution in 12a by the nucleophile 13, the carbonyl C-atom of the phthalimido moiety was attacked by 13, followed by an intramolecular nucleophilic substitution at C(2) of the side chain leading to the (oxazolo[2,3-a]isoindolyl)phosphonate 15a (Scheme 1). Similarly, 12a and N-(2-bromoethyl)phthalimide (12b) reacted with butyl (benzene)sodiophosphinate (18) to the (oxazolo[2,3-a]isoindolyl)(phenyl)phosphinates 20a and 20b, respectively (Scheme 2). The attempt to synthesize enantiomerically pure 2-substituted (2-phthalimidoethyl)phosphonates 27 starting from L-α-amino-acids failed, too (Scheme 3): the main products of the reaction of the N,N-phthaloyl-O1-tosyl-L-aminoalcohols 25a-d with 13 were the 3-substituted (oxazolo[2,3-a]isoindolyl)-phosphonates 26a-d, the desired 27b and 27c being observed as by-products in the 31P-NMR spectrum.

Notizen: 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.

Notizen: Double aldols, formally derived from acetic acid and two different aldehydes, as obtained by addition of the enolate of (R,R)-2-(tert-butyl)-6-methyl-1,3-dioxan-4-one (A) to various aldehydes, are reduced to triols which are actually substituted chiral ‘tris(hydroxymethyl)methanes’ (see B and 3-8). Etherifications of the three OH groups of these triols with functionalized halides (allyl, 4-(silyloxy)but-2-en-l-yl, 4-substituted benzyl) and esterifications with pent-4-enoic and 3,5-dinitrobenzyl chlorides, followed by functional group manipulations, lead to the potential center pieces 14-30 for the construction of chiral dendrimers: the building blocks prepared contain the required ‘spacers’ between the core unit, as well as three vinyl groups, three aryl bromide groups, three alcoholic or phenolic OH groups, three mesylate groups, three ester groups, or six arylamino groups at the terminus of their branches. The new compounds are all obtained on a preparative scale and are fully characterized (including elemental analysis).

Notizen: 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.

Notizen: 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.

Notizen: Radical addition to 7-oxabicylco[2.2.1]hept-5-en-2-one (1) was examined from a regiochemical point of view, and despite the small electronic anisotropy of the double bond, electrophilic radicals were found to add preferentially at C(5) with selectivities of up to 5:1. We also report the first case of an inversion of the regioselectivity of a radical reaction using Lewis acids.

Notizen: The asymmetric synthesis of derivatives of the new amino acid (2S)-2-amino-3-(4-hydroxy-3-phosphono-phenyl)propionic acid (3′-phosphono-L-tyrosine; Tyr [3′-PO(OH)2]) is described. The protected amino acid 13 is obtained via a Schöllkopf synthesis by coupling of the rearranged ortho-phosphonophenolic side chain (see Scheme 1, 6a) with the lithiated bis-lactim ether 8 of cyclo(-D-valyl-glycyl-) (see Scheme 2). The incorporation of the protected amino acid 14 in a biologically active dodecapeptide is successfully achieved by the [(9H-fluoren-9-yl)-methoxy]carbonyl (Fmoc) strategy of solid-phase peptide synthesis. Differential protection of Tyr[3′-PO(OH)2] provides four levels of selective deprotection of, in the order, the N2-amino, the carboxyl (cleavage from the resin), the phenol, and the phosphono function (→ peptide 16).

Notizen: Radical addition to enamines using Bu3SnH as reducing agent are reported (Schemes 2 and 4). The diastereoselectivity of these reactions was examined in different systems (Tables 1 and 2). Enamines derived from cyclic ketones such as cyclohexanone were alkylated with high diastereoselectivity with preferential formation of the cis-disubstituted cycloalkanes. In acyclic systems such as enamines derived from propiophenone and diethyl ketone, moderate to high stereoselectivities were observed in the H-abstraction step. A model based principally on minimization of allylic 1,3-strain (A1,3 strain) was deduced from the experimental results and semi-empirical (AM1) calculations.

Notizen: 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 C—C and the C—N 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.

Notizen: Starting from iodoalcohol 9, the monoprotected dialdehyde 5 was synthesized (Scheme 2) and converted to 17 by reaction with oxo-phosphonate 15 (Scheme 3). The latter was prepared from 13. Cyclisation of 17 to the target compound 18 failed. Also the attachment of thiol 22 to lactone 19 was unsatisfactory (Scheme 4). Therefore, the building blocks 28 and 29 were synthesized using diene 33 and diester 30 as starting material for 28 and 9 for 29 (Scheme 5 and 6). Hydroxy acid 28 was converted into formyl-ester 46 (Scheme 7). However, the condensation of its derivatives 48 and 49 with ‘Umpolung’ of the carbonyl reactivity was unsuccessful, probably due to steric hindrance.

Notizen: A versatile process for the preparation of a number of 3-thio-substituted furans 1-4 is described. These products have very low odor thresholds and are thus potent flavor compounds. Fur-3-yl thiocyanates 10a, b as well as other S-containing analogues (2b, 7a, b, and 8) were prepared by a Michael-type addition of thiocyanic acid, thioacetic acid, alakanethiols, and sodium thiosulfate to alkynones 6 or 15, followed by cyclization (Schemes 3 and 4). The thiocyanates 10a, b were converted to mixed disulfides 3, symmetric disulfides 4, thioethers 2, and thiols 1, using ‘hard’ or ‘soft’ nucleophiles or reducing agents, respectively (Scheme 6).

Notizen: For the alkaloid raumacline (2), which is a biotransformation product of ajmaline (1) in Rauwolfia serpentina cell cultures, an efficient ‘one-pot’ synthesis was developed using a NaBH4/riboflavin/light-mediated transformation of 1 into 2 with a total yield of 86%.

Notizen: The known triterpenoids β-amyrin (= olean-12-en-3β-ol; 22), lupeol (= lup-20(29)-en-3β-ol; 17), betulin (= lup-20(29)-ene-3β,28-diol; 18), lup-20(29)-ene-3β,30-diol (20), oleanolic acid (= 3β-hydroxyolean-12-en-28-oic acid; 21), and betulonic acid (= 3-oxolup-20(29)-en-28-oic acid; 19), together with epicatechol (= cis-2-(3,4-dihydroxyphenyl)-3,4-dihydro-2H-1-benzopyran-3,5,7-triol; 23), 5′-O-methylgallocatechol (= trans-2-(3,4-dihydroxy-5-methoxyphenyl)-3,4-dihydro-2H-1-benzopyran-3,5,7-triol; 24), and 4-hydroxybenzaldehyde were isolated from the aerial parts of Maytenus boaria (MOL.). Additonally, the eight 4,C4-dihydro-β-agarofuran sesquiterpenoids 1-8, one of them a diol with a (4R)-configuration, and compound 9 were present in the extract. The structures of these compounds were established by spectroscopic and chemical means.

Notizen: Diasteroisomeric secouridine derivatives, appropriately protected and activated, served as starting compounds in the reactions with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in various solvents (CH2Cl2, MeCN, or dimethylformamide (DMF)). Reactions with DBU/CH2Cl2 gave N(3)-methylene-bridged bis-secouridines and bis-uridines (Scheme 3), while the reactions with DBU in non-alkylating solvents resulted in formation of secdinucleosides as the result of intermolecular ‘dimerizations’ (Scheme 2).

Notizen: Farnesol (3a) is the precursor to the irregular C12 terpenoid (4S, 4aS, 8aS)-1,2,3,4,4a,5,8,8a-octahydro-4,8a-dimethylnaphthalen-4a-ol (= dehydrogeosmin; 1). The irregular C-backbone originates from the oxidative removal of a C3 side chain from a C15 eudesmane-type intermediate (Scheme 2). The bicyclic C-framework is assembled by a formal addition of H2O across the endocyclic double bonds of a monocyclic germacradiene-type precursor. The biosynthetic pathway follows from administration of the deuteriated farnesols 3b-e to flower heads of the cactaceae Rebutia marsoneri Werd. and mass-spectroscopic analysis of the collected volatiles.

Notizen: A new open-chain monoterpene glycoside, anatolioside E (1), was isolated from the leaves of Viburnum orientale in addition to three known acyclic monoterpene glycosides, betulalbusides A (2) and B (3), and 2(E)-2,6-dimethyl-2,7-octadien-1,6-diol-6-O-β-D-glucopyranoside(4). The structure of anatolioside E (1) was elucidated on the basis of chemical and spectral data as 6-O-[β-D-glucopyransoyl-(1‴‴ → 6‴″)-2-(E), 6(R), 2,6-dimethyl-6-hydroxy-2,7-octadienoyl-(1‴″ → 2″″)-β-D-glucopyranosyl-(1″″ → 6‴)-2-(E), 6(R), 2,6-dimethyl-6-hydroxy-2,7-octadienoyl-(1‴ → 4″)-α-L-rhamnopyranosyl-(1″″ → 2′)-β-D-glucopyranosyl]linalool.

Notizen: Several oligomeric derivatives 1-5 of (R)-3-hydroxybutanoic acid and a cyclic trimer of (R)-3-hydroxypentanoic acid (6) were used as ionophores to transport potassium picrate across a bulk liquid CH2Cl2 membrane. Using the cyclic trimer 1 and an oligomer mixture of (R)-3-hydroxybutanoic acid, 5 (ca. 28-mer), for the transport experiments, the alkali-metal ions from Li+ to Cs+ and the alkaline-earth-metal ions from Mg2+ to Ba2+ were also shown to be transported through the organic phase. Although a pronounced enhancement of the transport rates was observed in the presence of 3-hydroxyalkanoate oligomers, no special selectivity for one ion was detected. The ionophore properties of the investigated oligomers and oligolides derived from 3-hydroxybutanoic acid are compatible with the alleged role of oligo(3-hydroxybutanoate) (c-PHB; ca. 120-mer) as component of ion channels through cell membranes.

Notizen: 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.

Notizen: 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 C=C 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).

Notizen: The triolide of (R)-3-hydroxybutanoic acid ((R,R,R,))-3,7,11-trimethyl-2,6,10-trioxadodecane-1,5,9-trione; (1), readily available from the corresponding biopolymer P(3-HB) in one step, forms crystalline complexes with alkali and alkaline earth salts. The X-ray crystal structures of three such complexes, (3 NaSCN)·4 1 (2), (2 KSCN)·2 1 · H2O (3), and (2) Ba(SCN)2 · 2 1 · 2 H2O · THF (4), have been determined and are compared. The triolide is found in these structures (i) as a free molecule, making no contacts with a cation (clathrate-type inclusion), (ii) as a monodentate ligand coordinated to a single ion with one carbonyl O-atom only, (iii) as a chelator, forming an eight-membered ring, with two carbonyl O-atoms attached to the same ion, (iv) as a linker, using two carbonyl O-atoms to bind to the two metals of an ion-X-ion unit (ten-membered ring), and (v), in a crown-ester complex, in which an ion is sitting on the three unidirectional C=O groups of a triolide molecule (Figs. 1-3). The crystal packing is such that there are columns along certain axes in the centers of which the cations are surrounded by counterions and triolide molecules, with the non-polar parts of 1 on the outside (Fig. 4). In the complexes 2-4, the triolide assumes conformations which are slightly distorted, with the carbonyl O-atoms moved closer together, as compared to the ‘free’ triolide 1 (Fig. 5). These observed features are compatible with the view that oligo (3-HB) may be involved in the formation of Ca polyphosphate ion channels through cell membranes. A comparison is also made between the triolide structure in 1-4 and in enterobactin, a super Fe chelator (Fig. 5). To better understand the binding between the Na ion and the triolide carbonyl O-atoms in the crown-ester complex, we have applied electron-localization function (ELF) calculations with the data set of structure 2, and we have produced ELF representations of ethane, ethene, and methyl acetate (Figs. 6-9). It turns out that this theoretical method leads to electron-localization patterns which are in astounding agreement with qualitative bonding models of organic chemists, such as the ‘double bond character of the CO—OR single bond’ or the ‘hyperconjugative n → σ* interactions between lone pairs on the O-atoms and neighbouring σ-bonds’ in ester groups (Fig. 8). The noncovalent, dipole/pole-type character of bonding between Na+ and the triolide carbonyl O-atoms in the crown-ester complex (the Na—O=C plane is roughly perpendicular to the O—C=O plane) is confirmed by the ELF calculation; other bonding features such as the C≡N bond in the NaSCN complex 2 are also included in the discussion (Fig. 9).

Notizen: Macrocycle 3 with a hydrophobic cavity and an appended thiazolium ring is prepared following a novel synthetic sequence to monofunctionalized cyclophanes. Although the thiazolium ring of 3 prefers to be located in the cyclophane cavity, it could be displaced with low energetic costs by benzene and naphthalene guests which form stable 1:1 inclusion complexes with 3 in protic solvents. Initial rate studies show that 3 is a pyruvate-oxidase mimic and catalyzes the oxidation of aromatic aldehydes to carboxylic acids in aqueous solution. Cyclophane 3 also catalyzes the conversion of aromatic aldehydes to the corresponding esters in alcoholic solvents. The supramolecular catalyst 3 exhibits enzyme-like saturation kinetics, large turnover numbers, as well as high reaction and substrate selectivity, and it is far superior to the non-macrocyclic catalysts 4 and 5 which lack a substrate binding site. Following cyclic voltammetric investigations of the redox behavior and stability of thiazolium ions, a new one-pot electrochemical synthesis of aromatic esters is developed: Aromatic esters are prepared efficiently by indirect electrochemical oxidation of the corresponding aldehydes in alcoholic solvents, mediated by two coenzymes, the thiazolium ions 3 or 5 and flavin 21. At the extraordinarily low working electrode potential of -300 mV (vs. Ag/AgCl), high yields of the esters are obtained with high current efficiencies and high turnovers of the catalysts which are stable under the reaction conditions. The origin of the substrate and reaction selectivity, which is particularly pronounced in the supramolecular reactions catalyzed by 3, is analyzed.