ALBERT

Notizen: -The solid-phase synthesis and characterization of a series of peptides (3-9), containing reverse-turn mimetic bicyclic lactams (1a, 1b), was reported in the preceding paper. The bicyclic lactams (1a, 1b) possess high structural similarity to the two central residues of a β-turn. The conformational preferences of the constrained peptides have been investigated by NMR spectroscopy and IR spectroscopy. Our experimental results have been complemented by computer modelling studies and show that the constrained peptides (3-9) form an inverse γ-turn or a type-II′ β-turn through intramolecular hydrogen bonding, depending on the nature of the reverse-turn mimic. In N-acetylated tetrapeptide mimics incorporating the two different bicyclic lactams (a series and b series), H5 is available for either a γ-turn (7-membered ring with the carbonyl group of the bicyclic lactam) or a β-turn (10-membered ring with the carbonyl group of residue 2), as shown in Figures 7 and 9. The a series incorporating the (5,7)-bicyclic lactam predominantly induces the γ-turn conformation, while the b series incorporating the (5,6)-bicyclic lactam can promote either a γ-turn or a β-turn conformation, with the β-turn usually being preferred and with varying degrees of β-hairpin formation.

Notizen: -The computer program COCON is introduced as a tool for the comprehensive structure elucidation of unknown organic compounds. In particular, structural proposals made on the basis of the molecular formula and of 2D-NMR experiments can be analyzed for the existence of alternative constitutions being in agreement with the same data set. The computational speed grounds on the evaluation of ambiguous long-range connectivity information during the process of structure generation. The data set experimentally obtained for the marine natural product oroidin (1) was selected, because proton-poor compounds usually cause uncertainties in NMR-based structure determinations. The calculation results encourage to move from the experience-based analysis of NMR chemical shifts or of MS fragmentations to the automated evaluation of routinely available connectivity information.Supporting information for this article is available on the WWW under -http://www.wileY-Vch.de/contents/jc_2046/1999/98241_s.pdf or from the author.

Notizen: The dioximes 4-6 and the dimethoximes 7-9, which contain the functional groups in opposite positions of a six-, eight-, or ten-membered ring, were synthesized. Their conformational properties and transannular interactions were investigated by spectroscopic (PE, 13C NMR) and theoretical (MMX, AM1, ab initio HF, and B3LYP) methods. While the cyclooctane derivatives 5 and 8 have conformations favourable for through-space interactions of the π(C=N) orbitals, in the other compounds no such interactions can be ascertained. Through-space orbital interactions in the molecules with an eight-membered ring lead to a splitting of the π(C=N) MOs of 0.4 eV.

Notizen: The bicyclic dioximes 4-6 and dimethoximes 7-9, which contain the functional groups in opposite positions of bridged eight-membered rings, were synthesized. Their conformational properties and transannular interactions were investigated by spectroscopic (PE, 13C NMR) and theoretical (MMX, AM1, ab initio HF, and B3LYP) methods. While in the 3,7-disubstituted bicyclo[3.3.1]nonane derivatives 5 and 8 the eight-membered ring has a CC conformation favourable for through-space interactions of the π(C=N) orbitals, in the bicyclo[3.3.0]octane derivatives 4 and 7 as well as the 2,6-disubstituted bicyclo[3.3.1]nonanes 6 and 9 the functional groups are in geometric orientations that are unfavourable for such interactions. Through-space orbital interactions in the molecules with favourable conformations lead to a splitting of the π(C=N) MOs of 0.4-0.6 eV.

Notizen: A series of compounds Q2Z was prepared, where Q = [2.2]paracyclophan-4-yl and Z = C(=O) (4), CH2 (5), SiMe2 (6), S (7), P(=O)OMe (8), and C(=O)C(=O) (9). Because of the planar chirality of Q, these compounds occur as meso- (m) and chiral (c) diastereomers, which were formed in equal amounts. They were separated in the cases of 4-7 and enriched in the case of 9 (diastereomeric ratio ca. 7:3). Compound 8 possesses a pseudoasymmetric phosphorus centre and occurs as one chiral (8c) and two meso diastereomers (8m1, 8m2), all three of which were isolated separately. The configurations of 5m/5c, 6m/6c, and 8c were directly determined by NMR spectroscopy, that of 4m/4c indirectly by reducing the separated compounds to 5m and 5c, respectively, and that of 7m by X-ray diffraction. The favoured conformations of 4-8 were studied by molecular mechanics computations by using the MM3(94) program. An attempt was made to rationalize some chemical shift differences between diastereomers on the basis of the conformers predicted.

Notizen: The proton-transfer equilibrium of several bases and acids, including some sterically hindered ketones, sulfoxides, and phenols, has been investigated by means of the determination of the thermodynamics of the equilibrium, NMR 13C relaxation measurements, and quantum chemical calculations. The analysis of such data yields information about the steric effects on basicity or acidity and about the underlying reasons for the anomalous behavior of species having a sterically hindered basic or acidic site. Thus, it is demonstrated that the anomalously low basicity of two sterically hindered ketones (tBu2CO and PhCOtBu) is enthalpic in origin and stems from steric hindrance to the solvation of their protonated forms. No such effect is found for analogous sulfoxides, whereas phenols display a more complex behavior.Supporting information for this article is available on the WWW under //http://www.wiley-vch.de/contents/jc_2046/1999/99105_s.pdf or from the author.

Notizen: (±)-γ-Lycorane has been synthesized in ten steps from piperonylic alcohol. Two radical reactions were used successively to build the D and B rings. A formal synthesis of (+)-γ-lycorane was achieved via an optically active unsaturated aldehyde intermediate.

Notizen: This paper describes an efficient stereocontrolled and convergent approach towards the C1-C13 polyol fragment of amphotericin B. The strategy is based on the stereoselective reduction of a chiral β,γ-dioxo-ε-sulfinyl ester to obtain anti- or syn-1,3-diols.

Notizen: The physicochemical characterization of MS-325 [trisodium {4-(R)-[(4,4-diphenylcyclohexyl)phosphanooxymethyl]-3,6,9-triaza-3,6,9-tris(methoxycarbonyl)undecanedioato}gadolinium(III)], a new derivative of Gd-DTPA {Magnevist®: dimeglumin [{3,6,9-triaza3,6,9-tris(methoxycarbonyl)undecanedioato}gadolinium(III)], presented as a potentially useful angiographic contrast agent, was carried out in various media. Water solution, protein-containing solution, phosphorylated metabolites solution, and Zn2+-containing solution were investigated using different NMR techniques such as water 1H nuclear magnetic relaxation rates, water 17O transverse relaxation rates, and 31P longitudinal relaxation rates of phosphorylated metabolites. The proton relaxivity of MS-325 in water was found to be higher than that of the parent compound Gd-DTPA; this can be attributed to the longer rotational correlation time (τR) of the hydrated complex, and possibly to an apparently shorter mean distance (r) between the protons of the coordinated water molecule and the gadolinium ion. The kinetic and thermodynamic stability of MS-325 in solutions containing phosphorylated metabolites (ATP, phosphocreatine and inorganic phosphate) were measured by 31P relaxation rate analysis and found to be higher than for Gd-DTPA. Similarly, the Zn2+ transmetallation process studied by proton relaxometry is slower than for the same reference compound. Finally, an analysis of the noncovalent binding of MS-325 to serum proteins by proton relaxometry showed that MS-325 interacts with human serum albumin (HSA) and that the association constant of this interaction is equal to 6100 ± 2130 M-1. A peak relaxivity of approx. 50 s-1mM-1 was determined at 25 MHz for the protein-bound paramagnetic complex. This value is lower than the maximal relaxivity predicted for a paramagnetic center totally immobilized at the surface of the protein.

Notizen: A two-step synthetic approach to penta- and hexahelicenes substituted at the terminal aromatic rings has been studied. This approach is based on the Diels-Alder reaction of 5,5′,8,8′-tetramethyl-3,3′,4,4′-tetrahydro-[1,1′]-binaphthalene (2b), 3-vinyl-1,2-dihydronaphthalene (5a), 5,8-dimethyl-3-vinyl-1,2-dihydronaphthalene (5b) and 3-vinyl-1,2-dihydrophenanthrene (15) followed by the aromatization of the cycloadducts. This method is flexible, efficient and of wide application to the synthesis of several benzenoid and nonbenzenoid penta- and hexahelicenes. The racemization energy barriers of helicenes 3, 9, 10, 13, 14, 17 and 18 were computed with the semiempirical quantum method AM1. The computed values show that, when methyl groups are introduced at the inner position of the terminal aromatic rings, the racemization barriers increase markedly. A structure analysis of the reaction products by 1H- and 13C-NMR spectroscopy is also presented.

Notizen: -The site of deprotonation of several types of amide acids (carboxylic amides and imides, sulfonamides, cyanamide, N-hydroxyurea) has been investigated by quantum chemical calculations and heteronuclear NMR measurements. Relative energies of tautomeric ions deriving from protonation at the various sites were determined both in the gas phase and in water (by the IPCM continuum solvation method). NMR properties (nuclear shielding and electric field gradient) of the involved heteronuclei were calculated and compared with experimental 14N, 17O and 33S chemical shifts and relaxation rates. It is shown that the combination of theoretical and experimental tools allows a reliable prediction of spectral parameters and ultimately of the deprotonation site of polyfunctional acids.Supporting information for this article is available on the WWW under -http://www.wileY-Vch.de/contents/jc_2046/1999/98401_s.pdf or from the author.

Notizen: Metalation of triisopropylsilylphosphane with bis(tetrahydrofuran-O)calcium bis[bis(trimethylsilyl)amide] in tetrahydropyran (thp) in a molar ratio of 3:2 yields (Me3Si)2NCa[μ-P(H)SiiPr3]3Ca(thp)3 (1) containing a trigonal-bipyramidal Ca2P3 core, the metal atoms occupying apical positions. Reaction of two equivalents of triisopropylsilylphosphane or -arsane with bis(tetrahydrofuran-O)barium bis[bis(trimethylsilyl)amide] in tetrahydrofuran gives the corresponding bis(phosphanide) 2 and bis(arsanide) 3, compounds of the type (thf)3Ba[μ-E(H)SiiPr3]Ba(thf)2E(H)SiiPr3 with E = P, As. The equimolar reaction of (tri-tert-butylsilyl)phosphane with (thf)2Ba[N(SiMe3)2]2 in toluene yields heteroleptic dimeric (thf)2Ba[N(SiMe3)2][P(H)SitBu3] (4). Addition of a further equivalent of H2PSitBu3 leads to the formation of homoleptic (thf)nBa[P(H)SitBu3]2 (5). Dissolution of the latter in aromatic hydrocarbons leads to the elimination of H2PSitBu3, yielding dimeric (thf)Ba3(PSitBu3)2[P(H)SitBu3]2 (6). The inner core of 6 consists of the tetramer (BaPSitBu3)4 based on a Ba4P4 heterocubane unit, two opposite faces being capped with (thf)Ba[P(H)SitBu3]2 molecules.

Notizen: A new thiocyanatomolybdenum(VI) dioxo-μ-oxo complex dimer bearing a 4,4′-di-tert-butyl-2,2′-bipyridine ligand (2) is shown to exist in the crystal cell unit as a meso (Mo-O-Mo angle of 180°) and d,l, pair (Mo-O-Mo angle of 155.7°). These conformers are in equilibrium in solution and have been observed clearly by 1H NMR spectroscopy.

Notizen: The 1,1′-bis(chlorostannyl)-substituted ferrocenes Fe(C5H4-SnMe2Cl)2 (2), Fe(C5H4-SnMeCl2)2 (3) and Fe(C5H4-SnCl3)2 (4) were prepared, starting from 1,1′-bis(trimethylstannyl)ferrocene (1). Treatment of the chlorides with Li[AlH4] afforded the 1,1′-bis(hydridostannyl)-subsituted ferrocenes Fe(C5H4-SnMe2H)2 (5), Fe(C5H4-SnMeH2)2 (6) and Fe(C5H4-SnH3)2 (7), respectively. All complexes 1-7 were studied by 1H-, 13C-, and 119Sn-NMR spectroscopy with 1D and 2D techniques. The compounds 1-4 were investigated by temperature-dependent 119Sn- and 57Fe-Mössbauer spectroscopy. The electrochemistry of 1-5 gave evidence of reversible one-electron oxidation processes. The molecular structure of 1,1′-bis(trichlorostannyl)ferrocene (4) was determined by X-ray structural analysis, and there was no indication of intra- or intermolecular Sn···Cl···Sn interactions. This direct structural information proved to be consistent with both the Mössbauer and the solution NMR spectroscopic data.

Notizen: The reactions of [N3P3(dobp)2Cl2] and [N3P3(dobp)Cl4] with a mixture of HOC5H4N-4 and K2CO3 in acetone give the cyclotriphosphazenes [N3P3(dobp)2(OC5H4N-4)2] and [N3P3(dobp)(OC5H4N-4)4], respectively. These compounds react with [W(MeOH)(CO)5] in methanol to give mixtures of the polymetallic complexes [N3P3(dobp)2(OC5H4N-4)2{W(CO)5}x] (x = 1, 2) and [N3P3(dobp)(OC5H4N-4)4{W(CO)5}x] (x = 1-4), which are unstable in solution, slowly undergoing loss of the pentacarbonyl moiety. A complete characterization by multinuclear 1H, 15N, 31P, 183W magnetic resonance has revealed that the complexation of the N atom of one 4-oxypyridine ligand by the W(CO)5 fragment has a measurable effect on other parts of the phosphazene molecule very far away from the coordination site. The changes observed in δ183W have been used to identify the components in mixtures of compounds incorporating different numbers of tungsten atoms in the molecule. The characterization of less sensitive nuclei has been accomplished by means of indirect detection methods.

Notizen: Bis(phosphonio)benzo[c]phospholides (isophosphindolides) 1a,b have been found to react with magnesium or alkali metal naphthalenides MC10H8 (M = Li, Na, K) with reduction of one or both of the phosphonio groups. The main products are the mono- or bis(phosphanyl)-substituted heterocycles 2, 3, 6, 7, which have been characterized by in situ NMR studies and in some cases isolated. Subsequent reaction of 2 with excess [Ni(CO)4] gave the complex 4, which has been characterized by X-ray diffractometry. Reactions of 1a with alkali metals followed a more complicated course and gave a mixture of 2, 3, and the substitution product 8, which was further reduced to the phosphanido-substituted benzo[c]phospholide 9. The latter could be formed selectively by first converting 1a into 8 by treatment with PhNa and then treating this with lithium. NMR data of the phosphane-substituted benzo[c]phospholides and the structural features of 4 are discussed.

Notizen: -The application of the new computer program COCON (Constitutions from Connectivities) to the 2D-NMR data sets of three different complex natural products is described. The investigated compounds are proton-poor and therefore underdetermined systems. For such molecules the number of possible constitutions and the computational speed of COCON are of interest. Our investigation is focused on how methods of 13C-NMR chemical shift prediction can assist chemists with regard to refining the selection among the constitutions proposed by COCON.

Notizen: -rac-(E)-Opposita-4(15),7(11)-dien-12-al (1) was synthesized in 12 steps via the aldehyde 11 as the key compound. The spectroscopic data of rac-1 are identical with those of the corresponding natural product, previously isolated from Vetiver oil. Synthetic rac-1 has a strong, green woody odor with soft-floral undertones, which confirms that 1 is an olfactorily important constituent of Vetiver oil.

Notizen: -Seven new cytotoxic dimeric steroids, namely crellastatins B-H (2-8), have been isolated from the Vanuatu sponge Crella sp. They have been structurally characterized on the basis of 2D-NMR (500 MHz) and FAB-MS data. All the new compounds show the same unprecedented junction between the monomeric units, formed via their side-chains, whereas they differ from A (1) in the hydroxylation pattern of the two tetracyclic cores. Like crellastatin A (1), crellastatins B-H (2-8) exhibit in vitro antitumor activity against human bronchopulmonary non-small-cell lung carcinoma cell lines (NSCLC) with IC50 values in the range of 2-10 μg/mL.

Notizen: -Fruit bodies of the wood-rotting North American fungus Hapalopilusmutans produce a mixture of dihydroxybenzoic acids 1, dihydroxybenzoquinones 2 and a novel type of spirodiones, e.g. mutadione A (4a). All compounds carry long alkyl chains, which may be partially unsaturated. The structures of the metabolites were established by spectroscopic methods.

Notizen: The natural products pyrenophorin (1a) and citronellol (2a), in which CH3 groups are replaced by CF3, were synthesized in enantiomerically pure form from simple four-carbon trifluorohydroxy acids (obtained by resolution). The cyclizations of analogous CH3 and CF3 seco acids (cf. 9) to give pyrenophorin derivatives require different methodologies; the F6 derivative 10a could be obtained in only very poor yield; in contrast to pyrenophorin. Most surprisingly, F6-pyrenophorin (1d) has an extremely poor solubility in common organic solvents, and has essentially no antimicrobial activity (see Table 2). The synthesis of F3-citronellol is the first application of an enantiopure F3-Roche acid (12) as a synthetic builiding block (see its derivatives 17-23). An olfactory comparison of F3-citronellol [(R)-(+)-2b] with citronellol and ent-citronellol (Scheme 6) shows that the fluorine derivative has a “very metallic, aggressive” character and lacks totally the “sweetness” of (R)-(+)- and (S)-(-)-2a. A number of generally useful, CF3-substituted electrophilic (iodides 4, 18, 37, tosylates 19, 33, aldehydes 5, 29, 39) and nucleophilic (Li dithiane precursor of 5, Li compounds 20, 38) reagents are described for the first time.Supporting information for this article is available on the WWW under //http://www.wiley-vch.de/contents/jc_2046/1999/99137_s.pdf or from the author.

Notizen: The sponge-derived fungi Ulocladium botrytis and Asteromyces cruciatus, and the algal-derived fungus Varicosporina ramulosa, were isolated and extracts from cultures investigated for their metabolite production. Investigations of the extract of the culture of U. botrytis guided by bioassay yielded the new tyrosine kinase (p56lck) inhibitor ulocladol (1) together with 1-hydroxy-6-methyl-8-(hydroxymethyl)xanthone (3), which showed antifungal activity. The extract of the culture medium of A. cruciatus yielded the new metabolite (+)-2,4-dimethyl-4,5-dihydrofuran-3-carbaldehyde (4) together with the known compounds (3S,5R)-dimethyldihydrofuran-2-one (5) and tri-O-acetyl glycerol. From V. ramulosa the five macrodiolides grahamimycin A1 (6), colletoketol (7), (6R,11R,12R,14R)-colletodiol (8), 9,10-dihydro-(6R,11S,12S,14R)-colletodiol (9) and 9,10-dihydro-(6R,11R,12R,14R)-colletodiol (10) together with ergosterol were obtained, 9 and 10 being new fungal metabolites.

Notizen: A ganglioside molecular species SJG-1 has been obtained from the n-hexane soluble lipid fraction of the chloroform/methanol extract of the sea cucumber Stichopus japonicus. On the basis of chemical and spectroscopic evidence, the structure of SJG-1 has been determined. SJG-1 possesses an N-glycolylneuraminic acid (sialic acid), nonhydroxy fatty acids and phytosphingosine-type long-chain bases as major ceramide components. The ganglioside SJG-1 exhibits neuritogenic activity toward the rat pheochromocytoma cell line PC12 cells in the presence of NGF.

Notizen: A versatile method for the preparation of indolizidine alkaloids from 1-benzyloxy-5-(p-toluenesulfonamido)-3-alken-2-ols as stereodefined key intermediates has been developed. The utility of this approach was demonstrated by the synthesis of (+)-monomorine I.

Notizen: Synthetic protocols for the manipulation of the polyhydroxylated southern region of ingenol (1a) were developed, and a series of isosteres of the anticancer compound ingenol 3,20-dibenzoate (1b) was prepared. The biological evaluation of these compounds showed that cytotoxicity was relatively tolerant to changes at C-20, while PKC activation was markedly affected by these modifications. These data suggest that chemical manipulation can effectively dissect cytotoxicity and tumour-promoting activity (or potential) of ingenoids, affording more optimal candidates for development, like 20-deoxy-20-fluoroingenol 3,20-dibenzoate (5b). In mild acidic medium, an unexpected vinylogous retro-pinacol rearrangement of ingenol to a tigliane derivative was observed.

Notizen: A conformational study is reported on 2′-deoxyguanosine 5′-methylmonophosphate [MepdG (1)] and 2′-deoxyguanosine 3′-methylmonophosphate [dGpMe (2)] and their interactions with Mg2+, Zn2+ and Hg2+ ions. The conformation of MepdG (1) and dGpMe (2) in D2O solution was inferred from vicinal proton-proton, proton-phosphorus and carbon-phosphorus NMR coupling constants and nuclear Overhauser effects (NOE). The chemical shift changes showed that hard Mg2+ ions interact preferentially with the phosphate oxygen atoms in MepdG (1), whereas in the case of dGpMe (2) the interaction with the phosphate oxygen atoms competes with the interaction to the C6=O carbonyl group. Softer Zn2+ and Hg2+ ions were found to show strong binding affinity towards N7 in both MepdG (1) and dGpMe (2). Analysis of J coupling constants and NOEs measured as a function of metal ion concentration revealed that: (i) N → S pseudorotational equilibria are biased towards C2′-endo pseudorotamers in M2+-free MepdG (1) and dGpMe (2) by 68% and 75% at 298K, respectively. Titration of MepdG (1) and dGpMe (2) with Mg2+ ions caused no observable changes in N → S pseudorotational equilibrium, whereas the interactions of Zn2+ and Hg2+ ions with N7 resulted in the shift towards N-type pseudorotamers which can be explained by the strengthening of the anomeric effect as softer metal ions bind to N7 and make the imidazole moiety less electron-rich. (ii) The binding of divalent metal ions to MepdG (1) and dGpMe (2) causes a shift of the syn → anti equilibrium towards anti, which is larger for softer Zn2+ than for harder Mg2+ ions. (iii) The conformational equilibrium across the C4′-C5′ bond (γ torsion) in dGpMe (2) is not affected by the increased concentration of M2+ ions. (iv) βt conformers are preferred by ca. 77% in aqueous solution of MepdG (1) and only small changes of ca. 1 percentage point in βt population have been found upon metal ion binding to MepdG (1). (v) The two-state εt → ε- conformational equilibrium is biased towards εt rotamers by 63.5% in dGpMe (2). Interaction of hard Mg2+ and softer Zn2+ or Hg2+ ions with dGpMe (2) resulted in the minor increase (〈 3 percentage points) in the population of εt conformers.

Notizen: The temperature dependence of NMR spectra of [(L)Rh(cod)]BF4 complexes with L = dppb (1), (R,R)-diop (2) and (R,R)-HO-diop (3) has been examined. Molecular mechanics and ab initio calculations on the [{1,4-bis(dimethylphosphanyl)butane}Rh+(diolefin)] complex predict local energy minima for all twist-chair (TC1, TC2 = TC7, TC3 = TC6, TC4 = TC5) and two boat (B3 = B6 and TB1) conformations. Furthermore, ab initio calculations at the B3LYP/6-31G(d)/LANL2DZ level show that two minima are located in the wide-open region between the TC7 and C4 conformations. Relative B3LYP/6-31G(d) energies of the B3, TC1 and {C4-TC7} conformations are 0.0, 0.71 and 0.97-1.08 kcal mol-1, respectively. Analysis of crystallographic data contained in the Cambridge Structural Database shows that the majority of structures are concentrated in the region {C4-TC7} and close to B3. The symmetrical doublet in the 31P-NMR spectra is assigned to the fast equilibrium {TC7-C4} ⇌ TC1 ⇌ {C5-TC2}. The resonances of the other species are consistent with B3 = B6 geometry. A fused dioxolane ring forces the chelate in diop complexes to adopt the B4 = B5 conformation. For both types of ligand the chair-like conformation is enthalpically preferred at low temperatures (ΔH° = 0.45-0.46 kcal mol-1), whereas the boat-shaped structure predominates at temperatures above 200 K (ΔS° = 0.9-1.3 cal K-1 mol-1). Line-shape analysis provides a boat pseudorotation barrier for complex 1 of ΔG≠ = 5.9 kcal mol-1 and for 2 ΔG≠ = 5.3 kcal mol-1 at 184 K. The free energy of activation at this temperature for the boat-chair interconversion is ΔG≠ = 8.6 kcal mol-1 for complex 1 and ΔG≠ = 8.0 kcal mol-1 for complex 2.

Notizen: The copper(I) compounds [Cu(dppe)2]X [X = BF4-, I-; dppe = 1,2-bis(diphenylphosphanyl)ethane], [Cu(dppp)2]X [X = BF4-,I-; dppp = 1,3-bis(diphenylphosphanyl)propane], [Cu2(dppe)3I2], and [Cu2(dppe)2I2] have been prepared and their structural properties in solution and in the solid state have been determined. 1H-, 13C-, and 31P-NMR spectra in solution [variable temperature and anion (I-) concentrations] and analyses of solids (mass spectra, elemental analyses, and CPMAS 31P-NMR spectra) are interpreted with equilibria in solution that involve two mono- and two dinuclear species. The structures of [Cu(dppe)2]ClO4, [Cu(dppp)2]BF4, and [Cu2(dppe)3I2] · 2 CHCl3 have been analyzed by X-ray crystallography. In all three structures the copper(I) center adopts a distorted tetrahedral geometry.

Notizen: The reaction of [Cp*IrCl2]2 with dilithium 1,2-ortho-carborane-1,2-diselenolate 3 leads to the green 16-electron diselenolene complex [Cp*Ir{Se2C2(B10H10)}] (4) which takes up two-electron ligands such as trimethylphosphane to give the 18-electron diselenolate derivative [Cp*Ir(PMe3){Se2C2(B10H10)}] (5). The molecular structures of 4 and 5 were determined by X-ray crystal structure analysis. The 77Se-nuclear shielding in 4 is lower by almost 500 ppm relative to that in 5.

Notizen: ortho-Palladation of a sterically crowded primary benzylamine, α-phenylneopentylamine, was accomplished in a moderate yield of 50% in the reaction with the weakest of palladation agents (Li2PdCl4) under very mild conditions, due to a steric promotion of an aromatic C-H bond activation. The structure of dimer 1a thus formed and the palladacycle conformation were established on the basis of 1H-NMR spectroscopy of its mononuclear derivatives with [D5]pyridine (3a) and triphenylphosphane (4a), and an X-ray investi-gation of the latter.Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2005/1999/98367_s.pdf or from the author.

Notizen: Migration of coordinated PtII from the endocyclic N(1) site to the exocyclic nitrogen atom in 9-methyladenine occurs at high pH values. The resulting N(6)-platinated complex has been characterized by X-ray crystal structure analysis and by 1H- and 195Pt-NMR spectroscopy. The 1H-NMR spectra show that the PtII(dien) unit at N(6) can adopt either a syn or an anti conformation with respect to the N(1) site, and that protonation of the ring nitrogen atoms N(1) and/or N(7) perturbs the syn/anti equilibrium.

Notizen: -A sea cucumber ganglioside analogue 7 (NGNAα2→ 6Glcβ1→1Cer), which contains a phytosphingosine as a long-chain base and an α-hydroxy fatty acid, has been synthesized. Coupling of the methyl 2-thioglycoside derivative 5 of N-glycolylneuraminic acid with a cerebroside derivative 3, prepared from acanthacerebroside A (1), afforded protected ganglioside analogue 6, which was deprotected to give the corresponding ganglioside 7.

Notizen: A structurally novel 24-membered C3-symmetrical macrolactone 2a, composed of three units of 3,7-dihydroxy-2,4-dimethyloctanoic acid, was isolated from the Indonesian lichen Usnea dasypoga Rohl.

Notizen: The structures of the norbornenyl and norbornyl sulfones exo-5, endo-5 and endo-6 have been determined experimentally, by X-ray analysis, and theoretically by ab initio calculations (HF/6-31+G*). X-ray crystal structure analyses of the lithiated allylic norbornenyl and norbornyl sulfones endo-3/ent-endo-3·2diglyme and endo-4/ent-endo-4·2diglyme revealed dimeric O-Li contact ion pairs devoid of C-Li bonds. The anions of endo-3/ent-endo-3·2diglyme and endo-4/ent-endo-4·2diglyme adopt both the endo conformation (C2-S) and are characterized by in the exo direction pyramidalized anionic C atoms. The degree of pyramidalization of the C2 atom of 3 is higher than that of 4. Ab initio optimizations (HF/6-31+G*) of the structures of the anions of methylenenorbornene I and methylenenorbornane II resulted in local minima featuring non-planar C2 atoms which are pyramidalized in the exo direction in both cases, but to different degrees. In both cases cryoscopy of 3 and 4 in THF at -108.5 °C revealed approximately 1:1 mixtures of monomers and dimers. The sulfones exo-5, endo-5, exo-6 and endo-6 as well as the lithiosulfones 3 and 4 were studied by NMR spectroscopy. 1H-NMR (400 MHz), 13C-NMR (100 MHz) and 6Li-NMR (44 MHz) spectroscopy of 3 and 4 at -100 °C in [D]8THF revealed in each case only one set of signals, independent of the configuration of the starting sulfones. This indicates in both cases that attainment of both the monomer-dimer and the endo/exo equilibria of 3 and 4 is fast on the NMR time scale. According to 6Li{1H}- and 1H{1H}-NOE experiments of 3 and 4 the monomeric and dimeric species endo-3 and endo-4, having endo anions, seem to be preferred in THF solution. Ab initio calculations of the anions of 3 and 4 resulted in structures endo-3(-Li+), exo-3(-Li+), endo-4(-Li+) and exo-4(-Li+) (HF/6-31+G*), whose atomic point charges were calculated by the method of Kollman et al. The C2 atoms of endo-3(-Li+) and endo-4(-Li+) are pyramidalized in the exo direction whereas the C2 atoms of exo-3(-Li+) and exo-4(-Li+) are pyramidalized in the endo direction. According to the calculations, the endo anions are more stable than the exo anions. There is good agreement between the optimized structures of the free anions and the experimentally determined structures of the anions of the contact ion pairs in the crystal. Reactions of 3 and 4 with DX, MeI, EtI, nPrI and nHeI occurred at the C2 atom under the selective formation of the corresponding endosulfones endo-8a-e and endo-9a-e, respectively, in all cases. Thus, an earlier report on the selective formation of the exosulfone exo-9b in the reaction of 4 with MeI has to be revised. Product ratios were independent of the configuration of the starting sulfones and varied with the nature of the electrophile. Selectivities were highest in the case of the norbornyl species 4. Reaction of 3 with PhCHO occurred at the α position (C2) to afford the alcohols endo-8f and exo-8f (88:12) as single diastereomers and at higher temperatures at the γ position (C8), whereas reaction of 4 with PhCHO took place at the γ position even at low temperatures. Methylation of endo-5 and exo-5 at -105 °C by both the stepwise method and by the in situ method gave different ratios of exo- and endo-methylation products. The selectivities of reaction of 3 and 4 with electrophiles have been rationalized by the Curtin-Hammett/Winstein-Holness concepts. It is proposed that endo-3 (endo-4) and exo-3 (exo-4) are conformationally labile on the time scale defined by the rate of their reactions with electrophiles, and are attacked by electrophiles with high selectivities from the exo and the endo face, respectively, because of the shielding by the phenyl group and the direction of the pyramidalization of the anionic C atom. Preferential formation of the endosulfones is thus ascribed to exo attack of electrophiles on endo-3 (endo-4) being faster than endo attack on exo-3 (exo-4) because of Houk's staggering effect. Methylation of 3 and 4 by the in situ method showed 3, whose C2 atom is stronger pyramidalized, to be more reactive than 4. The base-catalyzed H/D exchange of sulfones endo-5, exo-5, endo-6 and exo-6 with NaOCD3 in CD3OD proceeded in all cases with a high degree of retention of configuration.

Notizen: The diastereoselective synthesis of 3-aryl-1,5-bis(2-hydroxyphenyl)-2,4-dimethyl-1,5-pentanediones has been carried out by conjugate addition reactions of 2′-hydroxypropiophenone to 2′-hydroxy-α-methylchalcone derivatives, or in single one-pot reactions of 2′-hydroxypropiophenone with appropriate benzaldehyde derivatives. The structures and stereochemistry of the obtained diastereomers have been determined using various NMR techniques, and the factors determining their formation are investigated and discussed.

Notizen: The borate ester of 1a and 2e exhibits complete quaternization of the boron center. An equilibrium is observed between the two diastereomeric complexes 3 and 4 formed by coordination to the boron center of either amino group of 2e. At -78°C, this equilibrium is slow on the NMR timescale and a diastereomeric ratio of about 3:1 is observed. At room temperature, a rapid equilibration is observed resulting in two NMR resonances (both 1H and 13C) for the dimethylamino groups of 2e in 3/4. Comparison with the NMR characteristics of the analogous borate complexes of 1h and 1j and of 2c and 2d shows that these resonances each correspond to both methyl groups of a single dimethylamino group. The chemical shift difference occurs solely from the difference between the time fractions that the dimethylamino groups are coordinated to the boron center, and forms, therefore, a direct measure of the ratio 3/4. This ratio amounts to 63:37 at room temperature, which was confirmed by a protonation titration experiment. The elucidation of these NMR characteristics of B(1a)(2e) allowed the more rapid evaluation of the enantiotopic group recognition in many other borate complexes, which range from 57:43 to 67:33 at room temperature. The recognition of the (after complexation) diastereotopic dimethylamino groups of 2e in the borate complex B(1a)(2e) was utilized in a consecutive methylation reaction, which yielded enantiomerically enriched ammonium salt 7. The enantiomeric excess proved to be identical to the diastereomeric excess observed in the preceding recognition event. Strong evidence is presented that complex 3 is indeed the major diastereomer present in a solution of 3/4, as expected from molecular models.

Notizen: Caulerpenyne (1), the abundant sesquiterpene of the green seaweed Caulerpa taxifolia, has been epoxidized with dimethyldioxirane. The reaction proceeds with significant regioselectivity and moderate diastereoselectivity, the addition of oxygen occurring preferentially at the C(6)=C(7) double bond thereby giving (6S,7S)- and (6R,7R)-epoxycaulerpenynes 10 and 12 in an approximately 2:1 molar ratio besides a small amount of 10,11-epoxycaulerpenyne as an equimolecular diastereomeric mixture 8. The epoxides underwent rearrangement under acidic conditions; the 6,7-epoxides were easily converted into allylic alcohols, whereas the 10,11 isomers required more drastic acidic conditions and gave complex mixtures containing two diastereoisomeric 1,4-dioxanes and an enynone. The high reactivity of 6,7-epoxycaulerpenynes suggests their involvement in the biogenetic pathways of the alga.

Notizen: Syntheses of nine novel phanes derived from 4,4′-bipyridine incorporating new spacer elements are described together with their structural and spectroscopic properties. Starting from the previously unknown pyridine-bridged bis(4,4′-bipyridinium) dication 2 and various bis(bromomethyl)arenes, macrocycles 3-7 were prepared in a simple heterogeneous liquid-liquid reaction in satisfactory yields. In complementary experiments starting from bis(4,4′-bipyridinium) compounds 12-14 with substituted xylenes as spacers, ring closure was performed with 2,6-bis(bromomethyl)pyridine (1) to furnish compounds 16-18 in low yield. Temperature-dependent NMR-spectroscopic studies of the macrocycles were performed to investigate their conformational behaviour. The X-ray crystal structures for phanes 3,4 and 6 illustrate the preferred anti conformation of the macrocycles in the solid state. Consecutive reactions at the pyridine bridge were not successful; however, anisolophane 7 was converted into nitroanisolophane 11 by simple nitration of the anisolo spacer in excellent yield.

Notizen: From cultures of Melittangium lichenicola, Archangium gephyra and Myxococcus stipitatus, thirteen new β-methoxyacrylate (MOA) fungicides related to myxothiazols (1) have been isolated. Melithiazols A (2a), D (2b), K (2c), and L (2d) are characterized by a thiazoline-thiazole system, whereas melithiazols B (3a), E (3b), F (3c), G (3d), H (3e), I (3f), M (3g), and N (3h) are bis(thiazoles). Melithiazol C (4), as the first representative of this class of compounds, contains only one thiazole ring. The structures were established on the basis of spectroscopic data, and confirmed in the case of melithiazol E (3b), including its relative configuration, by an X-ray structure analysis. The absolute configuration of melithiazols A (2a) and B (3a) was determined by degradation and CD spectroscopy. Antifungal and cytotoxic activities, inhibition of NADH oxidation, and lipophilicities of melithiazols 2-4, myxothiazols 1, and strobilurin-type compounds are compared.

Notizen: Enantiopure piperidines 4 may be accessed in very good overall yields and high stereoselectivity from the bifunctional products 2 of the silyloxy Cope rearrangement of chiral aldol products 1 by sequential nucleophilic addition of primary amines and subsequent hydrogenation. The reaction is proposed to proceed by initial imine formation followed by an intramolecular aza-conjugate addition to the α,β-unsaturated imide. The stereoselectivity is controlled by A(1.2) strain between the imine N-alkyl group and the conjugate double bond. In an alternate approach, polyalkyl-substituted piperidines were prepared by the addition of organozinc reagents to cyanopiperidines readily obtained from the Cope products in the presence of a silver salt.

Notizen: -The asymmetric synthesis of (+)-streptenol A was carried out in ten steps and with high enantioselectivity (ee ≥ 96%). The key steps are the α-alkylation of 2,2-dimethyl-1,3-dioxan-5-one RAMP hydrazone A (1), subsequent deoxygenation and elaboration of the side chain via aldehyde B to furnish (+)-streptenol A in 23% overall yield. In analogy, the enantiomer (-)-streptenol A was synthesized using the corresponding SAMP hydrazone in 18% overall yield.

Notizen: -A ganglioside molecular species [LLG-3 (1)] has been obtained from the water-soluble lipid fraction of the CHCl3/MeOH extract of the starfish Linckialaevigata. On the basis of chemical and spectroscopic findings, the structure of 1 has been elucidated. Negative-ion FABMS provided important information concerning both the structure of the sugar moiety and the molecular mass of the ganglioside. On the other hand, positive-ion FABMS/MS of [M + Na]+ ions obtained in the positive-ion FABMS of the ceramide lactoside (4) derived from 1 indicated the structure of the fatty acid chain of the ceramide moiety. 1 represents a new ganglioside molecular species possessing a 2→11-linked tandem-type disialosyl moiety.

Notizen: -Starting from enones 7 and 8 siloxydienes 9 and 12 were synthesized. Cyclopropanation and subsequent alkylation with sorbyl bromide provided tetrasubstituted siloxycyclopropanes 15 and 16 in good overall efficiency. Their ring cleavage with fluoride reagents gave 1,7,9-decatrienones 5 and 17; the latter was converted into the protected compound 6. The thermal intramolecular Diels-Alder reactions of 5 and 6 were compared with those of related trienones 3 and 4. Octalones 1, 2, 21, and 22 were formed as mixtures of three or four diastereomers. Thus, for the stereoselective construction of natural products such as α-eudesmol or dihydromevinolin alternative reaction conditions for the cycloaddition step have to be developed.

Notizen: Polyphosphane polyoxides with (O)PCP(O) linkages are powerful chelating agents for extraction of actinides from nuclear wastes. They are obtained either by the Michaelis-Arbuzov reaction of chloromethylphosphane oxides and phosphorus(III) esters, or by the reaction of phosphane oxide carbanions with chlorophosphanes. With the latter method, the addition of a phosphane oxide carbanion in excess allowed us to overcome a transmetallation reaction and thereby obtain polyphosphane polyoxides in good yields. The 1H-NMR spectra of the PCH2P groups show the influence of the different R groups attached to the phosphorus atoms. We determined the coupling constants and the chemical shifts of these spin systems.

Notizen: The alkaloids of two coccinellid beetles, Calvia14-guttata and C.10-guttata have been studied. The major alkaloid of these two species is the new piperidinic cis-lactone 1a, for which the name calvine has been coined. The corresponding trans-lactone 1b (2-epicalvine) is also present as a minor constituent (±10%) in both species. We report here the structure determination and the total synthesis of these compounds. Kept in methanolic solution, these lactones undergo epimerisation as well as opening of the lactone ring leading to a complex mixture of nine main components.

Notizen: Two independent syntheses of 5-hydroxy-6-hydroxymethyl-7-methoxy-8-methylflavanone (1), which was supposed to be natural leridol, demonstrated that this structure assignment was wrong and that the natural flavanone leridol was indeed 5-hydroxy-8-hydroxymethyl-7-methoxy-6-methylflavanone (2).