ALBERT

Notizen: The calculated molecular surfaces for some Sandalwood-odor molecules and structurally similar inactive compounds were compared with the calculated mean surface obtained from five Sandalwood odorants included in the set, and their individual agreement and deviations were estimated. Especially the investigation of selected parts of the surfaces seems very promising in finding structure subunits which might be important for an association to a possible receptor site.

Notizen: Catalytic hydrogenation of the Δ3-unsaturated (9R,10 R)- and (9S,10 S)-epoxyenol lactones 3a, b., and 4a, b., respectively, affords, in addition to the expected saturated epoxylactones 5a, b and 7a, b, also open-chain products, i.e. the diastereoisomeric (9R,10R)- and (9S,10S)-9,10-expoxy-8-oxo-4,5-secosteroklastan-5-oic acids 6a, b. and 8a, b. Alkaline hydrolysis of the lactone ring of compounds 5 and 7 and subsequent acetylation of the corresponding hydroxy derivatives give as the major products the open-chain, diasteroisomeric (9R,10R)- and (9S,10S)-4-acetoxy-9,10-epoxy-methyl esters 9a, b and 11a, b, respectively, and, but only in the androstane series, the tetrahydropyran derivatives 10a and 12a, as the minor components.

Notizen: The kinetics of pyridine exchange on trans-[MO2(py)4]+ have been followed by 1H-NMR in CD3NO2 for M = Re, Tc: k298S-1 = (5.5 ± 0.1) × 10-6, 0.04 ± 0.02; ΔH≠/kJmol-1 = 111 ± 3, 101 ± 9; ΔS≠/JK-1mol-1 = +28 ± 10, +68 ± 35. For the Rev complex, pyridine and oxygen exchanges have been measured simultaneously by 1H- and 17O-NMR in deuterated water: k298/s-1 = (8.6 ± 0.2) × 10-6 (py), (14.5 ± 0.3) × 10-6 (oxygen); ΔH≠/kJmol-1 = 111 ± 1, 91 ± 1; ΔS /JK-1mol-1 = +32 ± 3, -32 ± 4. For both complexes, the rate law for pyridine exchange is first-order in complex and zero-order in pyridine; together with the activation parameter values, and the fact that the rate does not depend significantly on the nature of the solvent, this strongly implies the operation of a dissociative mechanism. The ratio of pyridine exchange rates for the Tc and Re complexes at room temperature is ca. 8000. The consequences of these observations for radiopharmaceutical synthesis are discussed.

Notizen: Why Pentose and Not Hexose Nucleic Acids? Part I . Introduction to the Problem, Conformational Analysis of Oligonucleotide Single Strands Containing 2′,3′-Dideoxyglucopyranosyl Building Blocks (‘Homo-DNA’), and Reflections on the Conformation of A- and B-DNA Summary in collaboration with Prof. Dr. C.E. Wintner, Haverford College, Haverford, PA 19041-1392; academic guest, ETH, March and June/July, 1991.Chemical rationalization of the structure of a biomolecule can be sought through consideration of two criteria: first, the relationship between the structure and its biological function; and second, the structure's potential for constitutional self assembly. The latter criterion convers the judgment, by chemical reasoning, of the chance of its preformation, that is, a synthetic event which must have been undergone by any molecular structure in order to have been selected (or to have selected itself) to become a biomolecule. One way to further the task of rationalizing a biomolecule's structure by experimental means is the design, synthesis, and study of structural alternatives which might have become biomolecules on the basis of either criterion, but which do not, in fact, appear in Nature today.In the formation of sugar phosphates from glycolaldehyde phosphate under basic conditions, straightforward and selective formation of rac-hexose 2,4,6-triphosphates is observed in the absence of formaldehyde, while rac-pentose 2,4-diphosphates are dominant, when (0.5 equiv.) formaldehyde is present [1]. This and other observations indicate that hexose sugars should be regarded to have had a chance of preformation comparable with that of pentose sugars. Why, then, did Nature choose pentoses and not hexoses as the sugar building blocks of nucleic acids? The reason must be functional; it must be the case that pentose nucleic acids are biologically superior to potential hexose alternatives. To the extent that biological function is a consequence of molecular structure and reactivity, the origin of this superiority should be decipherable through chemical experiment, that is, through synthesis of hexose nucleic acids, systematic study of their chemical properties, and comparison of these properties with those of their natural counterparts. This has been the object of the present investigation, initiated in 1986. The paper introduces a series of papers which will describe the results of a model study, namely, the synthesis, pairing properties and structure of homo-DNA oligonucleotides.

Notizen: From a MeOH extra of Psiadia trinervia, seven phenolic compounds were isolated by gel filtration and reversed-phase chromatography. Six of them are known compounds, namely 3,4-di-O-caffeoylquinic acid (2), 3,5-di-O-caffeoylquinic acid (3), caffeic acid, and three 3-methoxyflavonoids. Compound 1 is a 3,4-di-O-caffeoyl derviative of (1S,3R,4R,5R)-1,3,4, 5-tetrahydroxycyclohexanecarboxylic acid, a novel steroisomer of (-)-quinic acid. Following hydrolytic treatment of the MeOH extract, ethyl 3-O-caffeoylquinate (4), ethyl 3,4-di-O-caffeoylquinate (5), and ethyl 3,5-O-caffeoylquinate (6) were isolated. The latter three compounds are artifacts. The configuration of 1-3 was established by NMR and CD (exciton chirality method).

Notizen: The carbohydrate-derived lactone phenylsemicarbazones 3 and 4 were prepared from 5 and 8 (Scheme). Treatment with 4-phenylsemicarbazide gave 6 and 7 (77:23) and 9 and 19 (76:24), respectively. Oxidation of 6 and 9 by CrO3-pyridine to 11 and 13, followed by deprotection, yeilded 3 and 4. The structure of 3 was established by X-ray analysis. Enzyme-inhibition studies using revealed that 3 is a competitive inhibitor with Ki = 23 μm. The activity of 4 was examined using N-acetylglucosaminidase from bovine kidney, Aspergillus niger, and Artemia salina. compound 4 was found to be a competitive inhibitor of all three enzymes with Ki values of 0.13, 6.0, and 0.71 μm and KM/Ki values of 6910, 45, and 465, respectively.

Notizen: Radical anions of ten monocyclic and bicyclic azoalkanes containing the azo group in (Z)-conformation, have been fully characterized by their hyperfine data with the use of ESR, ENDOR, and general-TRIPLE-resonance spectroscopy. These azoalkanes are represented by 3,3,5,5-tetramethyl-1-pyrazline (1), 2,3-diazabicyclo[2.2.1]hept-2-ene (4), and 2,3-diazabicyclo[2.2.2]oct-2-ene (9), as well as by their derivatives 2, 3, 5-8, and 10. For all radical anions \documentclass{article}\pagestyle{empty}\begin{document}$1^{- \atop \dot{}}-10^{- \atop \dot{}}$\end{document}, the 14N-coupling constant, aN, is in the range of +0.83 to +0.97 mT; this finding indicates that the spin population is essentially restricted to the π system of the azo group. The 14N-hyperfine anisotropy largely affects the width of ESR lines, particularly at low temperatures. Substantial coupling constants of 7Li-, 23K-, and 133Cs-nuclei point to a close association of the radical anions with their alkakimetal counterions. With the exception of 39K, these nuclei give rise to readily observable ENDOR signals which appear along with those stemming from protons. The prominent hyperfine features of \documentclass{article}\pagestyle{empty}\begin{document}$1^{- \atop \dot{}}-10^{- \atop \dot{}}$\end{document} are discussed.

Notizen: The radical mono-ions of three azoalkanes in which the azo group is connected to the polycyclic alkane moieties at the bridgehead C-atoms, i.e. 1,1′-azonorbornane (1), 1,1′-azotwistane (2), and 1,1′-azobicyclo[3.2.1]octane (3), were studied in fluid solution by ESR spectroscopy. According to the ESR parameters and MO models, the radical cations of 1-3 should be considered as σ radicals, whereas the corresponding radical anions are π radicals. INDO calculations point to a a remarkable dependence of the 14N-coupling constants on the geometry at the N-atoms in the radical cations of aliphatic azo compounds.

Notizen: The use of α,α,α′,α′ -tetraaryl-1,3-dioxolane-4,5-dimethanols ( = TADDOLs;1) as chiral NMR shift reagents (1H, 13C, 19F) is described. In many cases, the ratio of enantiomeric alcohols and amines can be determined under standard conditions of measurement (CDCl3 as solvent, room temperature). The preparation and use of a new type of TADDOL, the tetrakis(dimethylamino) derivative 1d, is described. Menthol, octan-2-ol, and oct-1-yn-3-ol are partially resolved by crystallization of clathrates with 1c and 1d.

Notizen: Reactions of monosubstituted alkenes RCH = CH2 and [Re(η5-C5H5)(CH2Cl2) (NO)(PPh3)]+BF4- give complexes ([Re(η5-C5H5))(CH2=CHR)(NO) (PPh3)]+BF4- (1a-g) in 63-99% yields as mixtures of (RS,SR)- and (RR,SS)-diastereoisomers (1a (R = Me), 66:34; 1b (R = Pr), 63:37; 1c (R = PhCH2), 70:30; 1d (R = Ph), 75:25; 1e (R = i-Pr), 64:36; 1f (R = t-Bu), 84:16; 1g (R = Me3Si), 69:31; Scheme 2). These differ in the C=C enantioface bound to the chiral Re fragment. In most cases, the analogous reactions of RCH=CH2 and [Re(η5-C5H5) (C6H5Cl)(NO)(PPh3)]+ BF4+ give comparable results. When 1a-e, g are heated in PhCl at 95-100°, equilibration to 96:4, 97:3, 97:3, 90:10, 〉 99:〈 1, and 〉 99:〈 1 (RS,SR)/(RR,SS) mixtures occurs (79-99% recoveries; Tables 1 and 2). Thus, thermodynamic enantioface-binding selectivities are much higher than kinetic binding selectivities. This phenomenon is analyzed in detail. A crystal structure of (RS,SR)-1e (monoclinic, P21/c, a = 10.256(1) Å. b = 17.191(1) Å, c = 16.191(1) Å, β = 101.04(1)°, Z = 4) shows that the Re-C(1)-C(2) plane (see Fig.2) is nearly coincident with the Re-P bond (angle 15°), and that the i-Pr group is ‘syn’ to the nitrosyl ligand.

Notizen: A synthetically useful C—C bond formation involving the photochemical addition of quinoxaline-2(1H)-thiones to alkenes is described. Irradiation of the quinoxaline-2(1H)-thiones 1-4 in the presence of the alkenes 7 gave the 2-(2′-mercaptoalkyl)quinoxalines 8-11 in moderate-to-good yields via ring cleavage of an intermediate aminothietane with aromatization of the quinoxaline ring. The latter was formed by [2+2] photocycloaddition of the C=S bond of the quinoxaline-2(1H)-thione and the C=C bond of the alkene.

Notizen: Perylene quinone compounds of natural and syntheitc origin have been investigated for their quantum efficiency of singlet-oxygen production (ΦΔ). The results may be interpreted by a qualitative relation between ΦΔ and the planarity of the sensitizer molecules, highest values (0.8-0.9) being observed where planarity is favoring tautomeric structures. On the other hand, derivatives exhibiting non-planar quinoid structures show lower ΦΔ, and methylated derivatives react photochemically.

Notizen: Multi-O4-phospho-L-tyrosine-containing peptides can be synthesized by the global as well as the buildingblock approach. Thus, we prepared by both strategies the triphosphorylated and the three regioisomeric diphosphorylated insulin-receptor-(1142-1153)-dodecapeptide derivatives 7 and 4-6, respectively, of the parent Thr-Arg-Asp-Ile-Tyr-Glu-Thr-Asp-Tyr-Tyr-Arg-Lys (3). These phosphorylated peptides are valuable tools to study the regioselectivity of dephosphorylation by phosphatases.

Notizen: Michael addition of N-nitroacetyl derivatives 1 of proline esters using KF under phase-transfer catalysis resulted in the formation of adducts 3-9 with chemical yields ranging from 40-90% (Scheme). Stereoselectivity of up to 51% was obtained on addition of benzyl N-(nitroacetyl)-L-prolinate (1a). The absolute configuration at the newly created chiral centre was established in the case of 9 by carrying out a reductive acylation and comparing the product 10 with an authentic sample of ethyl N-(O5-ethyl N2-acetyl-L-glutam-1-yl)-L-prolinate (L, L-10).

Notizen: By unambiguous methods, (Z)- and (E)-2, 3-dimethyl(1, 1, 1, 4, 4, 4-2H6)but-2-enes (3) were synthesized and transformed to the epoxides 4 with 3-chloroperbenzoic acids. Both the isotopomeric olefins and the epoxides are detected separately by 1H-NMR at 400 MHz. Epoxidation of (Z)-3 with [RhICl(PPh3)3]/cumene hydroperoxide resulted in a 1: 1 mixture of (Z)- and (E)-4, while reaction of (Z)-3 with [FeIII(tpp)]Cl/PhIO gave only (Z)-4 (tpp = tetraphenylporphyrin).

Notizen: A regio- and stereoselective didehydrodimerization procedure, whose key step involves the anodic oxidation, allows the conversion of β-anilinoacrylic alkaloids belonging to the Aspidosperma class, typified by tabersonine (1) and its 3-oxo derivative 2, into the hitherto unknown 16,10′-didehydro dimers 3 and 7, respectively.

Notizen: Synthesis of (6R, all-E)-Neoxanthin and Related Allenic CarotenoidsWe present the first synthesis of enantiomerically pure neoxanthin (1) by a Wittig-Horner condensation between the ylide from the novel diethyl 12′-apo-15, 15′-didehydroviolaxanthin-12′-phosphonate (35) and the allenic C15-aldehyde 31 (Scheme 4) via the crystalline 15, 15′-didehydroneoxanthin (36; 70% yield). After partial hydrogenation of the triple bond of 36 and isomerisation of the (15Z)-intermediate 37, neoxanthin (1) was obtained in good yield. Similar syntheses gave (15Z, 9′Z)-neoxanthin (45; Scheme 5) and (9Z)-15, 15′-didehydroneoxanthin (47; Scheme 6). Comparison of the physical data of synthetic 1 with those of a freshly isolated sample of neoxanthin from the flowers of Trollius europaeus confirmed their identity. The unusually low melting point of 1 is caused by a very easy thermal isomerisation into a mixture of the neochromes 4 and 5 (Scheme 1). Such a thermal rearrangement is not observed with 15, 15′-didehydroneoxanthin (36). To explain this, we assume a zwitterionic excited state of the allenic group that induces the rearrangement of the violaxanthin end group into the furanoid epoxide (Scheme 7).

Notizen: Three new saponins, alatoside A-C (4a, 5, and 6a, resp.), with a 18,19-secours-12-ene skeleton were isolated from the aerial parts of Sesamum alatum THONN. (Pedaliaceae) by preparative liquid chromatography. Their structures were elucidated by spectroscopic methods, including X-ray diffraction analysis, and by chemical degradation (acidic and enzymatic hydrolyses). In addition, verbascoside (1) and two cyclohexylethanol derivatives, rengyol (2a) and isorengyol (3a), were isolated and identified.

Notizen: The 1D- and 2D-6Li, 6Li-INADEQUATE experiments are described as new tools for the detection of scalar coupled nonequivalent 6Li nuclei in organolithium clusters. Practical applications of these sequences are demonstrated for the 6Li-NMR spectra of (E)-1-lithio-2-(2-lithiophenyl)-1-phenylhex-1-ene (1) and (E)-2-lithio-1-(2-lithiophenyl)-1-phenylpent-1-ene (2), where signals due to dimers and monomers can be distinguished. The performance of the 2D-6Li, 6Li-INADEQUATE and the 6Li, 6Li-COSY-45-LR experiment are compared. The 6Li chemical shifts of 1 and 2 are discussed.

Notizen: [2.2] Paracyclophan-1-ene (1) and [2.2] paracyclophane-1,9-diene (6) apparently act as dienophiles with inverse electron demand and smoothly react with dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate (2a) at room temperature forming dihydropyridazine adducts, which are dehydrogenated to the pyridazino-anellated [2.2] paracyclophanes 5a and 8a, respectively. The molecular structure of 5a is determined by X-ray crystal-structure analysis. Under more rigorous conditions, phenyl-substituted derivatives 5b and 8b are obtained from 1 and 6, respectively, with 3,6-diphenyl-1,2,4,5-tetrazine. Compounds 1 and 6 are less reactive dienophiles than other strained cyclic olefins as shown by kinetic measurements.

Notizen: Tris(trimethylsilyl)silane (2) is an efficient hydrosilylating agent of 1,6-dienes 1 operating via a free-radical chain mechanism. The intermediate alkyl radical 3 attacks the second olefinic bond of the diene 1 and forms cyclopentylalkyl radical 4. Using a low concentration of the hydrogen donor 2, a radical substitution reaction at the Si-center of cis-4 occurs and yields the bicyclic silane 6. The rate of this homolytic substitution at the Si-atom is 2.4 · 105 s-1 (80°).

Notizen: (R)- and (S)-α-ionone ((R)- and (S)-1, resp.) were prepared from (R)- and (S)-α-damascone ((R)- and (S)-3, resp.) without racemization in 48% yield employing a new enone transposition. The described transposition is complementary to existing methods whose application is often prohibited by the structural requirements of the substrate. The now easily accessible α-ionones of desired absolute configuration are useful as chiral building blocks for terpenoid synthesis.

Notizen: Catalytic double osmylation is described for a series of cyclohexadienes in acetone/H2O in the presence of the co-oxidant N-methylmorpholine N-oxide (NMO). The formation of polyols occurred stereospecifically with cyclohexadienes 3,7, and 11a, leading thereby to tetrols 5a, and 9a and to allo-inositol (14a), respectively. To the contrary, trans-cyclohexadiene-diol 15a gave a mixture of the stereoisomeric inositols 18a (epi), 19a (neo), and 20a (chiro). High-field NMR let to clearcut conformational analyses of the polyhydroxylated derivatives.

Notizen: Esculetin (1) and the novel compounds 5-chloroesculetin (5) and 5-bromoesculetin (6) were obtained from a light-induced cyclization of trans-caffeic acid (3) catalyzed by [FeNa(edta)] and/or H2SO4, HCI, or HBr (Scheme 1). The experimental conditions for trans-cis-isomerization of the cinnamic-acid derivative 3 and subsequent non-enzymatic cyclization were described. The photoperiod and the presence of air and iron-chelate catalyst are shown to be important parameters that markedly affect yields. The reactions probably occur by a free-radical mechanism involving a photo-initiated one-electron redox process (Scheme 2).

Notizen: The protected disaccharide 44, a precursor for the synthesis of allosamidin, was prepared from the glycosyl acceptor 8 and the donors 26-28, best yields being obtained with the trichloroacetimidate 28 (Scheme 6). Glycosidation of 8 or of 32 by the triacetylated, less reactive donors 38-40 gave the disaccharides 46 and 45, respectively, in lower yields (Scheme 7). Regioselective glycosidation of the diol 35 by the donors 38-40 gave 42, the axial, intramolecularly H-bonded OH—C(3) group reacting exclusively (Scheme 5). The glycosyl acceptor 8 was prepared from 9 by reductive opening of the dioxolane ring (Scheme 3). The donors 26-28 were prepared from the same precursor 9 via the hemiacetal 25. To obtain 9, the known 10 was de-N-acetylated (→ 18), treated with phthalic anhydride (→ 19), and benzylated, leading to 9 and 23 (Schemes 2 and 3). Saponification of 23, followed by acetylation also gave 9. Depending upon the conditions, acetylation of 19 yielded a mixture of 20 and 21 or exclusively 20. Deacetylation of 20 led to the hydroxyphthalamide 22. De-N-acetylation of the 3-O-benzylated β-D-glycosides 11 and 15, which were both obtained from 10, was very sluggish and accompanied by partial reduction of the O-allyl to an O-propyl group (Scheme 2). The β-D-glycoside 30 behaved very similarly to 11 and 15. Reductive ring opening of 31, derived from 29, yielded the 3-O-acetylated acceptor 32, while the analogous reaction of the β-D-anomer 20 was accompanied by a rapid 3-O→4-O acyl migration (→34; Scheme 4). Reductive ring opening of 21 gave the diol 35. The triacetylated donors 38-40 were obtained from 20 by debenzylidenation, acetylation (→36), and deallylation (→37), followed by either acetylation (→38), treatment with Me3SiSEt (→39), or Cl3CCN (→ 40).

Notizen: Bare FeO+ reacts in the gas phase with benzene at collision rate (k = 1.3 × 10-9 cm3 molecule-1 s-1), giving rise to the formation of Fe(C6H4)+/H2O(5%), Fe(C5H6)+/CO(37%), Fe(C5H5)+/CO/H. (2%), and Fe+/C6H5OH (56%). Neither the reaction rate nor the product distribution are subject to a significant kinetic isotope effect, thus, ruling out several mechanistic variants described in the literature to the operative for ‘analogous’ arene oxidation processes in solution. A mechanism is suggested which is in keeping with the experimental findings, and which also accounts for some remarkable results obtained, when two [Fe, C6,H6H6O]+ isomers are generated and subjected to a neutralization-re-ionization experiment in the gas phase.

Notizen: Quinic acid (1a), shikimic acid (2), and their derivatives were acylated in organic solvents by several lipases and by the protease subtilisin Carlsberg. The most satisfactory results were obtained with methyl (or benzyl) quinate (7a (or 8a)) and lipase from Chromobacterium viscosum adsorbed on Celite, which showed an overshelming preference towards the acylation of OH-C(4). Under optimized conditions, the syntehtically useful 4-O -acetylquinate 8d was isolated in ca. 90% yield. On the other hand, acylation of methyl shikimate (10a) showed no regioselectivity with any of the enzymes tested. A possible rationale for the different behavior of Chromobacterium viscosum lipase towards 7a and 10a is given, comparing the conformations of these two molecules, as deducted from 1H-NMR and molecular-mechanics calculation.

Notizen: A general synthetic strategy for the preparation of polyazamacrocycles containing long aliphatic chains is reported. These compounds are 22- or 24-membered hexaazamacrocycles incorporating two diethylenetriamine subunits (H2NCH2CH2NHCH2CH2NH2) linked together either by two CH2CH2OCH2CH2 (see 4-6), two tetramethylene (see 7), or two pentamethylene (see 8) fragments. Whereas for compound 4, one of the centrally located amine functionalities of the triamine subunit bears a hexadecyl chain, for compound 5, two of such chains are centrally attached to both subunits. In macrocycles 6-8, all six amino functionalities bear hexadecyl chains. Compounds 4-8 are potential candidates for the construction of selective chemical sensors such as specific electrodes for adenosine mono-, di-, and tri-phosphate. They may also be used for nucleoside polyphosphates extraction and/or transport.

Notizen: The absolute configuration of the gamete-releasing and -attracting pheromone 2-vinyl-3-(5′-vinylcyclopent-2′-enyl)oxirane ( =(+)-caudoxirene; (+)-1) of the marine brown alga Perithalia caudata is established as (2R,3R,1′S,5′S). Highly diastereoselective syntheses and the biological activities of three diastereoisomers of 1 are described. Compound (+)-(2R,3R,1′S,5′S)-1 is the first fully characterized epoxypheromone from marine brown algae (Phaeophyceae).

Notizen: A new series of channel-type molecules presenting the features of potential transmembrane structures is described. They result from the grafting of amphiphilic side chains on a β-cyclodextrin derivative 3 that constitutes the organizing core. They belong to the ‘bouquet’ family (B). Compounds bearing poly(oxyethylene) side chains, BCDo16 and 17, and their polymethylene analogues BCDC18 and 19, were synthesized. The properties investigated emphasize the suitability of such molecules to be incorporated into lipid bilayer membranes.

Notizen: Reactions of 4-Bromo-1,6-methano[10]annulene-3-carbaldehyde: Syntheses of 3,4-Heteroanellated 1,6-Methano[10]annulenesSimilarly to β-chlorovinyl ketones, the title compound 1 reacts with dinucleophiles to give the 3,4-heteroanellated 1,6-methano[10]annulenes 2-4, 6, and 12-16, containing thiophene, pyrazole, pyrimidine, and thiazepine rings (Schemes 2 and 3). On reaction of 1 with tert-butylhydrazin, an unusual Michael-addition-dehydrogenation sequence, resulting in 2,3-anellation of a pyrazole ring (→5), is observed. Synthetic as well as some mechanistic aspects are briefly discussed.

Notizen: The exchange of butane with deuterium on a nickel/alumina catalyst is studied over a wide range of temperatures (50-230°) and for three hydrocarbon/deuterium ratios. The initial distribution is used to propose a reaction scheme by considering different adsorbed species such as: alkyl-(α), alkene-(α, β) and allyl-(α,β,γ) species, where α, β, and γ are different C-atoms. It is assumed that each adsorbed species can either desorb directly while exchanging one, two, and three H-atoms or undergo multiple exchange before desorption. It is shown that by reducing the activity of the catalyst a back-exchange of the fully deuterated species sets in a lower temperature; a systematic deviation of all model calculations for the estimation of the concentrations of the C4HD9 and C4D10 is, thus, explained. The exchange of CH3CD2CD2CH3 and CD3CH2CH2CD3 with H2 and D2 is also studied, and similar results are obtained as with exchanges of CH3CD2CH3 and CD3CH2CD3. With the help of very-high-resolution mass spectra, it is shown that the initial degree of deuteration, i. e. the degree of deuteration after one adsorption step, is 84% for the methylene and 57% for the methyl group respectively. The hydrogenolysis reactions of butane is studied in the same system between 180° and 230°. A wide range of conversion is covered, and the product distributions are fitted to kinetic equations in order to obtain the initial rate constants. On the nickel/alumina catalyst one or several C-C bonds are broken before the desorption of the species. Under the conditions used in these experiments, the surface cracking is the rate-limiting step. An isotope effect is observed for the decomposition in D2, the production of propane being favored.

Notizen: The title compund, 1a, has been synthesised in racemic form from ethyl (E)-4-chloro-3-ethoxybut-2-enoate in 43% overall yield in five steps. Several routes to the final product are described, but the most efficient involves hydrogenation of a C(5)-unsubstituted tetramic acid 5b. The instability of this class of compounds required the use of a catalyst which could operate under very acidic aqueous conditions, a role that was successfully filled by a 5% Ru/C catalyst.

Notizen: Synthesis of 2-Substituted and 2,3-Disubstituted Alkyl- und Aryl-thiophenes and Related 2,3-Anellated Thiophene Derivatives, Using Ketones and Carbonodithioic Acid O-Ethyl S-(2-Oxoethyl) Ester as the Building BlocksA simple method to synthesize 2-substituted and 2,3-disubstituted alkyl- and aryl-thiophenes as well as related 2,3-anellated thiophenes 6, starting from ketones 1 as C2-fragment and the S-protected carbonodithionic-acid derivative 3 as a C2S-fragment is described. The aldols 4 are intermediates of the two step process.

Notizen: A set of derivatives of cyclopentaneacetic acid cis-substituted at position 3 by nucleoside bases (both purines and pyrimidines) were prepared and characterized (see 11, 14, and 23a, b; Schemes 2-4). These molecules are carbocyclic analogs of 2′,3′-dideoxy-5′-homonucleosides. In this synthesis, the skeleton was constructed from norbornanone and a novel method based on Mitsunobu chemistry used for the introduction of nucleoside-base substituents. The scope of this method was further explored via the preparation of a cyclobutyl analog of dideoxyguanosine (see 17, Scheme 3).

Notizen: α-Chamigren-3-one (+)-8 bearing an axial CI-atom at C(8) exists as a largely dominant conformer with Me - C(5) at the envelope-shaped enone ring pointing away from CIax-C(8) at the cyclohexane ring (= B) in the ‘normal’ chair conformation, as shown by 1H-NMR. In contrast, the α-chamigren-3-ols (+)-9 and (+)-10, obtained from hydride reduction of (+)-8, show a temperature-dependent equilibrium of conformers where the major conformers have ring B in the inverted-chair (and twist-boat for (+)-9) conformation to avoid repulsions between Me-C(5) and CIax-C(8) (Scheme 1). This is in agreement with the conformation of the epoxidation product (+)-12 of (+)-9 where Me-C(5) is pushed away from CIax-C(8) in a ring-B chair similar to that of (+)-8 (Scheme 2). Introduction of a pseudoequatorial Br-atom at C(2) of (+)-8, as in enone (+)-15 (Scheme 3), does not affect the conformation; but a pseudoaxial Br—C(2) experiences repulsive interactions with Heq-C(7), as shown by the 1H-NMR data of the isomeric enone (+)-16 where the ‘normal’-chair conformer Cβ-16 is in an equilibrium with the inverted chair conformer ICβ-16 (Scheme 3). These results and the accompanying paper allow a unifying view on the conformational behavior of marine polyhalogenated α-chamigrenes. This view is supported by the acid-induced isomerization of α-chamigrene (+)-9 (inverted chair) to β-chamigrene (+)-17 (‘normal’ chair; Scheme 4), the driving force being the lesser space requirement of CH2=C(5) than of Me-C(5). This explains why β-chamigrenes are so common in nature.

Notizen: The tris-carotenoid macrobicycles 1 and 2 were obtained in good yields in a one-step macrobicyclisation condensation between the tripode N(CH2CH2NH2)3 and the polyolefinic dialdehydes 5 and 6. They form dinuclear cryptates by complexation of two CuI ions. The crystal structure of the tris-carotenoid compound 2 confirms that it contains three parallel polyolefinic strands. These substances may formally be considered as prototypes of molecular ‘cables’ formed by three electron-conducting molecular wires.

Notizen: Coprine (1), a toxine of the mushroom Coprinus atramentarius, was synthesized starting from the 2-amino and 1-carboxy-protected L-glutamic acids 4 and 12. Compound 4 was first decarboxylated by a radical chain reaction to bromide 5 which underwent ring closure to cyclopropanecarboxylate 6 on treatment with NaH (Scheme 1). Subsequent oxidative electrolysis of 7 to form tert-butyl N-(1-ethoxycyclopropyl)carbamate (8) and acidic hydrolysis yielded the 1-aminocyclopropanol hydrochloride (9). Selective cleavage of the amino-protecting group of 8 (→ 10 or 11), coupling of the corresponding amine 13 with L-glutamic acid 12, and acidic hydrolysis of the resulting L-glutamine derivative 17 yielded O-ethylcoprine (3) and coprine (1).

Notizen: The 1,7-dideaza-2′-deoxyadenosine (c1c7Ad; 1) was converted into building blocks 3a,b for solid-phase oligodeoxyribonucleotide synthesis. Testing various N-protecting groups - benzoyl, phenoxyacetyl, [(fluoren-9-yl)methoxy]carbonyl, and (dimethylamino)methylidene - only the latter two were found to be suitable (1 → 4b, d). Ensuing 4,4′-dimethoxytritylation of 4d and phosphitylation afforded the 3′-phosphonate 3a or the 3′-[(2-cyanoethyl)diisopropylphosphoramidite] 3b. Self-complementary oligonucleotides with alternating dA or c1c7Ad and dT residues (7 and 8) as well as palindromic oligomers such as d(C-G-C-G-c1c7 A-c1c7 A-T-T-C-G-C-G) (10) and d(G-T-A-G-c1c7 A-c1c7 A-T-T-C-T-A-C) (12) were synthesized. Duplex stability was decreased because 1 cannot form Watson-Crick or Hoogsteen base pairs if incorporated into oligonucleotides. On the other hand, the structural modifications in 10 and 12 forced these palindromic oligomers to form hairpin structures.

Notizen: Synthesis and Photochrmic Characteristics of 1,3-Dihydrospiro[2H-indole-2,3′-[3H-]pyrimido[5,4-f][1,4]benzoxazines] and 1,3-Dihydrospiro[2H-indole-2,7′[7H]thiazolo[5,4-f][1,4]benzoxazines]Two new series of 1,3-dihydrospiro[2H-indole-ozazine] derivatives were synthesized, the 1,3-dihydrospiro[2H-indole-2,3′-[3H]pyrimido[5,4]pyrimido[5,4-f][1,4]benzoxaines] 4-10 and the 1,3-dihydrospiro[2H-indole2,7′-[7H]thiazolo-[5,4-f][1,4]benzoxaines] 11-17. These series extend the available range of photochromic properties (rate constant of thermal bleaching, UV/VIS spectrum of the opened coloured form, and photocoloration yield), an interesting feature of variable-transmission materials. The synthesis of these compounds (Scheme 1) required the preliminary synthesis of intermediate β-hydroxy-α-nitrosotherocycles 18 and 19 (Scheme 2). Important amounts of a coloured, non-photochromic, stable secondary product (See 20) were found in the condensation in the spiro[indole-thiazolobenzoxazine] series. The photochromic characteristics of the new derivatives were determined using a flash-photolysis apparatus coupled to a fast-scanning spectrometer. The role of the heteroatoms in the oxazine moiety and the role of substitutents in the indole moiety were investigated quantitatively through the study of the photochromic properties and the solvent effects. The presence of an S-atom gives rise to interesting properties which open up new prospects for synthesis and application.

Notizen: The titanates derived from α,α,α′,α′-tetraaryl-1,3-dioxolane-4,5-dimethanols (TADDOLs, prepared from tartrate) act as catalysts for enantioselective additions of dialkylzinc compounds to aldehydes. For the standard reaction chosen for this investigation of the mechanism, the addition of diethylzinc to benzaldehyde, there is very little change of selectivity with different aryl substituents on the TADDOLate ligands (Tables 2-4, examples). With 0.02 to 0.2 equiv. of the chiral titanates, selectivities above 90% are observed only in the presence of excess tetraisopropyl titanate! According to NMR measurements (Fig. 2), the chiral bicyclic titanate and the achiral titanate do not react to give new species under these conditions. From experiments with different stoichiometries of the components, and with different achiral or chiral OR groups on the Ti-atom of the seven-membered ring titanate, it is concluded (i) that a single chiral titanate is involved in the product-forming step, (ii) that the bulky TADDOLate ligand renders the Ti-center catalytically more active than that of (i-PrO)4Ti, due to fast dynamics of ligand exchange on the sterically hindered Ti-center (Table 5, Fig. 3), and (iii) that the role of excess (i-PrO)4Ti is to remove - by ligand exchange - the product alkoxides (R*O) from the catalytically active Ti-center (Scheme 4, Table 6). Three new crystal structures of TADDOL derivatives (two clathrates with secondary amines, and a dimethyl ether) have been determined by X-ray diffraction (Figs. 5-7), and are compared with those previously reported. The distances between the C(aryl)2O oxygen atoms in the C2- and C1-symmetrical structures vary from 2.58 to 2.94 Å, depending upon the conformation of their dioxolane rings and the presence or absence of an intramolecular H-bond (Fig. 8). A single-crystal X-ray structure of a spiro-titanate, with two TADDOLate ligands on the Ti-atom, is described (Fig. 9); it contains six different seven-membered titanate-ring conformations in the asymmetric unit (Fig. 10), which suggests a highly flexible solution structure. The structures of Ti TADDOLate complexes are compared with those of C2-symmetrical Ru, Rh, and Pd disphosphine chelates (Table 7). A common topological model is presented for all nucleophilic additions to aldehydes involving Ti TADDOLates (Si attack with (R,R)-derivatives, relative topicity unlike; Fig. 11). Possible structures of complexes containing bidentate substrates for Ti TADDOLate-mediated ene reactions and cycloadditions are proposed (Fig. 12). A simple six-membered ring chair-type arrangement of the atoms involved can be used to describe the result of TADDOLate-mediated nucleophilic additions to aldehydes and ketones, with Ti, Zr, Mg, or Al bearing the chiral ligand (Scheme 6). A proposal is also made for the geometry of the intermediate responsible for enantioselective hydrogenation of N-(acetylamino)cinnamate catalyzed by Rh complexes containing C2-symmetrical diphosphines (Fig. 13).

Notizen: A new base pair (called κ-π) of Watson-Crick type, with an H-bond pattern different from that in A-T and G-C base pairs, has been recently synthesized by Benner and coworkers and shown to be stable and incorporable into duplex DNA and RNA by polymerases. This new base pair, which contains three H-bonds, is compared with G-C, in the framework of modern dynamical theory of quantum nonlocality and quantum correlations (also called Einstein-Podolsky-Rosen correlations). Connection with the traditional treatment of proton transfer in DNA base pairs, which uses the adiabatic approximation (thus considering the protons as classical particles), is explicitly made. As a result, the dynamics of the H-bond pattern of G-C is shown to exhibit a specific quantum-mechanical phase stability (or: rigidity, stiffness), which is clearly missing in the case of κ-π. This finding is discussed and illustrated, also in connection with recent quantum chemical calculations of proton transfers in DNA base pairs. Additionally, certain speculations concerning a probable ‘evolutionary advantage’ of G-C with respect to κ-π are shortly considered.

Notizen: The leaves of a New Caledonian celastraceae, Pleurostylia opposita (WALL.) MERRILL-METCALF, have yielded three new spermidine alkaloids, 7-hydroxypleurostyline (1), 7-hydroxycelacinnine (2), and 7′-hydroxy-7′,8′-dihydropleurostyline (3), as minor basic constituents, together with three related alkaloids pleurostyline (4), celacinnine (5), and celallocinine (6).

Notizen: 6-Thioxanthopterin (13) was synthesized in four steps starting from 2-amino-4-(penthyloxy)pteridine (3) via the 8-oxide 4, its subsequent interconversion to the 6-chloro (7) and 6-thio derivative (12) and final hydrolysis of the pentyloxy group. 7-Thioisoxanthopterin (15) was derived analogously from 2-amino-4-(pentyloxy)pteridine-7(8H)-thione (14) by alkaline hydrolysis. The various 6- and 7-thiopteridines were methylated to give the corresponding 6- (10, 11) and 7-(methylthio) derivatives (16, 17). The newly synthesized compounds have been characterized by elemental analyses, their UV spectra, and the determination of the acidic and basic pKa values. The spectral relationships are discussed in detail.

Notizen: The syntheses and characterization of four new linear pentadentate ligands and their CoIII complexes are described: N,N′-[(pyridine-2,6-diy)bis(methylene)]bis[sarcosine] (sarmp), N,N′-[(pyridine-2,6-diyl)bis(methylene)]bis[(R)- or (S)-proline] ((R,R)- or (S,S)-promp), N,N′-[(pyridine-2,6-diyl)bis(methylene)]bis[N-(methyl)-(R)- or (S)-alanine] ((R,R)- or (S,S)-malmp); 2,2′-[pyridine-2,6-diyl]bis[(S)- or rac-N-(acetic acid)pyrrolidine] ((S,S)- or rac-bapap). The complexes were characterized and, with but one exception, complex formation is stereospecific: Δ-exo-(R,R) (or Λ-exo-(S,S)) for promp and Λ-(R,R) (or Δ-(S,S)) for bapap. The exception is [Co((R,R)- or (S,S)-malmp)H2O]ClO4 for which two forms are obtained, to which Λ-endo-(R,R) (or Δ-endo-(S,S)) and, tentatively, Δ-unsymmetric-(R,R)- (or Λ-unsymmetric-(S,S)-) configurations are assigned. X-Ray crystal structures are presented for the complexes [Co(sarmp)H2O]ClO4, [Co((S,S)-promp)H2O]ClO4, [Co(rac-bapap)H2O]ClO4 and endo-[Co(rac-malmp)H2O]ClO4. Ligand acid dissociation and CoII and FeII complex-formation constants are reported.

Notizen: The molecular structures of the title compounds 3 and 5 were investigated by NMR and X-ray structural methods. The NMR results suggest two equivalent halves for both molecules. The X-ray study shows an approximate mirror plane for 3 and an approximate twofold axis for a significant portion of the macrocycle of 5.

Notizen: In two steps, 5,5-dimethyl-1H-pyrrol-2(5H)-one (3a) was prepared from 5,5-dimethylpyrrolidine-2,4-dione ( = dimethyltetramic acid; 4) in 71% overall yield (Scheme 1) and further converted to N-substituted derivatives 3b-f via acylation, alkylation, or methoxycarbonylation of its anion (Scheme 2). The substituents on the N-atom exert a strong influence on the photochemical reactivity ([2 + 2] photocycloaddition to 2,3-dimethylbut-2-ene, photocyclodimerisation, photoreduction) of these aza-enones 3 (Scheme 3). In general, N-alkyl compounds react much slower and with less efficiency than either the (N-unsubstituted) title compound 3a or its N-acetyl and N-(methoxycarbonyl) derivatives 3e and 3f, respectively. These compounds behave similarly to the corresponding lactone, 5,5-dimethyl-2(5H)-furanone, studied previously.

Notizen: Mechanistic questions regarding the reductive cleavage of sulfonium ions by the NiI form of coenzyme F430 pentamethyl ester (F430M) were addressed in a series of kinetic studies and isotope labeling experiments. In neat DMF, methane formation from dialkyl(methyl)sulfonium ions consistently showed a delay time of ca. 1 h. In the presence of excess propanethiol, no delay was observed and methane formation followed pseudo-first-order kinetics with a logarithmic dependence of the initial rate on the concentration of propanethiol. From the temperature dependence of the reaction rate, an estimate for the activation parameters of ΔH# = 49 kJ mol-1 and (apparent) ΔS# = -114 J K-1 mol-1 was derived. The observation of deuterium incorporation into methane from (CH3)2CHOD, but not from (CH3)2CDOH, indicates that the fourth H-entity is introduced into CH4 as a proton, and that free CH3 radicals are not involved. In contrast to the reaction with the homogeneous one-electron reductant sodium naphthalide, the F430M-catalyzed reduction of mixed dialkyl(methyl)sulfonium ions showed a pronounced selectivity for the cleavage of Me—S over that of alkyl-S (alkyl ≠ Me) bonds. Mechanisms that are consistent with these results, as well as possible explanations for the time delay and the apparent highly negative entropy of activation, are discussed.

Notizen: Why Pentose and Not Hexose Nucleic Acids? Part II . Preparation of Oligonucleotides Containing 2′,3′-Dideoxy-β-D-glucopyranosyl Building Blocks(7)This paper describes the preparation of the 2′,3′-dideoxy-β-D-glucopyranosyl-( = 2′,3′-dideoxy-β-D-erythro-hexopyranosyl)-derived nucleosides of the five bases adenine, cytosine, guanine, thymine, and uracil ( = ‘homo-de-oxyribonucleosides’) as well as the synthesis of oligonucleotides derived from them. The methods used for both nucleoside and oligonucleotide synthesis closely follow the known methods of synthesis in the corresponding series of natural 2′-deoxyribonucleosides and oligonucleotides. The efficient methods of automated DNA synthesis proved to be fully applicable to the synthesis of homo-DNA oligonucleotides, the only change necessary for achieving satisfactory coupling yields being a slight lengthening of the coupling time. Homo-DNA oligonucleotides with chain lengths of up to twelve nucleoside units were assembled on solid support either manually or on a commercial DNA synthesizer in scales of 0.4 μmol to as much as 200 μmol and were purified by either reversed-phase or ion-exchange HPLC to single-peak purity according to both chromatographic systems (estimated purity 〉 95%). The choice of the specific base sequences to be synthesized was determined primarily by the constitutional problems of base pairing that emerged from experimental observations made in the course of systematic studies of the pairing properties of homo-DNA oligonucleotides. About 100 homo-DNA sequences were prepared for this purpose. Their pairing properties will be described in Part III of this series; the present paper is restricted to the characterization of the purity and constitutional integrity of a few selected (single-stranded) oligonucleotides by 1H-, 31P-, and 13C-NMR spectroscopy as well as by FAB and time-of-flight mass spectroscopy.The English Footnotes to Schemes 1-9, Fig. 1-12, and Table 1 provide an extension of this summary.

Notizen: The copper-catalyzed oxidation of ascorbic acid (AscH2) has been studied with a Clark electrode in aqueous MeCN. CuI or CuII may be equally used as the source of metal ion, without influence on the rate law. At sufficiently high [MeCN], the rate of the overall reaction is essentially given by the rate of CuI autoxidation: the reaction is of first order with respect to [CutotI,II] and [O2] and shows an inverse-square dependence on [MeCN] as observed for the autoxidation of Cuaq+. The pH dependence is complicated by the combination of the intrinsic pH effect on autoxidation with an additional term in the rate law which is directly proportional to [AscH-]. The latter term is explained by direct oxidation of the organic substrate by the primary dioxygen adduct of CuI, CuO2+. For [MeCN] 〈 0.7M, a gradual and pH-dependent transformation of this rate law and deviation from the first-order dependence on [O2] is indicated.

Notizen: The fate of tetrahydrolipstatin (1) incubated with human carboxyl-ester lipase (HCEL) was investigated. The primary metabolite was identified as δ-(N-formyl-L-leucyloxy)-β-hydroxy acid 2a with conserved configuration. It is formed by attack of the active-site serine of HCEL at the carbonyl C-atom of the β-lactone ring of 1 followed by hydrolysis of the intermediate serine ester. Further products isolated were identified and a complete degradation scheme is proposed.

Notizen: ESR and cyclic voltammetry investigations show that isomerization of the radical cation of cis-1,1′-azonorbornane (cis-1) to the trans-radical ion proceeds too fast in solution for direct investigation of the cis-radical ion even at -78°. The facile isomerization of the radical cation is in agreement with PM3 calculations proposing an activation barrier of only 17 kJ/mol. As a consequence, quantitative cis → trans isomerization of 1,1′-azonorbornane can effectively be accomplished by addition of catalytic amounts of one-electron oxidants. This is the first evidence for a radical-cation-catalyzed cis → trans isomerization of azo compounds.

Notizen: Irradiation (λ = 350 nm) of newly synthesized 2-acetyl- or 2-methyl-2-(alk-2-enyl)furan-3(2H)-ones 1 and 2-acetyl- or 2-methyl-2-(prop-2-enyl)thiophen-3(2H)-ones 2 affords the corresponding 1-acetyl- or 1-methyl-substituted 7-oxa- and 7-thiatricyclo[3.2.1.03,6]octan-2-ones 10 and 11, respectively, via regioselective intramolecular [2 + 2] photocycloaddition in 65-95% yield (Scheme 2). The 1-acetyl-substituted O-derivatives 10b and 10c undergo ring opening on treatment with MeONa in MeOH at-78° to afford stereoselectively methyl 3-exo-acetyl-2-oxabicyclo[3.2.0]heptane-7-endo-carboxylates 12b and 12c, respectively, while a 2:1 diastereoisomeric mixture of methyl 3-acetyl-2-thiabicyclo[3.2.0]heptane-7-endo-carboxylates 13 and 14 is obtained from the corresponding S-derivative 11b. The outcome of the Huang-Minlon reduction of the 1-methyl-substituted ketones 10a and 11a is again influenced by the heteroatom in the tricycle. While 1-methyl-7-oxatricyclo[3.2.1.03,6]-octane (15) is the only product from the corresponding oxatricyclooctanone 10a, a 1:2 mixture of 1-methyl-7-thiatricyclo[3.2.1.03,6]-octane (16) and 3-methylbicyclo[3.1.1]hept-2-ene-6-endo-thiol (17) is obtained from the analogous S-compound 11a, both products stemming from a common carbanion precursor.

Notizen: The reaction of highly alkylated azulenes with dimethyl acetylenedicarboxylate (ADM) in decalin or tetralin at 180-200° yields, beside the expected heptalene- and azulene-1,2-dicarboxylates, tetracyclic compounds of type ‘anti’-V and tricyclic compounds of type E (cf. Schemes 2-4 and 8-11). The compounds of type ‘anti’-V represent Diels-Alder adducts of the primary tricyclic intermediates A with ADM. In some cases, the tricyclic compounds of type E also underwent a consecutive Diels-Alder reaction with ADM to yield the tetracyclic compounds of type ‘anti’- or ‘syn’-VI (cf. Schemes 2 and 8-11). The tricyclic compounds of type E, namely 4 and 8, reversibly rearrange via [1,5]-C shifts to isomeric tricyclic structures (cf. 18 and 19, respectively, in Scheme 6) already at temperatures 〉 50°. Photochemically 4 rearranges to a corresponding tetracyclic compound 20 via a di-π-methane reaction. The observed heptalene- and azulene-1,2-dicarboxylates as well as the tetracyclic compounds of type ‘anti’'-V are formed from the primary tricyclic intermediates A via rearrangement (→heptalenedicarboxylates), retro-Diels-Alder reaction (→ azulenedicarboxylates), and Diels-Alder reaction with ADM. The different reaction channels of A are dependent on the substituents. However, the main reaction channel of A is its retro-Diels-Alder reaction to the starting materials (azulene and ADM). The highly reversible Diels-Alder reaction of ADM to the five-membered ring of the azulenes is HOMO(azulene)/LUMO(ADM)-controlled, in contrast to the at 200° irreversible ADM addition to the seven-membered ring of the azulenes to yield the Diels-Alder products of type E. This competing reaction must occur on grounds of orbital-symmetry conservation under SHOMO(azulene)/LUMO(ADM) control (cf. Schemes 20-22). Several X-ray diffraction analyses of the products were performed (cf. Chapt. 4.1).

Notizen: The synthesis of glycerolipids linked to hydroxamate derivatives designed for two-dimensional crystallization of aminopeptidase M is reported. The lipid moieties are readily obtained using a convergent pathway. Their structure allows the introduction of a wide variety of ligands of biological interest.

Notizen: Tryptimines of type 7 form with various acyl halogenides EX preferentially tricycles of type 8 (cf: Scheme 2). The homochiral imines 9 and 17 are transformed into (2′R,3S)-configurated products. The synthetic and mechanistic importance of these results is discussed.

Notizen: It is shown here that the red seaweed Laurencia microcladia KÜTZNING, collected in the Mediterranean off the torrent Il rogiolo, contains the C15 acetogenin rogioloxepane A ( = (+)-(2R,7R)-2-(1-bromopropyl)-7-[(Z)-1-chlorohex-3-en-5-ynyl]-2,3,6,7-tetrahydrooxepin; (+)-3) besides its epoxy derivative rogioloxepane B ((+)-4) and the rogioloxepane C ((+)-5) derived from (+)-4 by epoxide opening. Co-occurring is an acyclic C15 acetogenin, perrogioloxepane ( = (7R,4Z,9Z,12Z)-6-chloropentadeca-3,9,12-trien-1-yn-7-ol; 9), which exists preferentially in a folded conformation as required to give, by intramolecular cyclization, rogioloxepane A (3TC) in its favored twist-chair form. Molecular-mechanics calculations support this view and help also to assign the relative configurations at the side chains, whereas the configurations at the seven-membered ring are established via NMR spectroscopy and chemical correlations. The absolute configuration is established by Mosher's NMR method applied to the MTPA esters of (+)-5 or 9.

Notizen: The reaction of trans,trans-[WH(CO)2(NO)(PMe3)2] (1) with (pyridin-2-yl)-substituted aldehydes and ketones, (pyridin-2-yl)C(O)R where R = H, Me, Ph, pyridin-2-yl, and with 6-methylpyridine-2-carbaldehyde was studied. In all cases, facile insertion of the C=O bond into the W—H bond was observed, with rapid subsequent extrusionof a coordinated CO ligand affording O,N-bidentate coordinated tungsten alkoxides. Only in case of pyridine-2-carbaldehyde and di(pyridin-2-yl) ketone, the initial n1 O-bonded insertion product could be observed as unstable intemediates by low-temperature NMR.

Notizen: Starting from 3-(benzyloxy)cyclobutane-1,1-dimethanol, 3-thyminyl- and 3-adenylcyclobutane-1,1-dimethanol were synthesized by direct introduction of the heterocycles (Scheme 1). The mono-O-substituted methoxytrityl derivatives were separately converted to octameric phosphodiesters on an aminomethyl-polystyrene carrier by the phosphotriester method. These oligomers of carba-nucleosides were prepared in order to study their annealing behaviour towards ribo- and deoxyribo-nucleic acids as well as their potential for homologous hybridization.

Notizen: Glycosylsulfenyl snf (Glycosylthio) sulfenyl Halides (Halogeno and Halogenothio 1-Thioglycosides, Resp.): Preparation and Reaction with AlkenesThe disulfides 11-17 and 20 were prepared from 7, 9, and 18 via the dithiocarbonates 8, 10, and 19, respectively (Scheme 2). The structure of 11 and of 13 was established by X-ray analysis. Chlorolysis (SO2Cl2) of 11 gave mostly the sulfenyl chloride 24, characterized as the sulfenamide 26, a small amount of 21, characterized as the (glycosylthio)sulfenamide 23, and the glycosyl chloride 27 (Scheme 3). Bromolysis of 11 followed by treatment of the crude with PhNH2 yielded only 28. Chlorolysis of the diglycosyl disulfide 13, however, gave mostly the (glycosylthio)sulfenyl chloride 21 and 27, besides 24. Bromolysis of 13 (→22 and traces of 25) followed by treatment with PhNH2 gave an even higher proportion of 23. Similarly, 20 led to 29 and hence to 30. In solution (CH2Cl2), the sulfenyl chloride 24 decomposes faster than the (thio)sulfenyl chloride 21, and both interconvert. Addition of crude 24 to styrene (-78°) yielded the chloro-sulfide 31 and some 37, both in low yields. The product of the addition of 24 to l-methylcyclohexene was transformed into the triol 32. Silyl ethers of allylic alcohols reacted with 24 only at room temperature, yielding, after desilylation, isomer mixtures 33 and 34, and pure 35. Much higher yields were achieved for the addition of (thio)sulfenyl halides yielding halogeno-disulfides. Good diastereoselctivites were only obtained with 21, its cyclohexylidene-protected analogue, and 22, and this only in the addition to styrene (→36, 37, 38), to (E)-disubstituted alkenes (→46, 48, 49a/b, 50a/b, 53), and to trisubstituted alkenes (→47, 51, 52, 54, 55). Other monosubstituted alkenes (→41-45) and (Z)-hex-2-ene (→49c/d,50c/d) reacted with low diastereoselectivities. Where structurally possible, a stereospecific trans-addition was observed; regioselectivity was observed in the addition to mono- and trisubstituted alkenes and to derivatives of allyl alcohols. The absolute configuration of the 2-chloro-disulfides was either established by X-ray analysis (47a) or determined by transforming (LiAlH4) the chloro-disulfides into known thiiranes (Scheme 5). Thus, 37, 48, and the mixture of 49a/b and 50a/b gave the thiiranes 56, 61, and 64, respectively, in good-to-acceptable yields (Scheme 5). Harsher conditions transformed 56 into the thiols 57 and 58. Similarly, 61 gave 62. The enantiomeric excesses of these thiols were determined by GC analysis of their esters obtained with (-)-camphanoyl chloride. Addition of 21 to {[(E)-hex-2-enyl]oxy}trimethylsilane, followed by LiAlH4 reduction and desilylation, gave the known 66 (63%, e.e. 74%). The diastereoselectivity of the addition of 21 to trans-disubstituted and trisubstituted alkenes is rationalized by assuming a preferred conformation of the (thio)sulfenyl chloride and destabilizing steric interactions with one of the alkene substituents, while the diastereoselectivity of the addition to styrene is explained by postulating a stabilizing interaction between the phenyl ring and the C(1)-S substituent (Fig.4).

Notizen: The syntheses and biological activities of some nitrostyrene derivatives of adenosine 5′-glutarates, a novel class of selective, bi-substrate-type inhibitors of the EGF receptor protein tyrosine kinase with IC50 values around 1 μM. Only marginal inhibition of the tyrosine kinases v-able and c-src and of the serine/threonine kinase PKC was observed. Compounds 8, 9, 11, and 12 - lacking the adenosine moiety - were ten times less active than the most potent derivatives, whereas 17 - lacking the nitrostyryl part - showed no inhibitory activity at all. Most of the compounds showed potent antiproliferative activity against an EGF-dependent mouse keratinocyte cell line.

Notizen: The template reaction of {bis[(S)-2-(aminomethyl)pyrrolidine]}copper(II) with formaldehyde, nitroethane, and base in MeOH yields optically pure {1,7-bis[(S)-pyrrolidin-2-yl]-4-methyl-4-nitro-2,6-diazaheptane}- copper(II) ([Cu((S,S)-mnppm)]2+) in high yield. The same reaction with rac-2-(aminomethyl)pyrrolidine is also described. Preparative details and spectroscopic and electrochemical properties of the CuII complexes and of the free ligands are reported and compared with structural, spectroscopic and electrochemical data of the CuII complex of the unsubstituted parent ligand 1,7-bis[(S)-pyrrolidin-2-yl]-2,6-diazaheptane (ppm). The crystal structure of [Cu(ppm)]Cl ClO4 has been determined by X-ray diffraction methods.

Notizen: In search of new types of semisynthetic derivatives of the natural antibiotic rifamycin S (1), we synthesized 25-O-deacetyl-27,28-didehydro-27-demethoxy-11-deoxo-11,29-epoxy-28, 29-dihydro-21,23-O-isopropyli-denerifamycin S (3). Its X-ray crystal structure shows a new type of ansa-chain with an 11,29-epoxy moiety, the loss of the MeO group on C(27), and the shift of the C=C bond from C(28),C(29) to C(27),C(28). These modifications result in a conformational rearrangement of the whole ansa-chain, nonetheless the overall spatial shape of the molecule is still close to that of most rifamycins. As found in other 11-deoxo-11-hydroxyrifamycin-S derivatives, the chromophore rings of 3 give rise to π-π association in the crystal.

Notizen: One-Electron Redox Reactions of Octaphenyl[4]radialene: Generation and ESR/ENDOR Characterisation of Its Radical Anion and Radical CationThe cyclovoltammograms of octaphenyl[4]radialene in DMF or THF at room temperature disclose each two quasireversible reduction and oxidation potentials at -1.4 V/-1.7 V and +0.7 V/+0.9 V. Accordingly, both the radical anion and the radical cation can be generated: Ph8C8·⊖ by K metal mirror reduction of a [2.2.2]cryptand containing THF solution, and Ph8C8·⊕ by TI3⊕(⊖OOCCF3)3 oxidation in H2CCl2. Their ESR/ENDOR and General Triple spectra differ considerably in the number of resolved 1H couplings (M·⊖: 5 and M·⊕: 3) as well as in their spectral widths (M·⊖: a1H 0.090 to 0.017 mT; M·⊕: a1H 0.066 to 0.023 mT) suggesting different changes in the D2d structure of the neutral molecule on electron uptake or extrusion.

Notizen: A variety of model compounds for the pyrimidinediyl-based rigid-rod polyamide poly[imino-(pyrimidine-2,5-diyl)-imino-tetraphthaloyl] (PPYMT) was prepared, in order to compare their conformations to several model compounds of the related, fully aromatic polymer poly(p-phenyleneterephthalamide) (PPTA). In particular, the structures of N-(2-pyrimidyl)benzamide (PYMB) and its complexed form bis[(N-pyrimidin-2-yl)benzamide]nickel(II) dichloride (NiPYMB) were determined by X-ray diffraction. The molecular packing in these crystals provides us with a model for the possible ‘cross-linking’ of PPYMT fibers. The structures of the trimer model compounds N,N′ -bis(2-pyrimidyl)terephthalamide (PYTA) and N,N′ -bis(benzoyl)-2,5-diaminopyrimidine (BDAP) yield information about the conformation of PPYMT chains and are compared to analogous model compounds of PPTA.

Notizen: The reaction of 2,2-dimethyl-5-(1,2-epoxypropyl)cyclohexanone (7) with t-BuOK in DMSO furnished a small amount of 5-(1-hydroxyprop-2-enyl)-2,2-dimethylcyclohexanone (12) and the 4 unexpected products 13-16 which contain one to three additional C-atoms (Scheme 2). The relative configuration of the major product 1-(4′,4′-dimethyl-2′,3′-dimethylidenecyclohexyl)propane-1,2-diol (15) was shown to be 1RS, 2RS,1′SR via NOE measurements performed on a derivative thereof. A crossover experiment in DMSO/[13C2]DMSO 1:1 as solvent showed that the two additional C-atoms of this product originate from a single molecule of DMSO (Scheme 5). A tentative mechanistic scheme, consistent with all experimental observations, is proposed which involves a [2,3]-sigmatropic rearrangement of an (allylsulfinyl)methanide to a sulfenic acid as one of the key steps (V → 24, Scheme 8). We corroborated part of this hypothetic scheme by taking recourse to a model compound (7-(methylsulfinyl)-p-mentha-1,8-diene (32/33), readily prepared in two steps from perilla alcohol (30)), which reacted as predicted by the proposed mechanism (Schemes 9 and 10).

Notizen: Roemeria refracta DC. (Papaveraceae) of Turkish origin yielded two novel epimeric N-oxides, (-)-(5R, 11S,14R)-reframidine N-oxide ( = (-)-(5R, 11S,14R)-11,12-dihydro-14-methyl-11,5-(iminomethano)-5H -cyclohepta[1, 2-f: 4, 5-f′]bis[1,3]benzodioxole 14-oxide; 1) and (-)-(5R, 11S, 14S)-reframidine N-oxide ( = (-)-(5R, 11S, 14S)-11, 12-dihydro-14-methyl-11, 5-(iminomethano)-5H-cyclohepta[1, 2-f:4, 5-f′]bis[1, 3]benzodioxole 14-oxide; 2). The isolated (-)-roelactamine ( = (-)-11, 12-dihydro-14-methyl-11, 5-(iminomethano)-5H-cyclohepta[1, 2-f:4, 5-f′]bis[1, 3]benzodioxol-15-one, 4) is the first natural isopavinoid incorporating a lactam group. The epimeric (-)-15-(2-oxopropyl)reframidines ( = (-)-1-[11, 12-dihydro-14-methyl-11, 5-(iminomethano)-5H-cyclohepta[1, 2-f:4, 5-f′]bis[1, 3]benzodioxol-15-y1]propan-2-ones; 5/6) and the epimeric (-)-ethyl (reframidin-15-yl)acetates ( = (-)-ethyl [11, 12-dihydro-14-methyl-11, 5-(iminomethano)-5H-cyclohepta[1, 2-f:4, 5-f′]bis[1, 3]benzodioxol-15-y1]acetates; 7/8) are probably artifacts. (±)-Coclaurine (9), (±)-N-methylcoclaurine (10), (-)-roemeridine (11), and N-feruloyltyramine (12) are also isolated from R. refracta together with the previously reported bases. Specific 13C-NMR assignments are reported for the first time for the isopavines.

Notizen: An electrochemical procedure for the preparation of D-3-alkoxy-halogen-2,3-dihydro-6-methyl-2-oxoergolines-I is described.

Notizen: The synthesis of the novel (1′R*,2′S*,3′R*, 4′S*,5′R*)-1-(3′,4′-epxoy-2′, 5′-dihydroxycyclohexyl)-3-methyl-but-2-enone (2), recently isolated from the culture medium of the fungus Eutypa lata, is described.

Notizen: The crystal Structure of [Fe(η6-mesitylene)2](PF6)2 (1) is reported. The Structure is intricately disordered with the Fe-atom occupying an m3m cubic site, but nonetheless the conformation and bonding is confirmed. The structure is discussed in the general context of FeII sandwich complexes.

Notizen: It is shown that in the red seaweed Jaurencia microcladia, collected in the Mediterranean off the torrent Il Rogiolo, the new branched C15 acetogenin rogiolenyne D ( = (+)-(2S,3S,7R))-3-(bromomethyl)-7-[(Z)-1-chlorohexen-3-en-5-nyyl)]-2-ethyl-2,3,6,7-tetrahydrooxepin; (+)--3 co-occurs with the already reported rogiolenyne A ((-)-1) and B ((-)-2a, suggesting the lineage (+)-3→(-)-1(-)-2a,Which is realized here chemically. The relative configurations are established via NMR analysis and chemical transformations as regards the seven-membered ring, while recourse is made to conformational analysis for the side chain. The absolute configuration is established via the Mosher's NMR method applied to the MPTA esters of (-)-2a.

Notizen: The chemical syntheses of the phosphorothioate of (2′-5′)adenylate dimer (see 6a, 6b) and trimer (see 11a, 11b, 12a, 12b) as well as of their 5′-monophosphates (see 15a, 15b, 16a, 16b) using the phosphoramidite method are described. The resulting diastereoisomer mixtures were separated into the pure components by chromatographical means. All synthetic intermediates were characterized by TLC, elemental analysis, and UV and 1H-NMR spectra.

Notizen: The reaction of 9-bromoanthracene (1) with benzenethiol(ate) in tetraglyme proceeds by a SNAr mechanism. The concurrent formation of anthracene is not due to a competing single-electron-transfer pathway involving either benzenethiol or benzenethiolate anion.

Notizen: The conformational properties of four model peptides of the general formula Ac-Tyr-Xaa-Yaa-Zaa-Ala-Lys-Glu-ala-Ala-Glu-Lys-Ala-Zaa-Yaa-Xaa-Lys-NH2 (Xaa-Yaa-Zaa = Ala-Ala-(R)-Asp(2-Me), 1; Ala-Ala-(S)-Asp(2-Me), 2; Ala-Aib-Asp, 3; Ala-Ala-Asp, 4; Asp(2-Me) = 2-methylaspartic acid; Aib = 2-aminoisobutyric acid) were studied by CD spectroscopy in solution, to evaluate the helix-inducing potential of enantiomerically pure 2-methylaspartic acid as a function of its chirality at C(2). At neutral pH and 1°, all peptides exhibit significant helix formation in aqueous solution, the degree of helicity increasing in the order 4 3 ≈ 1. Lowering the pH to 2 results in a dramatic increase in helicity for peptide 1, while the diastereoisomeric peptide 2 now exists in a predominantly unordered conformation. Helix induction by protonated (R)-Asp(2-Me) exceeds Aib-induced helix formation in peptide 3, and the helix content of 1 in aqueous solution at pH 2 is comparable to the degree of helicity in the strongly helix-inducing solvent 2,2,2-trifluoroethanol.

Notizen: The Crystal and Molecular Structures of Two trans -Bis(N,N-dimethylethylenediamine)cobalt(III) Complexes. Estimate of Steric Ligand-Ligand Interactions by a Molecular-Mechanics ModelTwo trans-bis (N,N-dimethylethylenediamine)cobalt(III)m complexes with different axial ligands (SNC-, NO2-) have been synthesized starting from the corresponding CoII-amine species. An X-ray crystal-structure analysis revealed widely differing Co—N bond distances. While for the primary amino groups, as in complexes of unsubstituted bidentate amines, bond distances are close to 196 pm, those for the tertiary amino groups are stretched by ca. 10 pm. The good agreement between the molecular geometry as calculated by a molecular-mechanics model and experimental data suggests that the differences in bond distances must be primarily due to simple steric effects.

Notizen: Ring Transformation of Imidazolidine-2,4-diones ( = Hydantoins) to 4H-Imidazoles in the Reaction with 3-(Dimethylamino)-2,2-dimethyl-2H-azirinesAt ca. 70°, 3-(dimethylamino)-2,2-dimethyl-2H -azirine (1) and 5,5-disubstituted hydantoins 4 in MeCN or i-PrOH give 2-(1-aminoalkyl)-5-(dimethylamino)-4,4-dimethyl-4H -imidazoles 5 in good yield (Scheme 2). These products are decarboxylated 1:1 adducts of 1 and 4. A reaction mechanism is suggested in analogy to the previously reported reactions of 1 and NH-acidic heterocycles containing the CO—NH—CO—NH moiety (Scheme 5). The formation of ureas 6 and 7 can be rationalized by trapping the intermediate isocyanate F by an amine. No reaction is observed between 1 and 1,5,5- or 3,5,5-trisubstituted hydantoins in refluxing MeCN or i-PrOH, but an N-isopropylation of 1,5,5-trimethylhydantoin (8b) occurs in the presence of morpholine (Scheme 3). The reaction of the bis(azirine)dibromozink complex 11 and hydantoines 4 in refluxing MeCN yields zink complexes 12 of the corresponding 2-(1-aminoalkyl)-4H -imidazoles 5 (Scheme 4).

Notizen: A New and Simple Method for the Synthesis of Spirocyclic la-QuinolinesThe reaction of anilines with (+)-(R)-pulegone in toluene at temperatures between 125 and 150° with 4-toluenesulfonic acid or I2 as catalysts leads to diastereoisomeric mixtures of spiro[cyclohexane-1,2′(1′H)-quinoline] derivatives (see 1-4, Scheme 1; Table). The diastereoisomers are separated by column chromatography, and the structure of the single isomers is determined by NMR-spectroscopic methods. A reaction mechanism proceeding via several 6π-electrocyclic rearrangements and H-shifts is proposed for the formation of 1H-quinolines 1-4 (Scheme 2). This mechanism is in accordance with the results of the reaction of 2-isopropenylaniline with 3-methylcyclohexanone which leads to a stereoisomeric mixture of 3,4′-dimethylspiro[cyclohexane-1,2′(1H)-quinolines] (Scheme 3).

Notizen: The reaction of [Re(CO3)L2Cl] (L = (MeI)3P, 1a; L = (i-PrO)3P, 1b; L = (PhO)3P, 1c; L = Me3P, 1d; L = Et3P, 1e) with t-BuLi and phenylacetylene in THF affords bis (phosphorus donor) (dicarbonyl) {η2(C,O)-[(E)-4,4-dimethyl-3-oxo-1-phenylpent-1-3n-2-yl]}rhenium (L = (MeO)3P, 2b; L = (PhO)3P, 2c; L = Me3P, 2d; L = Et3P, 2c). Compounds 2b and 2d were characterized by X-ray structure analysis.

Notizen: 6α,β-Tetrahydro-L-[3′-2H1]biopterin ([3′-2H1]-1) was administered orally to two primapterinuric patients in order to investigate the biosynthetic pathway of 7-substituted pterins in humans. L-Primapterin (2) and L-biopterin were isolated from urine after loading and measured by GC/MS. L-Biopterin and L-primapterin were labelled with 2H to an equal extent. From this result, one can conclude that L-primapterin is formed from tetrahydro-L-biopterin, very probably via an intramolecular rearrangement.

Notizen: Cycloaddition of the allenic acid 3 with the N -cyclohexyl-N′ -heteroaromatic carbodiimides 2a and 2b gave the isomeric pyrido[1,2-a]pyrimidinones 4 and 5 and thiazolo[3,2-a]pyrimidinones 6 and 7, respectively, instead of the expected Diels-Alder adducts analogous to 1. The compounds of the latter type, i.e. 8 and 9, were formed from 3 and carbodiimides 2c and 2d, respectively, containing an N′-(pyrazin-2-yl) or N′-(pyrimidin-2-yl) substituent.

Notizen: The seed oils of I.pseudacorus LINN., I.sibirica LINN., and I.missouriensis NUTTAL. contain appreciable amounts of phenols, quinones, and resorcinols, substituted with homologous alkyl or alkenyl side chains. The structure elucidation of these compounds is described, and their possible biosynthesis is discussed.

Notizen: To demonstrate the neighbouring-group participation of the 2-benzyloxy group in the glycosidation of phenols and of strongly acidic alcohols by the diazirine 1, we examined the glycosidation of 4-nitrophenol, 4-methoxyphenol, (CF3)2CHOH, MeOH, and i-PrOH by the diazirine 11, derived from the 2-deoxypyranose 6. Oxidation of the oximes 7 yielded (E)- and (Z)-8. In solution, (E)-8 isomerised to (Z)-8. Similarly, the (E)-configurated mesylate 9, prepared from 8, underwent acid-catalysed isomerisation to (Z)-9. Treatment of (Z)-9 with NH3, followed by oxidation of the resulting diaziridine 10 with I2, yielded the desired diazirine 11. Glycosidation by 11 of the above mentioned hydroxy compounds yielded the glycosides 12-21. In agreement with the postulated neighbouring-group participation, these glycosidation proceeded without, or with a very low diastereoselectivity, favouring the axial anomers.

Notizen: Isomerization of olefins, in particular the useful transformation of allyl to vinyl ethers is catalyzed by the hexaaquaruthenium(2+) ion, producing the (E)-isomers under mild conditions.

Notizen: Twelve heteroaromatic complexing agents 9a-I were synthesized with the purpose to develop suitable labels for time-resolved luminescence-based bioaffinity assays. The relative luminescence yields, excitation maxima, and emission decay constants of their europium(III) and terbium(III) chelates were determined. According to these results, 2,2′,2″,2‴-[(2,2′-bipyridine-6,6′-diyl)bis(methylenenitrilo)]tetrakis (acetic acid) (9e) and 2,2′,2″,2‴-[(2,2′:6′,2″-terpyridine-6,6″-diyl)bis(methylenenitrilo)] tetrakis(acetic acid) (91) are the most promising agents.

Notizen: Using semiempirical and ab initio procedures, the most stable conformations of meso- and rac-bioxirane and of some substituted 1,2:3,4-diepoxides were calculated. For threo-diepoxides (having the same relative configurations as rac-bioxirane, 3), two stable conformations with CCCC dihedral angles of ca. 90 and ca. 270° were found. For erythro-diepoxides (derivatives of meso-bioxirane, 4) the calculations suggest three preferred conformations with corresponding dihedral CCCC angles of ca. 90°, ca. 180°, and ca. 270°. The calculations are in fair agreement with the experimental data available for the unsubstituted compounds 3 and 4.

Notizen: Two cytotoxic triphenylpyrrolo-oxazinones were isolated from a tunicate and their structures elucidated by spectral methods. Lukianol A ( = 3,7,8-tris(4-hydroxyphenyl)pyrrolo[2,1-c][1,4]oxazin-1 (1H)-one; 1) had MIC of 1 μg/ml in KB cytotoxicity tests; MIC value for 2 was 100 μg/ml.

Notizen: The reaction of FeO+ with toluene in the gas phase occurs at collision rate (kr = 1.36 × 10-9 cm3 molecule-1 s-1), and labeling experiments demonstrate that the total products due to C—H bond activation involve to 〉 92% the benzylic position. In the ‘hydride’ abstraction process (formation of FeOH and C7H7+), the H-atom originates elusively from the benzylic position to generate a benzyl cation, and an intramolecular kinetic isotope effect kH/kD = 1.75 has been obtained. There is no evidence for the existence of isotopically sensitive branching (‘metabolic switching’) in the system studied.