ALBERT

Notizen: Azimines. IITeil I, siehe [1]. . Preparation and Thermal Fragmentation of cis- and trans-2,3-Diphenyl-1-phthalimido-2,3-di[15N]-azimine Teilweise vorgetragen in der Versammlung der Schweizerischen Chemischen Gesellschaft am 8./9. Oktober 1976 in Genf und als Autoreferat veröffentlicht [2].cis- and trans-2,3-Diphenyl-1-phthalimido-2,3-di[15N]-azimine (11 and 12) wer synthesized from cis-di[15N]-azobenzene (10) and phthalimido-nitrene (2), the latter generated by lead tetraacetate oxidation of N-aminophthalimide (1). Useful information was obtained from the comparison of several data of 11 and 12 with those of the unmarked diphenyl-azimines 5 and 6 (R = C6H5).The 15N- and 13C-NMR. spectra of 11 and 12 were interpreted to furnish additional evidence for the azimine structure and for the indicated configurations. The IR. spectra permitted identification of two bands in the 1200 to 1450 cm-1 region, probably characteristic for the functionality of diaryl-phthalimido-azimines. Comparison of the mass spectrum of 11/12 with that of the unmarked analogues 5/6 (R = C6H5) permitted the interpretation of the fragmentation path of 1-phthalimidoazimines. The major path may be the purely thermal decomposition to 13 and 7 (R = C6H5), respectively. Two other competing fragmentation paths are discussed.Prolonged thermolysis of 11 at 61° in solution gave 83% of N,N′-diphenyl-N N′-phthaloyl-di[15N]-hydrazine (13) of 98% isotope purity, which means that the imide nitrogen atom and N(1) of the azimine function are removed in this reaction. A mechanism passing through an intermediate cyclic tetrazene 16 is considered.Benzocyclobutenedione (14) added to trans-azobenzene (4, R = C6H5) under the influence of a high pressure lamp in a quarz apparatus to give N,N′-diphenyl-N,N′-phthaloyl-hydrazine (7, R = C6H5). This reaction was found not to take place in the dark, even after prolonged heating in trichloromethane.

Notizen: Azimines. I. Synthesis and Stereoisomerism of 2, 3-Diaryl- and 2, 3-Dialkyl-1-phthalimido-aziminesTeilweise vorgetragen in der Versammlung der Schweizerischen Chemischen Gesellschaft in Lausanne am 7./8. Mai 1971 und als Autoreferat veröffentlicht [1].Special examples of a new class of compounds, the open-chain azimines (1), have been prepared and their properties examined.Addition of phthalimido-nitrene (4), generated by lead tetraacetate oxidation of N-aminophthalimide (3), to cis- and trans-azobenzene (6 and 5), -azo-p-toluene (8 and 7), and to trans-azomethane (9), -azoethane (10) and -azo-α-phenylethane (11) afforded the separable cis- and trans-isomers of 2, 3-diphenyl- (12 and 13), 2, 3-di-p-toyl- (14 and 15), 2, 3-dimethyl- (16 and 17), 2, 3-diethyl- (18 and 19) and 2, 3-di-(α-phenylethyl)-1-phthalimido-azimines (20 and 21) in different ratios (see Scheme 1).The constitution of the nitrene azo compound adducts as azimines was derived from their properties, especially from the conjugation effect (visible in the UV. spectra) of the aryl-substituted compounds and from the non-equivalence (shown by the 1H-NMR. spectra) of the substituents on the two nitrogen atoms derived from the azo compounds. This evidence excluded the triaziridine 22 and an alternative azimine constitution 23 for the adducts.Of the two stereoisomers obtained for each of the azimines, the aryl-substituted examples 12/13 and 14/15 were readily interconverted by warming in solution, the cis-isomers 12 and 14 exceeding the trans-isomers 13 and 15 in the equilibrium. The dialkyl-azimines appear to be configurationally more stable, since interconversion of the dimethyl-azimines 16 and 17 was not possible under the same conditions, and also not before another thermal reaction took place (see below).The identification of the N(2)-N(3) bond as the stereogenic center, i.e. that the stereoisomerism of the azimines is due to the difference in relative position at N(2) and N(3) of the substituents derived from the azo compounds, as well as a configurational assignment was possible in the aryl-substituted examples on the basis of the UV. spectroscopic comparison of the isomeric azimines with the corresponding stereoisomeric azoxy compounds: The cis-azimines 12 and 14 showed absorptions similar to those of cis-azoxybenzene and cis-azoxy-p-toluene, and the trans-azimines 13 and 15 showed absorptions similar to those of the respective trans-azoxy compounds. With respect to the configuration of the alkyl-substituted azimines, it was observed that the isomers 17 and 19, which from their formation and chromatographic behaviour are likely to be the trans-isomers, show a visible coupling (∽ 1 Hz) between the two H (α)'s in the 1H-NMR. spectrum, whereas the dimethyl isomer 16 (cis) does not exhibit such a coupling.Thermal treatment of four azimines, namely 12, 14, 16 and 17, in solution for a longer time afforded the corresponding N, N′-disubstituted N, N′-phthaloyl-hydrazines 27, 28 and 29. The order of velocity of this fragmentation with nitrogen extrusion was 12/13 ≍ 14/15 〉 16(cis) 〉 17(trans).

Notizen: The 6-chloro-2-cyclohexenones 3, 6 and 11, and the 5-chloro-2-cyclopentenone 15 were newly synthesized. The results obtained with compounds 3 and 15 in photocycloadditions to olefins show that the oxetane vs. cyclobutane product ratio is reduced by the substitution of florine by chlorine in the α′ -position of the enone. No oxetanes are formed in the intramolecular photocycloaddition of 6. Compound 11 does not photoadd to olefins. The newly synthesized 2-chloro-3-cyclohexenones 8 and 9 are also photostable towards light of λ=366 nm, but π-π*-excitation (λ=254 nm) in pentane leads to the formation of 4,4-dimethylcyclohexanone (29).

Notizen: Polynuclear Cobalt Complexes. II. Preparation and Structure of [(tren) (NH3)Co(O2)Co(NH3) (tren)](SCN)4 · 2H2OThe title compound is obtained on oxygenation of [Co(tren)(H2O)2]2+ in 6M aqueous ammonia or by ligand exchange starting from [(NH3)5Co(O2)Co(NH3)5]-(NO3)4. An X-ray structure determination was made. The substance forms monoclinic crystals, space group P21/c, lattice constants a=10,135, b=8,473, c=19,484 Å, β=108,58°, with two formula units in the cell. The final R is 0,066. The binuclear cation has a center of symmetry, so the Co—O—O—Co unit is planar; the Co—O—O angle is 111,5°. The tertiary nitrogen atoms of both chelate groups are cis to the O2 bridge, as found in doubly bridged [(tren)Co(O2,OH)Co(tren)](ClO4)3 · 3H2O.On acidification in solution, the singly bridged cation [(tren) (NH3)CoO2Co(NH3)(tren)]4+ (a) loses the bound O2 completely. But unlike the doubly bridged cation b, the rate of dissociation of a is independent of pH (Fig. 5). At higher pH (8-10) bridging a→b (Fig. 2) occurs. Both reactions must have the same rate determining step, the first order rate constants being of the order of 2 · 10-3 s-1 (25°, 0,35M KCl).

Notizen: Following the intraperitoneal administration of high doses of 14C- and 3H- labelled retinoic acid (1) to rats, three major metabolites and the intact compound were isolated from the feces in microgram amounts by use of column, thin-layer and high-pressure liquid chromatography. Their structures were elucidated by mass spectrometry and Fourier Transform 1H-NMR. spectroscopy as 2 (all-trans-4-oxoretinoic acid), 3 (7-trans-9-cis-11-trans-13-trans-5′-hydroxy-retinoic acid).Hydroxylation of the 5-methyl group of the cyclohexene ring, oxidation of the cyclohexene ring in position 4 and cis-trans isomerisation of the nonatetraenoic acid side chain were the reactions, which produced these products from retinoic acid. The metabolites 2 and 4 each accounted for about 4% of the radioactivity administered. The metabolite 3 and the parent compound accounted for about 16% and 17% of the dose, respectively.

Notizen: Novel types of acetylenic sugarsThe coupling, following Cadiot's procedure, of a 6-bromo-5,6-dideoxy-1,2-O-isopropylidène-3-O-methyl-α-D-xylo-hex-5-yno-1, 4-furanose (1) with phenylacetylene, 2-propyn-1-ol or terminal acetylenic sugars gave with excellent yields the expected diynes (an enediyne when the terminal acetylene was the 3,5, 6-trideoxy-1,2-O-isopropylidene-α-D-glycero-hex-3-en-5-yno-1,4-furanose 7). The chloro analogue 8 of 1 on treatment with lithium thiophenate gave the corresponding phenylthio-acetylenic sugar 9. An acetylene was also formed by reacting the gem-difluoro-olefinic sugar 10 with butyllithium whereas the same olefinic sugar and its 3-O-benzyl analogue 11 gave only a gem-fluoro-arylthio-olefinic sugar (13-15) as a mixture of the Z and E isomers (Z/E 〉 4) when treated with the conjugate base of an arylmercaptan.

Notizen: Some more examples of stable free radicals of carbohydrate heterocyclic derivatives2-Glycosyl-4,4,5,5-tetramethylimidazoline- 3-oxide-1-oxyls and 2-glycosyl-4,4,5,5-tetramethylimidazoline 1-oxyls have been prepared in nine carbohydrate series, which proves the generality of the method. The hyperfine coupling constant between the free electron and the α-proton of the glycosyl group is never very large (0-2.3 G) but a correlation between its value and the structure of the aglycone has been noted. Free radicals of that type, stable in aqueous solutions, are potentially interesting for biological studies.

Notizen: Interpretation of the chemical and spectral (IR., UV., 1H- and 13C-NMR.) properties of the antitumor antibiotic hedamycin (C41H50N2O11) suggests that the molecule contains a methyl substituted 1-hydroxyanthraquinone nucleus, an α, β-unsaturated ketone, two sugar-like tetrahydropyran rings (4 and 8) and an aliphatic chain 2, presumably with an epoxy group (see the Scheme).

Notizen: Halogenated pyridines and 1,8-naphthyridines. VI.The principle of the synthesis of 3-halomethyl-2,6-dichloro-pyridines has been extended to compounds with side chains of more than one carbon atom in the 3-position. Feasible synthetic routes are outlined starting from cheap, commercially available α-methylideneglutaronitrile and trichloroalkyl functional compounds which yield the intermediate 1,3,5-trisubstituted alkanes. These are cyclized by aqueous mineral acid or by hydrogen bromide in an organic solvent to 2-substituted glutarimids or hexahydronaphthyridinones, depending on the mode of cyclization. The final aromatization provides a simple route to pyridines or 1, 8-naphthyridines.

Notizen: Proton catalysed [1,2]-H-shift in the rearrangement of 6,7-diphenyl-5,6-dihydropterine (I) to 6,7-diphenyl-7,8-dihydropterine (III)The arrangement from I to the thermodynamically more stable III undergoes through a acid catalysed [1,2]-H-shift (intramolecular 6,7-hydride rearrangement) (see Scheme 1).

Notizen: Reaktionen von 1,3,5,7-Tetramethyl-anti-tricyclo[5.1.0.03,5]octan-2,6-diolen und deren 4,4,8,8-Tetrachlor- und 4,8-Dichlorderivaten mit DiphosphortetrajodidEs wurden die P2I4-Reaktionen mit 1,3,5,7-Tetramethyl-anti-tricyclo[5.1.0.03,5]-octan-2,6-diolen (3/6), mit dem 4,8-Dichlorderivat 4 und mit den 4,4,8,8-Tetrachlorderivaten 5/7 untersucht. Dabei entstanden die Styrolderivate 9 und 12, die anti-Bishomobenzolderivate 8 und 11, ein Homotropylidenderivat 10, ein Cyclo-octatetraenderivat 13 und ein 9-Oxabicyclo[4.2.1]nona-2,4,7-trienderivat 15. Die Ausbeuten lagen zwischen 1 und 10%. Die Bildung aller dieser Produkte liess sich unter der Annahme der primären Umwandlung einer oder beider Hydroxylgruppen in Abgangsgruppen X oder X und Y (wahrscheinlich X=Y=I) mechanistisch deuten. Die Reaktion der Deschlorderivate 3/6 lieferte nach Substitution beider Hydroxyl-gruppen durch X und Y: (a) unter Abspaltung von HX und HY das Styrolderivat 9 (Schema 2) und (b) unter Abspaltung von XY das Homotropylidenderivat 10 (Schema 3a) und das Bishomobenzolderivat 8 (Schema 3b). Die Reaktion des 4,8-Dichlor-derivates 4 lieferte nach Substitution beider Hydroxylgruppen durch X und Y: (a) unter Abspaltung von HX und HY das Styrolderivat 12 (Schema 2), und (b) unter Abspaltung von XY das Bishomobenzolderivat 11 (Schema 3b). Die Reaktion mit den 4,4,8,8-Tetrachlorderivaten 5/7 lieferte: (a) nach Substitution beider Hydroxyl-gruppen durch X und Y unter Abspaltung von XCl und YCl das Cyclooctatetraen-derivat 13 (Schema 4), und (b) nach Substitution nur einer Hydroxylgruppe durch X unter Abspaltung von XCl und HCl das bicyclische Derivat 15 (Schema 5). Alle diese Reaktionen sind zusätzlich zu den angegebenen Fragmentierungen und Eliminierungen noch teilweise von Umlagerungen des Kohlenstoffgerüstes begleitet.Die thermische Umlagerung von 1,5-Dichlor-2,4,6,8-tetramethyl-cycloocta-1,3,5,7-tetraen (13) in das Styrolderivat 12 wurde in Abhängigkeit der Lösungs-mittelpolarität untersucht und mit der analogen thermischen Umlagerung von Brom-cyclooctatetraen und Chlor-cyclooctatetraen verglichen.

Notizen: Leaf-gland Pigments: Coleons S and T from Plectranthus caninus ROTH (Labiatae), New Hydroquinones of the Abietane Series with a Diosphenol/trans-A/B-6,7-Diketone Structure.Coleons S and T were isolated from the more polar fractions from extracts of the above mentioned plant. Coleon S, C20H26O6, has been shown to have structure 1a, and coleon T, C20H26O6, structure 2.

Notizen: On a Synthesis of the angular Di(cyclobuteno)benzolIn the course of our studies aimed at better understanding the Mills-Nixon effect, we have also prepared the angular di(cyclobuteno)benzene (1), the synthesis of which has been recently described by another group [3]. Our completely different and essentially simpler synthetic approach will be pointed out. A special pyrolysis apparatus is designed.

Notizen: Photochemical reactions of norbornadiene with substituted acetylenes in the presence of Fe(CO)5 gave various products of different types, depending on the nature of the acetylene. The results are summarized in Table 1. The cyclopentanone 1 was always formed in these reactions. In the reaction of disubstituted acetylenes such as dimethyl acetylenedicarboxylate and ethyl phenylpropiolate, the cyclopentenones 2 and 5 were formed, respectively. By contrast, propiolic esters produced the cyclohexenones 3 and 4, in which the ester group was attached on the β carbon with respect to the keto group. Plausible mechanisms for the formation of these products are shown in Schemes 7 and 8. The reaction of diphenylacetylene gave the cyclohexendione 7 as well as the cyclopentenone 6. Two enedione products 8 and 9 were obtained from the reaction of phenylacetylene. Compound 9 was converted to the aromatic diacetate 13 by heating with acetic anhydride in pyridine. On irradiation in the presence of Fe(CO)5 norbornene reacted similarly with dimethyl acetylenedicarboxylate and phenylacetylene to give the cyclopentenone 14 and the cyclohexenone 15, respectively. Compound 15, upon heating, isomerized to hydroquinone 16, which on acetylation gave the diacetate 17.

Notizen: It is shown that the ab initio STO-3G treatment applied to simple saturated linear, branched and cyclic hydrocarbons, assuming standard geometries, yields orbital energies ∊jSTO-3G for their canonical orbital ϕj which correlate perfectly with the observed C2s ionization energies Ijm, if Koopmans' approximation is accepted.Applying the Foster-Boys localization procedure to these canonical orbitals ϕj leads to localized orbitals λμ and their corresponding Hartree-Fock matrix Fλ = (Fλ,μv). An examination of the matrix elements Fλ,μv, i.e. of the self-energies Aμ = Fλ,μμ of the localized CC- and CH-orbitals λμ and of the cross terms Fλ, μv (μ ≠ v) between them, leads to the conclusion that a satisfactory approximation should be obtained by setting Aμ = A for all μ, Fλ,μv = B if λμ and λv are vicinal and neglecting all other cross terms. The resulting model is nothing but the well-known equivalent bond orbital model of Lennard-Jones & Hall, which however can now be calibrated using the known C2s-ionization energies of hydrocarbons. Due to the discrete structure and the wider range (∽ 8 eV) of the C2s band systems in the photoelectron spectra of these molecules this leads to a more satisfactory parametrization than using the narrower and badly resolved C2p band system.Comparison of calculated band positions using the calibrated model with observed C2s-band ionization energies for a series of hydrocarbons reveals that the simple equivalent bond orbital model is better than one might have expected.

Notizen: The Metabolism of the Retinoid Ro 10-9359. Isolation and Identification of the Major Metabolites in Human Plasma, Urine and Feces Synthesis of Three Urinary MetabolitesAfter oral administration of therapeutic doses of the 3H-labelled aromatic retinoic acid analog (retinoid) Ro 10-9359 (ethyl all-trans-9-(4-methoxy-2,3,6-trimethyl-phenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoate) to humans 75 and 15% of the 3H-dose were excreted within the first five days in the feces and the urine, respectively. Using chromatographic procedures including high pressure liquid chromatography 18 metabolites could be isolated from human urine. Their structures were elucidated by mass spectrometry and FT-1H-NMR. spectroscopy. In these urinary metabolites the tetraene side chain of the parent compound Ro 10-9359 is shortened. The radioactivity of the identified urinary metabolites accounted for about 11% of the dose. Three urinary metabolites were synthesized. The main part of the radioactivity excreted within the first five days in the feces consisted of unchanged drug (60% of the dose). A smaller (amount 15% of the dose) could not be identified. The unchanged drug and a major metabolite, the corresponding acid, were found in human plasma.In an experiment with bile-duct cannulated rats the radioactively labelled retinoid Ro 10-9359 was injected intravenously. About 70% of the 3H-dose was excreted in the bile, within the first 48 hours. The whole radioactivity of the rat bile consisted of polar metabolites. No unchanged drug could be found. After enzymatic hydrolysis of the bile conjugates three metabolites were isolated. The main metabolite (49% of the i.v. dose) was a conjugate of the corresponding acid of the parent drug, already found as free compound in human plasma. The other bile metabolites (9 and 7% of the i.v. dose) had an intact side chain, too.An enterohepatic recycling of the bile metabolites was observed in the rat.

Notizen: Stability in aqueous solution of some complexes of heavy metals with diaza-polyoxamacrocyclic ligandsStability of metal complexes (Mn+ = Cu2+, Ni2+, Co2+, Zn2+, Pb2+, Ag+ and Cd2+) with five diaza-polyoxamacrocycles (L = [2.1.1], [2.2.1], [2.2.2], [2.1] and [2.2] ) have been determined at 25°, in 0.1 M Et4N+ClO4- aqueous solutions, by means of potentiometric titrations. All cations form MLn+ complexes; Cu2+ also forms the MHL(n+1)+ protonated species with both [2.2.1] and [2.1.1] ligands. The stability of these complexes has been discussed in terms of structure and by considering the ionic radii of the cations together with the radii of the macrocyclic cavities. Different behaviour is observed between some of these complexes and the well known alkali and alkaline-earth cryptates, partly due to the more covalent nature of bonds formed by the investigated cations and the donor sites of the ligands. The effect of the substitution of two oxygen by two sulfur atoms in the pentadentate ligand [2.1] on the stability of the complexes is reported.

Notizen: An arrangement for light induced vectorial charge separation is discussed in which the electron of the excited dye is transferred to an acceptor and the dye is recovered by electron tunneling through a high and narrow potential barrier. The possible relevance of the model in connection with photosynthesis is considered. Monolayers of Ru(II)-bipyridine complexes with long chain hydrocarbon substituents were investigated which may be useful as component in such arrangements.The surface pressure area isotherms of the monolayers were measured for various ionic compositions of the subphase, and the results demonstrate a strong effect of these ions on the structure of the layers. The layers were deposited on different substrates. The luminescence and its change by contacting the sample with water and by subsequent drying were found to be strongly dependent on the architecture of the layer assembly. Attempts of a photochemical cleavage of water with these assemblies failed.The pH-dependence of the absorption and the luminescence of a Ru(II) bipyridine-dicarboxylic acid complex in solution is interpreted by assuming that the electron in the excited state is localized in one pyridine part of the substituted ligand, the conjugation with the second half of the bipyridine carboxylic acid being negligible. Monolayer assemblies for measuring the energy transfer from the ruthenium complex to an adequate energy acceptor and from an adequate energy donor to the ruthenium complex were investigated. The results demonstrate that the deactivation of the excited ruthenium complex occurs mainly by passing the luminescent state.Assemblies were investigated for measuring the electron transfer from the excited ruthenium complex to an appropriate electron acceptor positioned in the carboxylate portion at the same interface as the electron donor. With bipyridinium ions as acceptor the ruthenium complex luminescence is quenched at average distances between acceptor molecules of about 10 Å, while this distance is 30, 60 und 75 Å for different cyanine dyes used instead of the ruthenium complex. A correlation between this distance and the ionization energy in the excited state of the donor is observed.

Notizen: Synthesis of nickel complexes with a porphine-type ligand systemIn the presence of nickel(II) salts the bicyclic vinylogous amidine 1 is dimerized to the diamagnetic (1-amino-10,20-diaza-octahydroporphinato)nickel(II) complex 3. The condensation proceeds through a paramagnetic octahedral nickel(II) complex 2. Starting from 3, the (hexadecamethyl-10,20-diaza-hexahydroporphin)nickel bis (tetrafluoroborate) 7 (a (hexaaza [16]annulene)nickel(II) complex) was prepared in two steps. This highly electrophilic compound adds methoxide ions in consecutive and reversible steps to form first the (1-methoxy-10,20-diaza-octahydroporphinato)nickel tetrafluoroborate 8 and then the [cis-1, 11-dimethoxy-decahydroporphinato (2-)]nickel 6. 6, 7 and 8 were fully characterized and interconverted by addition and elimination reactions.

Notizen: Singlet oxygen, generated chemically or photogenetically, reacts with biadamantylidene to give the corresponding dioxetane and epoxide only. When methylene blue (MB) or meso-tetraphenylporphin (m-TPP) is used as sensitizer the normal reaction course occurs giving dioxetane as the preponderant product in 2-propanol, ethyl acetate, acetone, pinacolone, methylene chloride, chloroform, carbon tetrachloride and benzene, although in the last two solvents some 10-25% of epoxide is formed. When erythrosin and rose bengal (RB) are used, epoxide becomes the main product (70-95%). Epoxide does not derive from chemical reaction with the solvent. Pinacolone, for example, is not oxidized to t-butyl acetate.The rose bengal reaction involves both singlet oxygen and radicals, since diazabicyclooctane (DABCO) and di-t-butyl-p-cresol interfere with the oxidation. A mechanistic scheme is proposed in which sensitizer and oxygen combine to produce sensitizer radical cation and superoxide radical anion. Subsequently, hydroperoxy radical, deriving from superoxide, reacts with substrate to give epoxide and hydroxy radicals. The latter adds to substrate to give a new radical which captures triplet oxygen. Epoxide is formed by loss of hydroperoxy radical and the chain starts anew. The dioxetane is formed separately either by [2+2]-cycloaddition or stepwise addition.

Notizen: Photochemical and non-photochemical A/D-secocorrin→corrin-cyclizations of 19-carboxy- and 19-formyl-1-methylidene-1,19-secocorrinates. Decarboxylation (and deformylation) of nickel(II)-19-carboxy-(resp. 19-formyl)-corrinatesNickel (II) 1-methylidene-2,2,7,7,12,12-hexamethyl-15-cyano-19-carboxy-1,19-secocorrinate can be induced to cyclize with concomitant decarboxylation to the corresponding corrinate (Scheme 9). Experiments with deuterated derivatives (Scheme 10) indicate that in this decarboxylative A/D-secocorrin→corrin-cyclization the ring closure step precedes decarboxylation. In accord therewith is the finding that the corresponding intermediate nickel(II) 19-carboxy-corrinate (synthesized via photochemical cyclization of the corresponding cadmium complex, Schemes 6 and 9) decarboxylates under very mild conditions.Nickel(II) 1-methylidene-2,2,7,7,12,12-hexamethyl-15-cyano-19-formyl-1,19-secocorrinate cyclizes smoothly to the corresponding 19-formyl-corrinate in the presence of acetic acid/triethylamine. The formyl group of the cyclization product can be eliminated hydrolytically in essentially quantitative yield by treatment with 2N KOH in ethanolic solution (Scheme 11). The non-photochemical (A→D)-cyclization of 19-formyl-1,19-secocorrinoids represents formation of the corrin chromophore at the oxidation level of porphyrinogens and exemplifies how a C1-fragment that eventually leaves the ligand can fulfill a specific function in the (A→D)-ring closure to a corrin.

Notizen: Leaf-gland Pigments: 3β-Acetoxyfuerstione, Nilgherron A and Nilgherron B, New Quinomethanes from Plectranthus nilgherricus BENTH. (Labiatae); Absolute Configuration of FuerstioneWe have isolated from leaf-glands of the above mentioned plant the following deeply coloured quino-methane derivatives: (1) traces of the already known fuerstione (1a); 11,15-dihydroxy-5,7,9 (11), 13-abietatetraen-12-one; (2) the new 3β-acetoxy-fuerstione (1b); (3) nilgherron A (5a, I or II), a new dimeric diterpenoid quinomethane, C40H52O7, formed in the plant obviously by cycloaddition of the o-quinone 8 (9aS, 11R)-11 -hydroxy-2-(1-hydroxy-1-methylethyl-9,9-dimethyl-3,4,7,8,9,9a,10,11- octahydro-5H-dibenzo [a, d]cycloheptene-3,4-dione) with fuerstione; (4) nilgherron B (5b, I or II), C42H54O9, likewise a new compound, formed by the same type of cycloaddition (heterodiene synthesis) of 8 with 3β-acetoxyfuerstione. On the basis of 1H-NMR. shift arguments structure I is slightly preferred to II for 5a and 5b. Model experiments have shown the easy formation of the dihydrodioxin ring by reaction of an o-benzoquinone with p-quinomethanes. The absolute configuration of fuerstione and 3β-acetoxyfuerstione has been determined by chiroptical methods.

Notizen: The bidentate phosphine 2,11-bis(diphenylphosphinomethyl)benzo [c]phenanthrene (1) has been used to prepare the mononuclear, square planar complexes trans-[MX(CO)(1)] and trans-[M(CO)(CH3CN)(1)][BF4] (M = Rh, Ir; X = Cl, Br, I, NCS). It is found that the tendency of these complexes to form adducts with CO, O2 and SO2 is significantly lower than that of the corresponding Ph3P complexes. The oxidative-addition reactions of complexes trans-[IrX (CO) (1)] with hydrogen halides give the six-coordinate species [IrHX2(CO) (1)]. The complexes [IrH2I (CO) (1)] and [IrH2L (CO) (1)] [BF4] (L = CO and CH3CN) have been obtained from hydrogen and the corresponding substrates. The model compounds trans-[MCl (CO) (Ph2PCH2Ph)2] (M = Rh, Ir), trans-[Ir (CO) (CH3CN) (Ph2PCH2Ph)2] [BF4], [IrHCl2(CO)(Ph2PCH2Ph)2] and [IrH2(CO)2(Ph2PCH2Ph)2] [BF4] have been prepared and their special parameters are compared with those of the corresponding complexes of ligand 1. The influence of the static requirements of this ligand on the chemistry of its rhodium and iridium complexes is discussed.

Notizen: The preparation of the ditertiary phosphines 2,11-bis (di-m-tolylphosphinomethyl)benzo [c]phenanthrene (1b), 2,11-bis (di-p-anisylphosphinomethyl)benzo-[c]phenanthrene (1c), 2,11-bis (di-m-trifluoromethylphenylphosphinomethyl) benzo-[c]phenanthrene (1d), 2,11-bis (dicyclohexylphosphinomethyl)benzo [c]phenanthrene (1e) and 2,11-bis [di-(t-butyl)phosphinomethyl]benzo [c]phenanthrene (1f), by a combination of synthetic routes is described.

Notizen: (+)-Pisiferic acid (1), an antibiotic active against Gram-negative and Gram-positive bacteria, was synthesized starting from dehydroabietic acid (2) or abietic acid (26). The terpene ring system was functionalized and a Barton reaction used to oxidize Me(20). The intermediates of this photochemical reaction were isolated and characterized.

Notizen: Oligonucleotides containing 4-aminobenzimidazole 2′-deoxyribofuranoside (1,3-dideaza-2′-deoxyadenosine; c1c3Ad, 1) were synthesized. For this purpose, various NH2-protecting groups were investigated, and the [(9H-fluoren-9-yl)methoxy]carbonyl group was selected for phosphoramidite protection (→ 4c). Apart from the phosphoramidite 3, the phosphonate 2 was prepared. Compound 1 was incorporated in a homooligonuclectide as well as in oligomers containing naturally occurring nucleosides. The Tm values and the thermodynamic data of various duplexes (11 · 10, 17 · 10, 18 · 10) containing 4-aminobenzimidazole were determined. Although d[(c1c3A)20] (11) does not form a Hoogsteen duplex with d(T20) (10) as observed with d[(c1A)20], it destabilizes the Watson-Crick duplexes to a much smaller extent than it was expected from a bulged loop structure. Apparently, 4-aminobenz-imidazole interacts with regular nucleoside residues within a Watson-Crick duplex structure, most likely by vertical stacking. According to the low basicity of the amino group, only weak H-bonding is expected.

Notizen: On the Biosynthesis of γ-Dodecanolactone in Ripening Fruits: Flavor Constituents from Strawberries (Fragaria ananassa) and Peaches (Prunus persica)Administration of deuterium-labelled 9,10-expoxy[8,8-2H2]heptadecanoic acid 8a/b and 9,10-dihydroxy-[8,8-2H2]methylheptadecanoate 9 as lower analogues of oleic acid 1 to ripening fruits of strawberries (Fragaria ananassa) and peaches (Prunus persica) results in the emission of labelled γ-undecanolactone (5) as the lower analog of γ-dodecanolactone (2). The transformation proceeds with loss of a single D-atom from C(8) of the precursors. Early precursors, like the C17-epoxy-acids 8a/b yield (4R)-γ-undecanolactone (5) of high enantiomeric purity, while later intermediates results in (4R)-γ-undecanolactone (5) of low purity. The data support a biosynthetic sequence involving the consecutive action of an epoxide hydrolase and β-oxidation to generate the correct chain length of the lactone percursor. The final steps proceed via cyclization of the 3,4-dihydroxyundecanoic acid 13 to the 3-hydroxy-γ-undecanolactone 14. Elimination of H2O and reduction of the intermediate γ-undec-2-enolactone 15 terminate the biosynthesis of 5. The sequence is representative for the biosynthesis of naturally occurring γ-dodecanolactone (2).

Notizen: Derivatives of fully cross-conjugated tetraethynylethene (3,4-diethynylhex-3-ene-1,5-diyne) 1 are versatile precursors to multinanometer-sized molecular rods with all-C-backbones. Oxidative polymerization (CuCl, N,N,N′,N′-tetramethylethylenthylenediamine (TMEDA), O2) of the trans-bis-deprotected trans-bis(triisopropylsilyl)-protected tetraethynylethene 2 yielded, after end-capping with phenylacetylene, the remarkably stable, soluble oligomers 3-7 with a persilylethynylated poly(triacetylene) (PTA) backbone [—(C≡C—CR=CR—C≡C)n—] and a length of 19.4 (3), 26.8 (4), 34.3 (5), 41.8 (6), and 49.2 (7) Å (Scheme 1). These compounds underwent facile one-electron reductions with the number of reversible reduction steps being equal to the number of tetraethynylethene moieties in each molecular rod. Oxidative Eglinton-Glaser homo-coupling of tetraethynylethenes 8-10 with a single free ethynyl group provided the fully silyl-protected 3,4,9,10-tetraethynyl-substituted dodeca-3,9-diene-1,5,7,11-tetraynes 11-13 (Scheme 2) and, after alkyne deprotection, the novel hydrocarbon 14, a C20H6 isomer, and its partially silyl-protected derivative 15. Oxidative hetero-coupling between two different tetraethynylethene derivatives, one with a single and the other with two free terminal ethynyl groups, yielded the extended chromophores 16-21 composed of 3 or 4 tetraethynylethene moieties (Scheme 3). The linearly conjugated oligomers 16 and 17 with the PTA backbone are isomeric to 19 and 20, respectively, which are members of the cross-conjugated expanded dendralenes, i.e., dendralenes with butadiynediyl fragments inserted between each pair of double bonds [—(C≡C—C(=CR2)—C≡C)n—]. The electronic absorption spectra of these compounds were compared and analyzed in terms of the competition between linear and cross-conjugation in determining the extent of π-electron delocalization. Although steric factors on π-electron conjugation remain to be clarified, this analysis strongly suggests that cross-conjugation is not an efficient mechanism for π-electron delocalization. All extended acetylenic-olefinic chromophores considered in this study exhibited remarkably high stability and did not decompose when exposed to laboratory air and light for months. In agreement with this observation, electrochemical studies demonstrated that the compounds are difficult to oxidize with the oxidation potentials in THF (0.1M(Bu4N)PF6) being higher than 1.0 V (vs. the ferrocene/ferrocenium couple).

Notizen: Optically Active 3-Amino-2H-azirines as Synthons for Enantiomerically Pure αα-Disubstituted α-Amino Acids: Synthesis of the α-Methylphenylalanine Synthons and Some Model PeptidesThe synthesis of a novel 2-benzyl-2-methyl-3-amino-2H-azirine derivative with a chiral amino group is described. Chromatographic separation of the diastereoisomer mixture yielded the pure diastereoisomers 9a and 9b (Scheme 4) which are the D- and L-2-methylphenylalanine ((α-Me)Phe) synthons, respectively. The reaction of 9a and 9b with thiobenzoic acid and with Z-leucine yielded the monothiodiamides 10a and 10b (Scheme 5) and the dipeptide derivatives 11a and 11b (Scheme 6), respectively. Methanolysis of 11b yielded 12b. The absolute configuration of 10a was established by X-ray crystallography. The absolute configuration of (α-Me)Phe in 12b has been deduced from the known configuration of L-leucine.

Notizen: Upon heating in AcOH, the stereoisomeric (Z)- and (R)-6,9-dioxocyclodex-3-enyl derivatives, 5 and 6, respectively, obtained by HgO/I2 oxidation of 5-hydroxy-8-oxo-8,14-seco-5α-androstane-3β,17β-diyl diacetate (3), undergo an unusual intramolecular rearrangement to give the corresponding unsaturated (5R,9R)- and (5R,9S)-spiro-lactones 7 and 8, respectively. Hydroxylation of the C=C bond in 7 and 8, and subsequent glycol cleavage of the resulting diols 9 and 10 afforded the epimeric spiro-lactones (5R,9S)-11 and (5R,9R)-14, respectively, and in both cases, the ring-D-containing fragments 12 and 13.

Notizen: The N′-(glycofuranosylidene)toluene-4-sulfonohydrazides 5 and 10 (Scheme 1) were prepared in good yields by oxidation (1,3-dibromo-5,5-dimethylhydantoin/Et3N) of the N′-glycosyltoluene-4-sulfonohydrazides 4 and 9, which were obtained from 2,3,5-tri-O-benzyl-D-ribose (3) and 2,3,5-tri-O-benzyl-D-arabinose (8), respectively, and toluene-4-sulfonohydrazide. The analogous naphthalene-2-sulfonohydrazides 7 and 12 were similarly prepared from 3 and 8 via 6 and 11. Photolysis in the presence of phenol of the sodium salt 15 (Scheme 2), best generated in situ, yielded the anomeric glycosides 16, some 5, and traces of the glycosides (1R)/(1S)-17. Photolysis of 15 in THF gave the sulfones α-D/β-D-18. Photolysis of 15 (quartz filter) and dimethyl fumarate led to a single cyclopropane 19, the sulfones α-D/β-D-18, and the N-(ribofuranosyl)-N′-(ribofuranosylidene)toluene-4-sulfonohydrazide 20. Similarly, N-phenylmaleimide afforded the cyclopropanes 21 and 22. Photolysis of the sodium salt of 10 and phenol afforded the anomeric glycosides α-D/β-D-23, the C-glycoside 24, and the sulfone 25. Photolytic glycosidation of 15 with N6-benzyladenine gave the two nucleosides 26 and 27 (Scheme 3).

Notizen: First Example of an H-Shift in ‘Thiocarbonyl Aminides’ (N-(Alkylidenesulfonio)aminides)Reaction of benzyl azide (15a) with the sterically hindered C=S group of 4,4-dimethyl-1,3-thiazole-5(4H)-thiones 14 (Scheme 3) and 1,1,3,3-tetramethylindane-2-thione (17, Scheme 4) at 80° leads to the corresponding imines in high yield, without formation of any by-product. In contrast, 15a and 2,2,4,4-tetramethyl-3-thioxocyclobutanone (7) under the same conditions yielded, in addition to imine 19, products 20a and 21 (Scheme 5). For the formation of 20a, a reaction mechanism via [1,4]-H shift in the intermediate ‘thiocarbonyl aminides’ 23 is proposed (Scheme 6). Product 21 as well as the dithiazole derivative 22, which is formed only in the reaction with 4-nitrobenzyl azide (15c), are formal adducts of the dipole 23. Whereas precedents are known for the formation of cycloadducts of type 22, the pathway to 21 is not known. Two possible mechanisms of its formation are proposed in Schemes 8 and 9.

Notizen: Synthetic attempts towards fully conjugated polymers 9 with pentafulvene-diyl structural units are described. Cationic polymerization of pentafulvenes 1a (R = X = Me) and 1b (R = X = MeS) nearly quantitatively gives polymers 8a and 8b with typical Mn and Mw values of 38800 and 53750, respectively, for 8a, and 12000 and 35900, respectively, for 8b. Key step of the conversion 8a → 9a (Scheme 6) is a quantitative bromination 8a → 32a, the structure of 32a being confirmed by analytical data as well as by spectroscopic comparison with model compound 23. Best results in view of two-fold the HBr elimination 32a → 9a are obtained with Et3N, but so far elimination has not been complete. Synthetic sequences are optimized with model compound 21 (Scheme 4). Here again, bromination 21 → 23 is quantitative, while two-fold HBr elimination 23 → 22 with Et3N proceeds in 51% yield. Dibromide 23 easily undergoes HBr elimination followed by a Br shift to give bromide 29. Contrary to cationic polymerization, anionic polymerization of simple pentafulvenes 1 to 2 (which would be attractive in view of the conjugated polymers 3) is not successful: For pentafulvene 1b (R = X = MeS), the main reaction is Diels-Alder-type dimerization 1b → 15b (Scheme 2), even under anionic conditions.

Notizen: Copper(II)-Chloride Catalyzed ‘Carbene Dimerization’ of 1-Halogeno-1-lithiocyclopropanes: A Simple Access to Bi(cyclopropylidenes)A series of 13 bi(cyclopropylidenes) 11 are prepared in a simple one-pot reaction by halogeno-lithio exchange between 1,1-dibromocyclopropanes 1a-n and BuLi, in most cases at -95°, to give 1-bromo-1-lithiocyclopropanes 2a-n, followed by treatment with CuCl2 at low temperature and a simple workup at room temperature (Scheme 3c and Table 1). The yields of bi(cyclopropylidenes) 11 strongly depend on reaction parameters, as explicitly shown for the conversion 1f →→ 11f (Tables 2-8). Mixed couplings between two different carbenoids are possible (Scheme 4), while diastereoselectivity of the active transition-metal complex seems to be low. The structures of bi(cyclopropylidenes) 11 are confirmed by spectroscopic data as well as by X-ray analysis of an isolated crystalline diastereoisomer of 11k (Fig. 1).

Notizen: Several compounds, structurally related to the insect-growth regulator Fenoxycarb (1), were designed and synthesized. These compounds were tested as growth inhibitors of Trypanosoma cruzi cells (epimastigotes). Compounds 6, 16, 18, and 22 were very active against T. cruzi making them promising good candidates either for blood-bank sterilization of Chagas'-disease surveillance, while compounds 11, 12, 13, and 19 showed a moderate degree of activity.

Notizen: The reactions of azetidin-3-ones 6-10, readily available from the amino acids L-alanine, L-phenylalanine, L-valine, L-lysine, and L-aspartic acid, via the corresponding diazo ketones, with nucleophilic reagents such as complex hydrides, Grignard compounds, an ester enolate, and a Wittig ylide give the expected products 11-19 in good yields and mostly in high diastereoselectivities. New amino-alcohol, γ-amino- and γ-amino-β-hydroxy-carboxylic-acid derivatives of known configurations are thus available.

Notizen: Irradiation (λ 〉 390 nm) of 2H-1-benzothiopyran-2-one (1) in the solid state affords selectively 6aα,6bα,12bα,12cα -tetrahydrocyclobuta[1,2-c:4,3-c′]bis[1]benzothiopyran -6,7-dione (2), the head-to-head (HH) cis-cisoid-cis-dimer, while irradiation of 1 in the solid state using shorter wavelengths (λ 〉 340 nm) affords a mixture of all four cis-fused tricyclic dimers 2-5. These results represent a novel wavelength effect in solid-state photochemistry.

Notizen: The synthesis of 7-chloro-, 7-bromo-, and 7-iodo-substituted 7-deaza-2′-deoxyguanosine derivatives 2b-d is described. The regioselective 7-halogenation with N-halogenosuccinimides was accomplished using 7-[2-deoxy-3,5-O-di(2-methylpropanoyl)-β-D-erythro- pentofuranosyl]-2-(formylamino)-4-methoxy-7H-pyrrolo[2,3-d]- pyrimidine (4) as the common precursor. A one-pot reaction (2N aq. NaOH) of the halogenated intermediates 5a-c furnished the desired compounds. Also the 7-hexynyl derivative 2e of 7-deaza-2′-deoxyguanosine is described.

Notizen: The 5-methyl(15N2)[O2,O4-17O2]uridine (= (15N2)[O2,O4-17O 2]ribosylthymine; 15) was synthesized and analyzed by 15N- and 17O-NMR spectroscopy. (15N2)Urea was condensed with 2,3-dibromo-2-methylpropanoyl chloride (3) and cyclized to form (15N2)thymine (5). After glycosidation, the 17O isotopes were introduced in two separate steps: hydrolytic ring opening of 2,5′-anhydro derivative 9 and hydrolysis of 3-nitro-1H-1,2,4-triazole derivative 12 with labelled water in the presence of a strong base. The 15N- and 17O-NMR spectra (Fig.) of 15 in phosphate-buffered water serve as references for heteronuclear NMR spectra of labelled RNA fragments.

Notizen: Hetero-Diels-Alder cycloaddition of acylnitroso dienophile 4 with the N-(butadienyl)pyrrolidinone derivatives 2a, b led with complete regioselectivity to the oxazine adducts 5a, b (Scheme 1). Sequential osmylation, protection of the ensuing glycol, and reduction of the N—O bond gave the expected hemiaminals 11a, b which were characterized by their crystalline sulfite adducts 12a, b (Schemes 1 and 2). Deprotection and saponification of the latter led to aminodeoxyerythrose and to aminodeoxyribose derivatives as an equilibrium of pyrrolidinose equivalents, i.e., hemiaminals 14a, b, imines 14′a, b, and dimers 14″a,b, respectively (Scheme 3). Hydrocyanic acid addition to 11a, b led ultimately to the proline derivatives 16a, b (Scheme 2). Compound 11b proved to be an inhibitor of syncytium formation in AIDS-infected cells.

Notizen: The thermal properties of two ferrocene derivatives, substituted by either one or two cholesteryloxycarbonyl units, were investigated. While the monosubstituted ferrocene derivative 1 was found to be non-mesomorphic, the disubstituted ferrocene derivative 2 exhibited a crystal smectic-B phase. This result shows that ferrocene-containing thermotropic liquid crystals, despite the bulkiness of the metallocene core, are not limited to disordered calamitic phases.

Notizen: NaSMe in toluene leads to regioselective de-C-silylation of the bis[(trimethylsilyl)ethynyl]saccharide 2, but to decomposition of butadiynes such as 1 or 12. We have, therefore, combined the known reagent-controlled, regioselective desilylation of 2 and of 12 (AgNO2/KCN) with a substrate-controlled regioselective de-C-silylation, based on C-silyl groups of different size. This combination was studied with the fully protected 3 which was mono-desilylated to 4 or to 5 (Scheme 1). Triethylsilylation of 5 (→ 6) was followed by removal of the Me3Si group (→ 7), introduction of a (t-Bu)Me2Si group (→ 8) and removal of the Et3Si group yielded 9; these high-yielding transformations proceed with a high degree of selectivity. Iodination of 4 gave 10. The latter was coupled with 5 to the homodimer 11 and the heterodimer 12, which was desilylated to 13. The second building block for the tetramer was obtained by coupling 14 (from 7) with 5, leading to 15 and 16. Removal of the Me3Si group (→ 17) and iodination led to 18 which was coupled with 13 to the homotetramer 20 and the heterotetramer 19 (Scheme 2). Deprotection of 19 gave 21, which was, on the one hand, iodinated to 22, and, on the other hand, protected by the (t-Bu)Me2Si group (→ 23). Removal of the Et3Si group (→ 24) and coupling afforded the homooctamer 26 and the heterooctamer 25. Yields of iodination, silylation, and desilylation were consistently high, while heterocoupling proceeded in only 50-55%. Cleavage of the (i-Pr)3SiC and MeOCH2O groups of 11 (→ 27), 15 (→ 28), 20 (→ 29) and 26 (→ 30) proceeded in high yields (Scheme 3). Complete deprotection in two steps of the heterocoupling products 16 (→ 31 → 32), 19 (→ 33 → 34), and 25 (→ 35 → 36) gave the unprotected dimer 32, tetramer 34, and octamer 36 in high yields (Scheme 4). Only the dimer 32 is soluble in H2O; the 1H-NMR spectra of 32, 34, and 36 in (D6)DMSO (relatively low concentration) show no signs of association.

Notizen: A two-step synthesis of 4-methylcolchicine (13), starting from colchicine (2), has been developed (Scheme 5). In three steps, 4-ethylcolchicine (28) is also accessible from 2 (Scheme 8). Colchicine (2) and its derivatives 13 and 28 have been transformed into the benzo[a]heptalene derivatives 9, 18, and 34, respectively, by Hofmann degradation of the corresponding deacetylcolchiceine 3, 19, and 29, respectively, followed by methylation of the two O-functions first with diazomethane and then with trimethoxonium tetrafluoroborate (Scheme 2 and 6). The thus formed tropylium salts gave, on deprotonation with Me3N in CHCl3, the expected pentamethoxybenzo[a]heptalenes 9, 18, and 34, respectively. X-Ray crystal-structure analysis of 9 (Fig.3) and 18 (Fig. 7), determination of the vicinal coupling constants of the H-atoms at the heptalene skeleton as well as the measurement of the racemization rate of the new benzo[a]heptalenes revealed a marked influence of the substituent at C(4) on the degree of twisting of the heptalene skeleton. The absolute configuration of the resolved heptalenes was deduced from their long-wavelength CD maxima around 350 nm. The heptalenes with a negative maximum in this range possess (7aP)-configuration.

Notizen: The Reaction of 1-Halogeno-1-lithiocyclopropanes with CuCl2: Competition between ‘Carbene Dimerization’ and Oxidative CouplingThe 1-chloro-1-lithiocyclopropanes 2a-d react at low temperature with CuCl2 to give diastereoisomeric mixtures of oxidative-coupling products 5a-d and of ‘carbene dimers’ 6a-d. The relative amount of 5a-d increases with CuCl2 concentration and reaction time. Diastereoselectivity of the reaction seems to be low, and separation as well as spectroscopic structure assignment of single diastereoselectivity of the reaction seems to be low, and separation as well as spectroscopic structure assignment of single diastereoisomers are difficult. The conformational behavior of 1,1′-dichloro-1,1′-bi(cyclopropyls) 5c and 5d is discussed. Contrary to 2a-d, 1-bromo-1-lithiocyclopropanes normally react with CuCl2 to give ‘carbene dimers’ 6 and no coupling products 5. So far the only exception is 1-bromo-1-lithio-2-phenylcyclopropane 2e which in the presence of CuCl2 gives some percents of coupling products 5e besides carbene dimers 6b as main products. An X-ray structure analysis of the predominant diastereoisomer 5e was performed.

Notizen: In contrast to organic reactions, which can almost always be described in terms of a single multiplicity, in organometallic systems, quite often more than one state may be involved. The phenomenon of two states of different multiplicities that determine the minimum-energy pathway of a reaction is classified as two-state reactivity (TSR). As an example, the ion/molecule reactions of ‘bare’ transition-metal-monoxide cations with dihydrogen and hydrocarbons have been analyzed in terms of the corresponding potential-energy hypersurfaces. It turns out that, besides classical factors, such as the barrier heights, the spin-orbit coupling factor is essential, since curve crossing between the high- and low-spin states constitutes a distinct mechanistic step along the reaction coordinates. Thus, TSR may evolve as a new paradigm for describing the chemistry of coordinatively unsaturated transition-metal complexes. This concept may contribute to the understanding of organometallic chemistry in general and for the development of oxidation catalysts in particular.

Notizen: Funicolides A-C (1-3), D (5), and E (7) and 7-epifunicolide A (4), new 5,8(17)-diunsaturated briarane diterpenes, as well as the known analogue brianthein W (6), were isolated from the pennatulacean coral Funiculina quadrangularis (PALLAS, 1766) collected in the Tuscan archipelago. Easy degradation under oxidative and/or basic conditions served to assign the ester groups at C(2) or C(14), while revealing bis-allylic reactivity at C(7) with formation of 16-nortaxane derivatives.

Notizen: 4-Amino-1,5-dihydro-2H-pyrrol-2-ones from Boron Trifluoride Catalyzed Reactions of 3-Amino-2H-azirines with Carboxylic Acid DerivativesReaction of 3-amino-2H-azirines 1 with ethyl 2-nitroacetate (6a) in refluxing MeCN affords 4-amino-1,5-dihydro-2H-pyrrol-2-ones 7 and 3,6-diamino-2,5-dihydropyrazines 8, the dimerization product of 1 (Scheme 2). Thus, 6a reacts with 1 as a CH-acidic compound by C—C bond formation via C-nucleophilic attack of deprotonated 6a onto the amidinium-C-atom of protonated 1 (Scheme 5). The scope of this reaction seems to be rather limited as 1 and 2-substituted 2-nitroacetates do not give any products besides the azirine dimer 8 (see Table 1). Sodium enolates of carboxylic esters and carboxamides 11 react with 1 under BF3 catalysis to give 4-amino-1,5-dihydro-2H-pyrrol-2-ones 12 in 50-80% yield (Scheme 3, Table 2). In an analogous reaction, 3-amino-2H-pyrrole 13 is formed from 1c and the Li-enolate of acetophenone (Scheme 4). A reaction mechanism for the ring enlargement of 1 involving BF3 catalysis is proposed in Scheme 6.

Notizen: In connection with the proposed structure of a trans-membrane cellular ion channel consisting of a complex between poly[(R)-3-hydroxy butanoate] (P(3-HB)) and calcium polyphosphate, CaPPi (ca. 150 units each), which is supposed to contain s-cis-bonds or even more highly strained ester conformations, we have prepared and studied the properties of the cyclic dimer of 3-HB, the diolide 1. All possible forms of 1, the rac-, the meso-, and the enantiomerically pure (R,R)- and (S,S)-compounds were prepared, purified, and characterized. The synthesis (Scheme 1) started from dimethyl succinate with the key step being the Baeyer-Villiger oxidation of the rac- and meso-2,5-dimethylcyclohexane-1,4-diones 5. The rac-diolide 1 was resolved by preparative chromatography on a Chiralcel OD column (Fig.1). The crystal structures of rac- 1 (Fig.3) and of meso- 1 (Fig.5) were determined by X-ray diffraction: the diolides 1 contain s-cis-ester bonds and an ester group with a conformation half way to the transition state of rotation (Fig.2). Strain energies for the diolides 1 of up to 17.8 kcal/mol are suggested. Accordingly, these compounds show reactivities similar to those of carboxylic-acid anhydrides or even acid chlorides. They cannot be chromatographed on silica gel, and they react with primary, secondary, and tertiary alcohols, and with amines to form derivatives of open chain 3-HB ‘dimers’, hydroxy acids 6, esters 7, and amides 8 (Scheme 2). The rate of acid-catalyzed ring opening of the diolides 1 with alcohols has been measured (Fig.6 and 7). From the results described, we conclude that it is unlikely for strained and reactive ester conformations to occur as part of ion channels through phospholipid bilayers of cells.

Notizen: An efficient combination of electrospray mass spectrometry (ES-MS), spectrophotometric and 1H-NMR titrations in solution is used to characterize the assembly of the segmental ligand 2-{6-[1-(3,5-dimethoxybenzyl)-1H-benzimidazol-2-yl]pyridin-2-yl}-1, 1′-dimethyl-5,5′-methylene-2′-(5-methylpyridin-2-yl)bis[1H- benzimidazole] (L2) with ZnII and 4f metal ions, LnIII. Ligand L2 reacts with Zn(ClO4)2 in MeCN to give successively [Zn(L2)2]2+, where the metal ion is coordinated by the tridentate binding units of the ligands, and the double-helical head-to-head complex [Zn2(L2)2]4+. When L2 reacts with Ln(ClO4)3 (Ln = La, Eu, Lu), LaIII only leads to a well-defined cylindrical C1-symmetrical homodinuclear head-to-tail complex [La2(L2)3]6+ in solution, while chemical-exchange processes prevent the 1H-NMR characterization of [Eu2(L2)3]6+, and LuIII gives complicated mixtures of complexes. However, stoichiometric amounts of LnIII (Ln = La, Ce, Pr, Nd, Sm, Eu, Tb, Y, Lu), ZnII, and L2 in a 1:1:3 ratio lead to the selective formation of the C3-symmetrical heterodinuclear complexes [LnZn(L2)3]5+ under thermodynamic control. Detailed NOE studies show that the ligands are wrapped about the C3 axis defined by the metal ions, and the separation of dipolar and contact contributions to the 1H-NMR paramagnetic shifts of the axial complexes [LnZn(L2)3]5+ (Ln = Ce, Pr, Nd, Sm, Eu) in MeCN establishes that ZnII occupies the pseudo-octahedral capping coordination site defined by the three bidentate binding units, while LnIII lies in the resulting ‘facial’ pseudo-tricapped trigonal prismatic site produced by the three remaining tridentate units. Photophysical measurements show that [LnZn(L2)3]5+ (Ln = Eu, Tb) are only weakly luminescent because of quenching processes associated with the C3-cylindrical structure of the complexes. The use of 3d metal ions to control and design isomerically pure ‘facial’ tricapped trigonal prismatic lanthanide building blocks is discussed together with the calculation of a new nephelauxetic parameter associated with heterocyclic N-atoms coordinated to LnIII.

Notizen: Reaction of the tartrate-derived diol (R,R)-α,α,α′,α′-tetraphenyl-2,2-dimethyl-1,3-dioxolane-4,5-dimethanol (TADDOL) with chlorodiphenylphosphane gives a new bis(diphenylphosphanyl) ligand (TADDOP). The complex 4 formed with PdCl2 has been crystallized and its structure determined by X-ray diffraction (Fig.1). The complex is used for Pd-catalyzed enantioselective 1,3-diphenylallylations of various nucleophiles which give products with enantiomer ratios of up to 88:12 (Scheme 2). Crystallization procedures lead to the enantiomerically pure (〉 99:1) product 11 derived from dimethyl malonate. The structure of the TADDOP complex 4 is compared with those of other transition-metal complexes containing chelating bis(diphenylphosphanyl) ligands (Fig.2). A crystallographic data base search reveals that the structures of transition-metal complexes containing two Ph2P groups (superpositions in Fig.3) fall into one of two categories: one with approximate C2 symmetry and the other with C1 symmetry (20 and 19 examples, resp.). A mechanistic model is proposed which correlates the conformational chirality (δ or λ) of the four Ph groups' arrangement in such complexes with the topicity of nucleophile approach on Pd-bound trans,trans-1,3-diphenylallyl groups (Scheme 3 and Table).

Notizen: The regioselectivity of multiple cyclopropanations of C70 with 2-bromopropanedioates in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as base (Bingel reaction) was investigated in a systematic study. Bisadduct formation occurred preferentially at the 6—6 bonds formed by the most pyramidalized sp2-C-atoms at the two opposite poles of the fullerene and, in the reaction with achiral bis[(ethoxycarbonyl)methyl]2-bromopropanedioate (13a), yielded three constitutionally isomeric bis(methano)fullerenes (Scheme 2). Two of them, C2-symmetrical (±)-1 and (±)-2, are chiral; a fact which had not been considered in previous investigations. Formation of the third, C2v-symmetrical isomer 3 was observed for the first time. Configurational descriptions for fullerene derivatives which possess a chiral chromophore as a result of specific functionalization patterns are proposed. Cyclopropanations of C70 with optically active bis[(S)-1-phenylbutyl] 2-bromopropanedioate (13b) yielded five optically active, C2-symmetrical bis-adducts 7-11 which could be separated by preparative HPLC and fully characterized (Scheme 3, Fig.4). Compounds 7/8 and 9/10 represent two constitutionally isomeric pairs of diastereoisomers, and their circular dichroism (CD) spectra show pronounced Cotton effects mainly due to strong chiroptical contributions from the chirally functionalized fullerene chromophores (Fig.7). Since the addition patterns on the fullerene surface in each pair of diastereoisomers have an enantiomeric relationship, their CD spectra closely resemble those expected for two enantiomers. In the third constitutional isomer 11, the addition pattern on the fullerene surface is C2v-symmetrical, and optical activity only results from the chiral addends. Its CD spectrum shows weak Cotton effects mainly from induced circular dichroism originating from the perturbation of the achiral fullerene chromophore by the attached chiral addends. Addition of diethyl 2-bromopropanedioate (2 equiv.) to the C2-symmetrical racemic bis-adduct (±)-2 yielded a mixture of tris-adducts and one major, C2-symmetrical tetrakis-adduct (±)-4 which was isolated in pure form (Scheme 4). Starting from the achiral C2v-symmetrical bis-adduct 3, one single Cs-symmetrical tris-(5) and one C2v-symmetrical tetrakis-adduct (6) were obtained as major products which were isolated and fully characterized (Scheme 5). The regioselectivity for introduction of a second addend in the same hemisphere of C70 is high and resembles the preferred pattern of bis-addition seen in the functionalization of C60.

Notizen: It is shown that strains of the marine ciliate Euplotes raikovi are subtly variable in their production of secondary metabolites. Strains GA8 and 39W from Mediterranean and SB8 from Californian coasts produce the sesquiterpenoid epiraikovenal (3), while strains GA8 and SB8 also produce secoepiraikovenal (4), which play an instrumental niche-exploitation role and have also taxonomic significance. Comparison of 3 and 4 with raikovenal (2) and its putative biogenetic precursor 1, which have similar roles in the conspecific strain Morl from Casablanca coast in the Atlantic Ocean, inspired us the first case of intramolecular tele-dienone-olefin [2+2] photocycloaddition, exemplified here by the transformation of 1 into ent-3. This served also to unequivocally clarify the stereochemical relationship between 3 and 2.

Notizen: The 5′-amino-5′-deoxy-2′,3′-O-isopropylideneadenosine (4) was obtained in pure form from 2′,3′-O-isopropylideneadenosine (1), without isolation of intermediates 2 and 3. The 2-(4-nitrophenyl)ethoxycarbonyl group was used for protection of the NH2 functions of 4 (→7). The selective introduction of the palmitoyl (= hexadecanoyl) group into the 5′-N-position of 4 was achieved by its treatment with palmitoyl chloride in MeCN in the presence of Et3N (→5). The 3′-O-silyl derivatives 11 and 14 were isolated by column chromatography after treatment of the 2′,3′-O-deprotected compounds 8 and 9, respectively, with (tert-butyl)dimethylsilyl chloride and 1H-imidazole in pyridine. The corresponding phosphoramidites 16 and 17 were synthesized from nucleosides 11 and 14, respectively, and (cyanoethoxy)bis(diisopropylamino)phosphane in CH2Cl2. The trimeric (2′-5′)-linked adenylates 25 and 26 having the 5′-amino-5′-deoxyadenosine and 5′-deoxy-5′-(palmitoylamino)adenosine residue, respectively, at the 5′-end were prepared by the phosphoramidite method. Similarly, the corresponding 5′-amino derivatives 27 and 28 carrying the 9-[(2-hydroxyethoxy)methyl]adenine residue at the 2′-terminus, were obtained. The newly synthesized compounds were characterized by physical means. The synthesized trimers 25-28 were 3-, 15-, 25-, and 34-fold, respectively, more stable towards phosphodiesterase from Crotalus durissus than the trimer (2′-5′)ApApA.

Notizen: The 1′,2′-unsaturated 2′,3′-secoadenosine and 2′,3′-secouridine analogues were synthesized by the regioselective elimination of the corresponding 2′,3′-ditosylates, 2 and 18, respectively, under basic conditions. The observed regioselectivity may be explained by the higher acidity and, hence, preferential elimination of the anomeric H-C(1′) in comparison to H—C(4′). The retained (tol-4-yl)sulfonyloxy group at C(3′) of 3 allowed the preparation of the 3′-azido, 3′-chloro, and 3′-hydroxy derivatives 5-7 by nucleophilic substitution. ZnBr2 in dry CH2Cl2 was found to be successful in the removal (85%) of the trityl group without any cleavage of the acid-sensitive, ketene-derived N,O-ketal function. In the uridine series, base-promoted regioselective elimination (→19), nucleophilic displacement of the tosyl group by azide (→20), and debenzylation of the protected N(3)-imide function gave 1′,2′-unsaturated 5′-O-trityl-3′-azido-secouridine derivative 21. The same compound was also obtained by the elimination performed on 2,2′-anhydro-3′-azido-3′-azido-3′-deoxy-5′-O-2′,3′-secouridine (22) that reacted with KO(t-Bu) under opening of the oxazole ring and double-bond formation at C(1′).

Notizen: An eight-step synthetic sequence led from the known D-xylo-pentodialdose 8 to imidazo-L-xylo-piperidinose 15, the key steps being the build-up of imidazole compound 12 by a van Leusen methodology and the intramolecular SN2 ring closure of the O-triflated benzylidene derivative 13. xylo-Piperidinose 15 appears in a half-chair conformation like the oxocarbonium ions which are the postulated intermediates in the glycoprocessing of the pyranose polysaccharides. This bicyclic azasugar should be a glycosidase inhibitor.

Notizen: In 10 steps, 3′,4′-diethynyl-2′,3′,5′-trideoxy-5′-noruridine (14) was synthesized in 5% overall yield from commercial uridine, using conventional methods of nucleoside chemistry. As two functional groups capable to react with each other are present in the same molecule, the synthetic compound is able to form polymers, similar to the polynucleotides, by an acetylene coupling reaction.

Notizen: The synthesis of spiropyrans 11 and 12 and spirooxazines 13-17 containing a thiophene moiety is described. Two different synthetic approaches were used. The spectrokinetic properties of these new compounds are reported.

Notizen: A conformational analysis of the (3′S,5′R)-2′-deoxy-3′,5′-ethano-α-D-ribonucleosides (a-D-bicyclodeoxynucleosides) based on the X-ray analysis of N4-benzoyl-α-D-(bicyclodeoxycytidine) 6 and on 1H-NMR analysis of the α-D-bicyclodeoxynucleoside derivatives 1-7 reveals a rigid sugar structure with the furanose units in the l′-exo/2′-endo conformation and the secondary OH groups on the carbocyclic ring in the pseudoequatorial orientation. Oligonucleotides consisting of α-D-bicyclothymidine and α-D-bicyclodeoxyadenosine were successfully synthesized from the corresponding nucleosides by phosphoramidite methodology on a DNA synthesizer. An evaluation of their pairing properties with complementary natural RNA and DNA by means of UV/melting curves and CD spectroscopy show the following characteristics: i) α-bcd(A10) and α-bcd(T10) (α = short form of α-D)efficiently form complexes with complementary natural DNA and RNA. The stability of these hybrids is comparable or slightly lower as those with natural β-d(A10) or β-d(T10)( β = short form ofβ-D). ii) The strand orientation in α-bicyclo-DNA/β-DNA duplexes is parallel as was deduced from UV/melting curves of decamers with nonsymmetric base sequences. iii) CD Spectroscopy shows significant structural differences between α-bicyclo-DNA/β-DNA duplexes compared to α-DNA/β-DNA duplexes. Furthermore, α-bicyclo-DNA is ca. 100-fold more resistant to the enzyme snake-venom phosphodiesterase with respect to β-DNA and about equally resistant as α-DNA.

Notizen: The course of the thermocatalytic rearrangement of cycloprop-2-ene-1-carboxylates in the presence of dirhodium(II) tetrakis(perfluorobutyrate) ([Rh2(pfb)4]) was investigated by varying the substituents of the cyclopropene ring. Product composition is markedly influenced by the number, nature, and position of the substituents, which determine the regio- and stereoselectivity of the cyclopropene-ring cleavage. A mechanism is proposed in which attack of the electrophilic RhII species is concerted with disrotatory ring opening of the incipient cyclopropyl cation and affords a metal-complexed vinylcarbene. The chemoselectivity of the latter is consistent with that of other carbenes generated in the presence of [Rh2(pfb)4].

Notizen: Under the co-operative influence of two prosthetic groups, and independent of the TiCl4 concentration, complete and constant diastereofacial π-selection was achieved during the [4 + 2] cycloaddition of cyclopentadiene to N,N′-fumaroyl-di[(2R)-bornane-10,2-sultam] ((-)-1c); reactive conformations are discussed.

Notizen: The β-dienoate (+)-(5S)-13a (86% ee; meaning of α and β as in α- and β-irone, resp.) was obtained from (-)-(5S)-9a via acid-catalyzed dehydration of the diastereoisomer mixture of allylic tertiary alcohols (+)-(1S,5S)-15/(+)-(1R,5S)-15 (Scheme 3). Prolonged treatment gave clean isomerization via a [1,5]-H shift to the α-isomer (-)-(R)-16a with only slight racemization (76% ee; Scheme 4). In contrast, the SnCl4-catalyzed stereospecific cyclization of (+)-(Z)-6 to (-)-trans-8a (Scheme 2), followed by a diastereoselective epoxidation to (+)-11 gave, via acid-catalyzed dehydration of the intermediate allylic secondary alcohol (-)-12, the same ester (+)-13a (Scheme 3), but with poor optical purity (13% ee), due to an initial rapid [1,2]-H shift. The absolute configuration of (-)-16a-c was confirmed by chemical correlation with (-)-trans-19 (Scheme 4). 13C-NMR Assignments and absolute configurations of the intermediate esters, acids, aldehydes, and alcohols are presented.

Notizen: The Diels-Alder adduct of 2,4-dimethylfuran to 1-cyanovinyl (1′R)-camphanate ((+)-(1R,2S,4R)-2-exo-cyano-1,5-dimethyl-7-oxabicyclo[2.2.1]hept-5-en-2-endo-yl (1′R)-camphanate ((+)-1)) was converted into (+)-2,7-dideoxy-2,4-di-C-methyl-L-glycero- ((+)-6) and -D-glycero-L-altro-heptono-1,4-lactone ((+)-7), into (-)-(3R,4R,5R,6S)-3,4:5,7-bis(isopropylidenedioxy)-4,6-dimethylheptan-2-one ((-)-22), and into (+)-(2R,3R,4R,5S,6S)-3,4:5,6-bis(isopropylidenedioxy)-2,4-dimethylheptanal ((+)-34). Condensation of ((+)-34 with the lithium enolate of (-)-(1R,4R,5S,6R)-6-exo-[(tert-butyl)dimethylsilyloxy]-1,5-endo-dimethyl-7-oxabicyclo[2.2.1] heptan-2-one ((-)-38; derived from (+)-1) gave a 3:2 mixture of aldols (+)-39 and (+)-40 (mismatched pairs of a α-methyl-substituted aldehyde and (E)-enolate) whereas the reaction of (±)-34 with (±)-38 gave a 10:1 mixture of aldols (±)-41 and (±)-39. A single aldol, (-)-44, was obtained to condensing (+)-34 with the lithium enolate of (+)-(1S,4S,5S,6S)-5-exo-(benzyloxy)-1,5-endo-dimethyl-7-oxabicyclo[2.2.1]heptan-2-one ((+)-43; derived from (-)-(1S,2R,4S)-2-exo-cyano-1,5-dimethyl-7-oxabicyclo[2.2.1]hept-5-en-2-endo-yl (1′S)-camphanate ((-)-3)). All these cross-aldolisations are highly exo-face selective for the bicyclic ketones. The best stereochemical matching is obtained when the lithium enolates and α-methyl-substituted aldehydes can realize a ‘chelated transition state’ that obeys the Cram and Felkin-Anh models (steric effects). Polypropionate fragments containing eleven contiguous stereogenic centres and tertiary-alcohol moieties are thus prepared with high stereoselectivity in a convergent fashion. The chiral auxiliaries ((1R)- and (1S)-camphanic acid) are recovered at the beginning of the syntheses.

Notizen: The Diels-Alder adduct (±)-3 of 2,4-dimethylfuran and 1-cyanovinyl acetate was converted stereoselectively into benzyl 6-(4-chlorophenylsulfonyl)-1,3-exo,5-trimethyl-7-oxabicyclo[2.2.1]hept-5-en-2-exo-yl (26) and -2-endo-yl ether (36). Addition of LiAlH4 to the latter led to the 3-O-benzyl derivatives 28 and 37 of (1RS,2SR,3SR,6SR)- and (1RS,2SR,3RS,6SR)-5-(4-chlorophenylsulfonyl)-2,4,6-trimethylcyclohex-4-ene-1,3-diol, respectively. Methylenation of 6-exo-(4-chlorophenylthio)-1-methyl-5-methylidene-7-oxabicyclo[2.2.1]heptan-2-one (16), obtained by reaction of (±)-3 with 4-Cl-C6H4SCl and saponification gave, 6-exo-(4-chlorophenylthio)-1-methyl-3,5-dimethylidene-7-oxabicyclo [2.2.1]heptan-2-one (43), the reduction of which with K-Selectride afforded 6-exo-(4-chlorophenylthio)-1,3-endo-dimethyl-5-methylidene-7-oxabicyclo[2.2.1]heptan-2-endo-ol (44). The 3-O-benzyl derivative 48 of (1RS,2RS,3RS,6SR)-5-(4-chlorophenylsulfonyl)- 2,4,6-trimethylcyclohex-4-ene-1,3-diol was derived from 44 via based-induced oxa-ring opening of benzyl 6-endo-(4-chlorophenylsulfonyl)-1,3-endo-5-endo-trimethyl-7-oxabicyclo[2.2.1]hept-2-endo-yl ether (49). Benzylation of 28, followed by reductive desulfonylation and oxidative cleavage of the cyclohexene moiety afforded (2RS,3SR,4RS,5RS)-3,5-bis(benzyloxy)-2,4-dimethyl-6-oxoheptanal (32).

Notizen: A series of tetra-N-alkylated 1,4,8,11-tetraazacyclotetradecanes have been synthesized and their complexation potential towards Ni2+ and Cu2+ studied. In the case of sterically demanding alkyl substituents, such as i-Pr, PhCH2, or 2-MeC6H4CH2, no metal complexes are formed, whereas for substituents such as Me, Et, and Pr, the metal ion is incorporated into the macrocycle. The spectroscopic properties of the Ni2+ and Cu2+ complexes in aqueous solution indicate that, depending on the sterical hindrance of the N-substituents, the complexes are either square planar or pentacoordinated. All these Ni2+ and Cu2+ complexes react with N3- to give ternary species, the stability of which have been determined by spectrophotometric titrations. The tendency to bind N3- decreases with increasing steric hindrance of the alkyl substituents. The X-ray studies of the Ni2+ complex with the macrocycle 11, substituted by two Me and two Pr groups, and that of the Cu2+ complex with the tetraethyl derivative 8 show that in the solid state, the metal ions exhibit square planar coordination with a small distortion towards tetrahedral geometry.

Notizen: The title compounds 6 and 7 have been prepared from the known 2,3-di-O-benzyl-4,6-O-benzylidene-D-galactose (18) and N2-acetyl-tri-O-benzyl-D-glucosamine oxime (29) in eight and six steps, respectively. The azidonitrile leading to the benzylated galacto-tetrazole 16 was prepared from 14 and cyclized under the conditions of its formation (Scheme 1). The alcohol 13 was obtained by oxidation of 10 followed by reduction. Better yields and diastereoselectivities were realized, when the benzylidene-protected D-galacto-alcohol 20 was subjected to oxido-reduction, yielding the L-altro-alcohol 22 via the ketone 21 (Scheme 2). Treatment of the corresponding tosylate 24 with NaN3 yielded the tetrazole 25, which was deprotected to 6. The tetrabenzyl ether 16 (from 14, or from 25 via 27) was reduced to 28 and deprotected to give the known deoxygalactostain 8 (Scheme 2). Oxidation of the hydroxynitrile 30, derived from 29, followed by reduction of 32 yielded mostly the L-ido-hydroxynitrile (Scheme 3), which was tosylated and treated with NaN3 to give the tetrazole 35a and its manno-isomer 36a, while Al(N3)3 yielded (E)- and (Z)-38 (Scheme 4). The intermediate azide 39 was isolated besides 40 when NH4N3/DMF was used; thermolysis of 39 gave mostly 35a, which was deprotected to 7, besides some elimination product 41. Both 6 and 7 are stable in the pH range 1-10; at pH 12, 6 is unaffected but, 7 shows some epimerization to the manno-configurated isomer 43. The tetrazole 6 is a competitive inhibitor of the β-galactosidases from E. coli (K1 = 1 μM, pH 6.8) and bovine liver (K1 = 0.8 μM, pH 7.0); the N-acetyl-β-D-glucosaminidase from bovine kidney is competitively inhibited by 7 (K1 ≊ 0.2 μM, pH 4.1).

Notizen: (R)-and (S)-γ-cyclogeranic acid ((R)-and (S)-9, resp.) were obtained by resolution of the racemate, and their absolute configurations determined by chemical correlation. The γ-acids (R)-and (S)-9 were converted into (R)-and (S)-methyl γ-cyclogeranate ((R)-and (S)-6, resp.), and (R)-and (S)-γ-damascone ((R)-and (S)-5, resp.). A more direct entry to (R)-and (S)-9 consisted in the enantioselective protonation of a thiol ester enolate with (-)- or (γ)-N-isopropylephedrine((-)- or (γ)-20) and subsequent hydrolysis of the (R)-and (S)-S-phenyl γ-thiocyclogeranate ((R)- and (S)-24, resp.; 97% ee). The esters (R)- and (S)-24 were also used as precursors of (R)- and (S)-γ-damascone ((R)- and (S)-5, resp.). Alternatively, (S)-5 (75% ee) was obtained by enantioselective protonation of ketone enolate 29 with (-)-N-isopropylephedrine ((-)-20). Organoleptic evaluation demonstrated that the (S)-enantiomers of methyl γ-cyclogeranate and γ-damascone are markedly superior to their (R)-enantiomers.

Notizen: The microscopic ionization behavior of piroxicam was investigated using two different approaches, i.e., direct UV spectroscopy and an indirect analogue approach (deductive method). The best microscopic pKa values (pKa12 = 4.60, pKa21 = 5.40, pKa22 = 2.72, and pKa11 = 1.92) were obtained by the deductive method using as pKa22 the pKa of the enolic O-methylated piroxicam 2. The results show remarkable electrostatic effects in the protonation/deprotonation equilibria, a marked increase in the acidity of the enolic function (2.68 pKa units) being caused by the pyridinium group. The electronic structure of piroxicam was studied based on 1H-NMR chemical shifts at various ionization states, indicating an extended electron conjugation through the molecule. The partition measurements in octan-1-ol/H2O of zwitterionic compound 3 (the pyridyl N-methyl derivative of piroxicam (1)) suggest that the two opposite charges in zwitterionic piroxicam are indeed in a close intramolecular proximity.

Notizen: The synthesis of the trisaccharide β-D-Galp-(1→3)-β-D-GalpNAc-(1→3)-α-D-Galp-1-OPr (2) and of the tetrasaccharide α-L-Fucp-(1→2)-β-D-GalpNAc-(1→3)-β-D-Galp-1-OPr (3), starting from the disaccharidic dihydrooxazole donor 5, is described. Glycosylation of 5 with 6 in the presence of Me3SiOTf gave the trisaccharide 7 which was deprotected with standard methods to give, via 8, compound 2 (Scheme 1). Alternatively, protection of 8 as the 4′,6′-O-benzylidene derivative 9 followed by glycosylation with 10 and by standard deprotection afforded the tetrasaccharide 3 (Scheme 2). Biological testing showed that trisaccharide 2 is unable to inhibit the binding of the monoclonal antibody MBr1 to the target tumor cells MCF7, while tetrasaccharide 3 inhibits the binding in ca. 7-fold extent with respect to the previously tested trisaccharide α-L-Fucp-(1→2)-β-D-Galp-(1→3)-β-D-GalpNAc-1-OPr. These results indicate that the galactose corresponding to the unit D of compound 1 plays an important role in defining the MBr1-recognized epitope and confirm the essential role of fucose for MAb recognition.

Notizen: Two pairs of enantiomerically pure cis-fused cyclopenteno-1,2,4-trioxanes (7, ent-7 and 8, ent-8) are prepared (Schemes 1-3). Their identities are established by dye-sensitized photo-oxygenation of ent-7 and 8, ent-8 to the allylichydroperxides, reduction to the corresponding alcohols, and conversion to the (1S)-camphanates (Scheme 4), the structures of which are determined by X-ray analysis. The dynamic properties of ent-7 are investigated by NMR spectroscopy and PM3 calculations. Evidence for an easily accessible twist-boat conformation is obtained. The in vitro and in vivo antimalarial activities of 7, ent-7,8, and ent-8 as well as those of the racemic mixtures are evaluated against Plasmodium falciparum, P. berghei, and P. yoelii. No correlation is observed between configuration and activity. Racemates and pure enantiomers have commensurate activities. The mode of action on the intraerythrocytic parasite is rationalized in terms of close docking by the twist-boat conformer of the trioxane on the surface of a molecule of heme, single-electron transfer to the O—O σ* orbital, and scission to the acetal radical which then irreversibly isomerizes to a C-centered radical, the ultimate lethal agent (Scheme 5).

Notizen: An efficient synthesis of enantiomerically pure (R)- and (S)-2-(aminomethyl)alanine ((R)- and (S)-Ama) 1a and (R)- and (S)-2-(aminomethyl)leucine ((R)- and (S)-Aml) 1b is described (Schemes 1 and 2). Resolution of the racemic amino acids was achieved using L-phenylalanine cyclohexylamide (2) as chiral auxiliary. The free amino acids 1a, b were converted to the Nα-Boc,Nγ-Z-protected derivatives 11a, b (Scheme 3) ready for incorporation into peptides. Based on the three crystal structures of the diastereoisomeric peptides 8a, 8b, and 9b, the absolute configurations in both series were determined. β-Turn type-I geometries were observed for structures 8b and 9b, whereas 8a crystallized in an extended backbone conformation.

Notizen: The absolute configuration of a series of naturally occurring and semi-synthetic halogenated furanones is proposed on the basis of chemical interconversions and X-ray and CD analyses. The CD analyses clearly reveal that the presence of the allylic O-atom has a strong influence in determining the sign and intensity of the low energy π→π* transition.

Notizen: Benz[a]azulene (1) is synthesized in five steps (cf. Scheme 2) starting from commercially available 2-iodobenzyl alcohol (4) and tropylium tetrafluoroborate in an overall yield of 44%. The key step (cf. also Scheme 1) is the intramolecular Heck reaction of the 8-phenylsulfonyl-substituted heptafulvene 7, which leads in nearly quantitative yield directly to 10-(phenylsulfonyl)benz[a]azulene (8). The desulfonylation of 8 can be accomplished by Julia's method with Na2S2O4/NaHCO3 in DMF/H2O at 85-90°, thus leading to pure 1 in 78% yield. The phenylation of 8 with PhLi or PhCul at -78° in THF occurs regioselectively at C(9). Dehydrogenation of the formed dihydroazulenes with o-chloroanil in toluene at room temperature gives 9-phenyl-10-(phenylsulfonyl)-benz[a]azulene (9) in 70% yield (cf. Scheme 3), which, again, can be desulfonylated with Na2S2O4/NaHCO3 in DMF/H2O in good yields. The addition of PhLi to 1 in THF occurs at temperatures ≥ -25°. Ionic dehydrogenation (1. Ph3C+BF4-/MeCN; 2. Et3N) of the dihydro forms leads to 3, as the main product, and its positional isomers.

Notizen: Dialkynes of the type 3 (Scheme 1) are regioselectively deprotected by treating them either with base in a protic solvent (→4), or- after exposing the OH group- by catalytic amounts of base in an aprotic solvent (→5 and 8). The Me3Si-protected 12 (Scheme 2) is inert to catalytic BuLi/THF which transformed 11 into 9, while K2CO3/MeOH transformed both 10 into 9, and 12 into 13, evidencing the requirement for a more hindered (hydroxypropyl)silyl substituent. C-Silylation of the carbanions derived from 17-19 (Scheme 3) with 15 led to 20-22, but only 22 was obtained in reasonable yields. The key intermediate 27 was, therefore, prepared by a retro-Brook rearrangement of 23, made by silylating the hydroxysulfide 16 with 15. The OH group of 27 was protected to yield the {[dimethyl(oxy)propyl]dimethylsilyl}acetylenes (DOPSA's) 21, 28, and 29. The orthogonally protected acetylenes 20-22, 28, and 29 were de-trimethylsilylated to the new monoprotected acetylene synthons 30-34. The scope of the orthogonal protection was checked by regioselective deprotection of the dialkynes 39-42 (Scheme 4), prepared by alkylation of 35 (→39), or by Pd0/CuI-catalyzed cross-coupling with 36-38 (→40-42). The cross-coupling depended upon the solvent and proceeded best in N,N,N′,N′ -teramethylethylenediamine (TMEDA). Main by-product was the dimer 43. On the one hand, K2CO3/MeOH removed the Me3Si group and transformed 39-42 into the monoprotected 44-47; catalytic BuLi/THF, on the other hand, transformed the alcohols 48-51, obtained by hydrolysis of 39-42, into the monoprotected dialkynes 52-55, all steps proceeding in high yields. Addition of the protected DOPSA groups to the lactones 56 (→57-59) and 62 (→63) (Schemes 5 and 6) gave the corresponding hemiketals. Reductive dehydroxylation of 57 and 58 failed; but similar treatment of 59 yielded the alcohol 61. Similarly, 63 was transformed into 64 which was protected as the tetrahydropyranyl (Thp) ether 65. In an optimized procedure, 62 was treated sequentially with lithiated 31, BuLi, and Me3SiCl (→66), followed by desilyloxylation to yield 60% of 67, which was protected as the Thp ether 68. Under basic, protic conditions, 68 yielded the monoprotected bisacetylene 69; under basic, aprotic conditions, 67 led to the monoprotected bisacetylene 70. These procedures are compatible with the butadiynediyl function. The butadiyne 73 was prepared by cross-coupling the alkyne 69 and the iodoalkyne 71 (obtained from 70, together with the triiodide 72) and either transformed to the monosilylated 76 or, via 77, to the monosilylated 78. Formation of the homodimers 74 and 75 was greatly reduced by optimizing the conditions of cross-coupling of alkynes.

Notizen: Isolation of (-)-dunnione from the leaves of Calceolaria integrifolia, MURR. (fam. Scrophulariaceae)From the leaves of Calceolaria integrifolia, a plant often used in horticulture. partially racemic (-)-dunnione (1) has been isolated. This seems to be the first record of its occurrence outside the family Gesneriaceae, where it previously has been found in two species as the (+)-enantiomer.

Notizen: A chiral economic synthesis of (R)- and (S)-muscone using the cyclofragmentation of epoxysulfonesStarting with isobutyric acid (2) and using a microbiological oxidation with pseudomonas putida (S)-β-hydroxy-iso-butyric acid (3) has been prepared. From this /pseudosymmetrical: (see text) intermediate the two enantiomeric bromo derivatives 8 (R) and 20 (S) have been synthesized (cf. scheme 4) by altering the sequence of the reactions (cf. scheme 3). A Grignard reaction starting from the two bromo compounds 8 and 20 and from cyclododecanone 1 produced after hydrogenolysis the two enantiomeric dialcohols 9 and 21 (1 + 8 → 9, 1 + 20 → 21, cf. scheme 5). The subsequent transformations led to the two enantiomeric olefin derivatives 12 and 24. Oxidation of 12 with peracid produced a mixture of the two epoxy-sulfones 13 and 14 (cf. scheme 6). The olefin-derivative 24 was oxidized to the corresponding mixture of 25 and 26. A one pot cyclofragmentation (cf. [4] and scheme 6) produced a mixture of (E)- and (Z)-3-methylcyclopentadec-4-en-1-one (13 + 14 → 15 + 16, 25 + 26 → 27 + 28). The final hydrogenation led to natural (R)- and unnatural (S-muscone (3-methylcyclopentadecanone). The achiral starting material has been transformed to the desired optically active target products without loss of material with undesired absolute configuration. The authors used the notion of chiral economic synthesis to characterize synthetic sequences with the above mentioned features.

Notizen: The structures of cyclic polyketones, their hydrates and reduction products were studied in different solvents by 13C-NMR. spectroscopy. In dimethylsulfoxide solution rhodizonic acid (1), croconic acid (2) and squaric acid (3) exhibit signal averaging. In anhydrous tetrahydrofuran 1 and 2 could be observed as non-dynamic species. The spontaneous reactions of dodecahydroxycyclohexane (5) and decahydroxycyclopentane (‘leuconic acid’) (6) and the sequence of formation of ring-contracted products were investigated. Key intermediates could be clearly identified which support the mechanism proposed earlier involving a benzylic acid type rearrangement followed by decarboxylation and subsequent redox reactions.

Notizen: In order to test the effects of the replacement of phenylalanine by carboranylalanine (Car) in biological ligand-acceptor interactions, Z · Ala-Ala-Car · OH (1) and Ac · Car · OEt (2) were synthesized and their reactions with chymotrypsin studied. The two compounds proved to be good inhibitors with K(i) values of 3 · 10-4M (1) and 8.6 · 104M (2); the K(i) of Z · Ala-Ala-Phe · OH (1a) is 1 · 10-3M. The inhibition constants were determined by a new photolytic technique, inhibition of photoaffinity labelling by Z · Ala-Ala-Phe(pN3) · OH. Ac · Car · OEt is not hydrolysed by chymotrypsin. The findings indicate that the carboranyl group can interact with the ‘phenyl recognition site’ of the enzyme to produce the binding that is characteristic of aromatic amino acid residues. However, some kind of distortion in the region of the ‘mechanistic site’ must be postulated in order to account for the failure of hydrolysis. Some possible effects of the replacement of aromatic amino acids by Car in peptide hormones on hormone-receptor interactions are discussed.

Notizen: 1,3-Cyclobutanedione derivatives from keteneThe dimerisation of ketene leads mainly to the methylidene-β-lactone ‘Diketene’ 2c. It is shown, that also a small amount of the symmetrical dimer, 1,3-cyclobutadione 1c is produced, which under the reaction conditions is acetylated to 3-acetoxycyclo-butenone (5).

Notizen: Synthese von 4-(4′-Methyl-2′-oxo-cyclohex-3′-en-1′-yl)-pentanal und dessen Umwandlung in Spiro[4.5]decan- und 1,6,7,7a-Tetrahydro-2H-inden-DerivateEs wird die Synthese von 4-(4′-Methyl-2′-oxo-cyclohex-3′-en-1′-yl)-pentanal als ein (1:1)-Gemisch von zwei Diastereoisomeren 10A und 10B auf folgendem Weg beschrieben: Die Umsetzung des Grignard-Reagens von 1,1-Äthylendioxy-3-brom-propan (2) mit 2-Methoxy-4-methyl-acetophenon (1) ergab 1,1-Äthylendioxy-4-hydroxy-4-(2′-methoxy-4′-methyl-phenyl)-pentan (3), welches sich mit methanolischer Salzsäure in 2-Methoxy-5-(2′-methoxy-4′-methyl-phenyl)-5-methyl-tetrahydrofuran (7A,B) umwandeln liess. Durch Birch-Reduktion von 7A,B wurde 4-(2′-Methoxy-4′-methyl-cyclohexa-1′,4′-dien-1′-yl)-pentan-1-ol (8), und danach durch milde Hydrolyse 4-(4′-Methyl-2′-oxo-cyclohex-3′-en-1′-yl)-pentan-1-ol (9A,B)2 erhalten. Oxydation von 9A,B lieferte schliesslich den erwähnten Keto-aldehyd 10A,B. Einige Produkte von Nebenreaktionen, nämlich 4, 5, 11, 12 und 13A,B, sind auch beschrieben.Der Keto-aldehyd 10A,B liess sich in ein Gemisch, bestehend aus drei Diastereo-isomeren A, B und C von 1-Hydroxy-4,8-dimethyl-spiro[4.5] dec-7-en-6-on (15) und aus zwei Diastereoisomeren A und B von 1,5-Dimethyl-1,6,7,7a-tetrahydro-2H-inden-3-carbaldehyd (14), umwandeln. Für diese aldolartigen Cyclisierungen wurden vier verschiedene Methoden verwendet: (a) Stehenlassen in Tetrachlorkohlenstoff-lösung, (b) Behandlung mit etwas Trifluoressigsäure in Chloroformlösung, (c) und (d) Schütteln einer Ätherlösung mit wässeriger Salzsäure oder Natronlauge. Oxydation von 15A und 15C lieferte eines der Diasteroisomeren von 4,8-Dimethyl-spiro[4.5]-dec-7-en-1,6-dion (16A), und Oxydation von 15B führte zum anderen (16B).

Notizen: Synthesis of fulvenes via 1-chloroaklyl-acetatesThe synthesis of fulvenes (5) via l-chloroalkyl acetates (3) is extended to 6-alkyl-fulvenes with branched side-chains, to 6-phenylfulvene (5f) and 6-(2-furyl)fulvene (5g), as well as to 6-vinylfulvenes (5h and 5i) containing chlorine and acetoxy-substituents in ω-position. The reaction is carried out at low temperature under water-free conditions. The purification of the reaction products is simple. - An improved procedure for the preparation of pure fulvene (5a, R=R′=H) is reported.

Notizen: Activated quinones: substitution reactions by methoxy-carbonyl-1,4-benzoquinone of azulenes, benzofuran and indoles; regiospecific syntheses of polymethoxy-fluorenones; a new synthesis of the 2,6-dihydro-naphtho[1,2,3-cd]indol-6-one system.We present new electrophilic substitution reactions of azulenes and 5-membered heterocyclics by methoxy-carbonyl-1,4-benzoquinone. Hydroquinones 3a and 5 are prepared from azulene, and 3b from guaiazulene (see Scheme 1). Benzofuran undergoes α- and β-substitution (hydroquinones 9 10) (see Scheme 2). Only β-substitution is observed with indole (hydroquinone 20) (see Scheme 4). After methylation, saponification and intramolecular acylation of the substituted indoles 22c, 22d, derivatives of 2,6-dihydro-naphtho[1,2,3-cd]indol-6-one have been obtained. Spectral data prove the presence of the methylidenequinone tautomer. By protonation or alkylation at the carbonyl group of 23, the violet, highly delocalized 16π-electron systems 25 are generated. Analogously, polymethoxy-fluorenones have been prepared from methoxylated diphenylquinones 15 (see Scheme 3). They also are transformed by protonation and alkylation to the highly coloured and delocalized 12 π-electron systems 18. By contrast, anthracene is not substituted by methoxycarbonyl-1,4-benzoquinone, but undergoes cycloaddition to the triptycene derivative 1 (see Scheme 1). A summary is presented of previously described reactions of activated quinones.

Notizen: An ab initio study of α-seleno carbanions show that they are subject to appreciable polarization and stereoelectronic effects. Like in α-thia carbanions, the equatorial e forms are more stable than the axial a forms, one of the stabilizing contributions being the conformation dependent (C-lone pair, σ* Se—Z) interaction. The carbanion stabilizing effect of the α-Se atom is about 3 kcal/mol larger than that of the sulfur analog. As in the case of the sulfur no specific effect of the d orbitals is found.

Notizen: The radical anions of 6a-thiathiophthenes ([1,2]dithiolo[1,5-b] [1,2]dithioles), I(R), convert into those of 4H-thiapyran-4-thiones, III(R), via cis-trans isomerization. The reaction is slowed down when the size of the substituent R in the 2,5-positions of 6a-thiathiophthene increases, and it is prevented by the introduction of a 3,4-polymethylene bridge. The primary and the secondary radical anions, I(R)\documentclass{article}\pagestyle{empty}\begin{document}$ ^{\ominus \atop \dot{}} $\end{document} and III(R)\documentclass{article}\pagestyle{empty}\begin{document}$ ^{\ominus \atop \dot{}} $\end{document}, respectively, exhibit very similar hyperfine splitting patterns. E.g., in the case of the unsubstituted 6a-thiathiophthene, I(H), and 4H-thiapyran-4-thione, III(H), the proton coupling constants are aH2,5=6.72 and aH3,4=1.73 Gauss for I(H)\documentclass{article}\pagestyle{empty}\begin{document}$ ^{\ominus \atop \dot{}} $\end{document}, and aH2,6=6.35 and aH3,5=2.07 Gauss for III(H)\documentclass{article}\pagestyle{empty}\begin{document}$ ^{\ominus \atop \dot{}} $\end{document}. In contrast to I(H)\documentclass{article}\pagestyle{empty}\begin{document}$ ^{\ominus \atop \dot{}} $\end{document}, cis-trans isomerization could not thus far be proved to occur with its 1,6-dioxa-analogue, IV(H)\documentclass{article}\pagestyle{empty}\begin{document}$ ^{\ominus \atop \dot{}} $\end{document}, since no ESR. spectrum of the radical anion of 4H-pyran-4-thione, V(H), was detected upon reduction of IV(H).

Notizen: Leaf-gland Pigments: Coleon L, a New Diosphenolic Compound from Coleus somaliensis, S. MOORE; Revision of the Structures of Coleon H, I, I′ and KFrom leaf-glands of C. somaliensis a new, highly oxidized diosphenolic hydroquinone belonging to the abietane series was isolated in minute quantities. The new compound, coleon L (4c; C24H30O10), is very labile and transformed into its tautomer coleon K (5d) on standing in solution. 1H-NMR. spectra of coleon L showed clearly that the points of attachment of the two acetoxy groups are at C(3) and C(16) contrary to the positions expected from our previously published structure 3 for coleon K. Application of a recently elaborated conversion of trans-A/B-6,7-diketones of type 5 into the cis-isomers 6 allowed to assign unambiguously the β-configuration to the hydroxyl group at C(3) using pyridin induced solvent shifts. This confirmed structure 4c and 5d for coleon L and K, respectively. Based on similar reasons, the configuration at C(3) of coleon H, I and I′ had to be revised, the structures of these coleons being 4b, 5b and 5c, respectively.

Notizen: The ESR. spectrum of the relatively unstable radical anion of diphenylcyclo-propenone (II) has been observed upon electrolytic reduction of II in N,N-di-methylformamide and 1,2-dimethoxyethane. Simple MO models account well for the π-spin distribution and for the restricted rotation of the phenyl substituents in II\documentclass{article}\pagestyle{empty}\begin{document}$ ^{\ominus \atop \dot{}} $\end{document}. A rather facile loss of a CO molecule by II\documentclass{article}\pagestyle{empty}\begin{document}$ ^{\ominus \atop \dot{}} $\end{document} results in formation of the radical anion of tolane (diphenylacetylene; III). No ESR. spectra could be obtained for the radical anions of dialkylcyclopropenones which are even shorter-lived than II\documentclass{article}\pagestyle{empty}\begin{document}$ ^{\ominus \atop \dot{}} $\end{document}, although decay by decarbonylation seems to be less favoured with them than with II\documentclass{article}\pagestyle{empty}\begin{document}$ ^{\ominus \atop \dot{}} $\end{document}. In presence of air, electrolytic reduction of either II or its dimethyl and di-t-butyl analogues yields the correspondingly disubstituted semidione anions.

Notizen: Reactions with derivatives of γ-chloroacetoacetic acidEthyl γ-chloroacetoacetate reacts with ammonia to give ethyl β-amino-γ-chloro-crotonate; with aniline, however, β-anilino-crotonic acid γ-lactone is formed. The reaction of ethyl α-cyano-γ-chloro-acetoacetate with arylamines yields 1-aryl-2-amino-3-ethoxycarbonyl-pyrrolin-4-ones.

Notizen: The Structure of Cyclosporin CThe structure of cyclosporin C (2), a minor antifungal metabolite from Trichoderma polysporum (Link ex Pers.) RIFAI has been elucidated. Hydrolytic cleavage and spectroscopic evidence show that cyclosporin C is a neutral oligopeptide of 11 amino acids linked together in a 33-membered ring. Cyclosporin C (2) differs from the main metabolite cyclosporin A (1) [2] [4] only by containing L-threonine in the place of L-α-aminobutyric acid as has been shown by the conversion of 2 into 1. 13C-NMR. spectra and study of molecular models suggest that cyclosporin C (2) has the same molecular conformation as 1, which is best described as a twisted β-pleated sheet held together in a conformationally stable form by intramolecular hydrogen bonding.

Notizen: Incorporation experiments with (3H and 14C) doubly labelled farnesols into cantharidinAfter injection of 11′, 12-[3H]-7-[14C]-farnesol or 11′, 12-[3H]-5,6-[14C]-farnesol, the 3H-label is located specifically in the C(9)-methyl-group of cantharidin, whereas the 14C-labelling pattern follows an incorporation via acetic acid (Scheme 4). C-Atoms 5, 6 and 7 from the middle part of the farnesol molecule are utilized for cantharidin biosynthesis to an extent that is about 2.1-11% of the incorporation rate of the methyl groups C(11′) and C(12), depending on the position of the 14C-label in farnesol. These results confirm our earlier hypothesis [1] that the C10-molecule cantharidin is biosynthesized from the C15-precursor farnesol which is cleaved between C(1)-C(2), C(4)-C(5), and C(7)-C(8). The synthesis of 7-[14C]-farnesol and of 5,6-[14C]-farnesol is described.

Notizen: Synthesis and NMR. Spectra of Novel Lanthanide-Cobalt Sandwich CompoundsThe reaction of [(C5H5)Co{P(O)(OR)2}2{P(OH)(OR)2}] (3, R = CH3, C2H5) with lanthanide(III) compounds yields the cationic trinuclear complexes [{(C5H5)Co[P(O)(OR)2]3}2Ln]⊕X⊖ (2, R = CH3, C2H5; Ln = La, Eu, Pr; X = BF4, BPh4). According to thermogravimetric and NMR. studies these compounds do not contain additional coordinated water molecules. It is therefore supposed that the central lanthanide ion has a regular sixfold coordination of phosphoryl ligands. The 31P- and 1H-NMR. spectra of 2 (R = CH3; Ln = La, Eu, Pr) and 3 are discussed. It can be shown that the Fermi contact shift as well as the coordination shift make significant contributions to the observed lanthanide induced shift of the cyclopentadienyl signal.The dominating influence of the Fermi contact interaction on the 31P chemical shift is in accord with theoretical considerations and comparable experimental values. The temperature dependence of the proton chemical shifts of 2 (R = CH3; Ln = Eu) is also discussed.

Notizen: Stereoselectivity and Reactivity in the 1,3-Dipolar Cycloaddition of Chiral N-(Alkoxyalkyl)nitronesThe stereoselectivity in the reaction of hydroxy-oxime 1 with acetaldehyde and methyl methacrylate yielding the diastereomeric isoxazolidine-ribosides 9-12 was determined to be 93%. The predominant adducts 9 and 10 were cleaved to the diastereomeric isoxazolidines 19 and 20, respectively, which upon oxidation gave the same optically active 2-isoxazoline 21, thus demonstrating the participation in the cycloaddition of both (E/Z)-isomeric nitrones 13 and 14. Based upon comparison of the optical rotations, the isoxazolidines 7, 8, 19 and 20 and the 2-isoxazolines 21 and 22 possess the same chirality, found to be R by correlating 7 with (+)-(S)-citramalic acid. - Since the hydroxy-oximes 1 and 36 showed the same stereo-selectivity in the reaction with formaldehyde and methyl methacrylate, the trityl group of 1 does not influence the stereoselectivity in the cycloaddition. The hydroxyoxime 38 led in the same type of reaction to the isoxazolidines 7, 8, 19 and 20 possessing (S)-chirality, the stereoselectivity (79-95%) being similar to the one observed with 1 (67-95%). The explanation of this stereoselectivity is based upon a stereoelectronic effect in the transition state of the cycloadditions (kinetic anomeric effect). As predicted, the N-(alkoxyalkyl)nitrones showed enhanced reactivity in the cycloaddition with unactivated olefins (leading to 47, 48, 50 and 51). The importance of exo vs. endo approach of the dipolarophile was evidenced by reacting 1 with formaldehyde and methyl acrylate giving predominantly 57 with (5S)-configuration. - Use of the hydroxy-oxime 65 allows synthesis of optically active isoxazolidines with regeneration of the starting hydroxy-oxime.