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Notes: 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.

Notes: 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).

Notes: 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).

Notes: 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).

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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).

Notes: 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.

Notes: 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).

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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).

Notes: 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).

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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).

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: The Constitution of LoroglossineLoroglossine, a characteristic constituent of orchids, is shown to be bis[4-(β-D-glucopyranosyloxy)-benzyl]-(2R, 3S)-2-isobutyl-tartrate (1). Base catalysed hydrolysis and esterification with diazomethane gave 1 mol-equiv. of dimethyl (+)-2-isobutyl-erythro-tartrate ((+)-3) and 2 mol-equiv. of a glucoside which after acetylation formed 4 identical with a synthetic sample. The structure of (+)-3 follows from the synthesis of (±)-3 by osmium tetroxide oxidation of isobutyl-maleic acid anhydride and subsequent esterification. The absolute configuration of (+)-3 was based on Horeau experiments and NMR. data of the diastereomeric mixture of its esters 15 and 16 and pure 15 with (S)-(+)- and (R)-(-)-α-phenyl-butyric acid, respectively.

Notes: Heterocyclic dienamines III. A re-examination of the reaction of Fischer's base on tetracyanoethyleneDepending on the order of addition, Fischer's base 5 (1,3,3-trimethyl-2-methylidene-indoline) reacts 1:1 with tetracyanoethylene to give either the tricyanovinylation product 6 or the spiro compound 7. A skeletal rearrangement of a zwitterionic intermediate can explain the formation of the spiro compound. The latter undergoes a thermal isomerization yielding by ring expansion the tetrahydroquinoléine 8. On reaction with LiAlH4 or CH3ONa 7 and 8 lead both to triazatetracycles. All structures are assigned on the basis of spectral data.

Notes: 2-Aza-7-oxa-twistanes (or 2-oxa-7-aza-twistanes, respectively)Die nicht mit den IUPAC-Regeln übereinstimmende Numerierung (b): 2-Aza-7-oxa-twistane, Substituent an C(10) (vgl. Korrekte Nomenklatur (a): 2-Oxa-7-aza-twistane, Substituent an C(5)), wurde zwecks besserer Übersicht und Vergleichsmöglichkeit mit anderen 2,7-Dihetero-twistanen und -isotwistanen, Für eine umfassende Übersicht vgl. [2], speziell auch mit den korrekt numerierten C(10)-substituierten 2-Aza-7-oxa-isotwistanen c deshalb gewählt, weil dadurch in diesen beiden Verbindungstypen b und c, welche chemisch ineinander überführbar sind (vgl. vorliegende Arbeit), sich entsprechende Atome gleich numeriert werden Können. Dadurch erhält je das den Substituenten tragende C-Atom die Nummer 10 und je das zwischen C(10) und N(2) liegende Brückenkopfatom die Nummer 1. Beim Twistan d wurde die Doppelbindung entsprechend ihrer Herkunft aus einem C(10)-substituierten Twistan b als in Stellung 9 bezeichnet. Vollständigkeitshalber sind die der korrekten Nomenklatur (vgl. a) entsprechenden Namen der Verbindungen 10-13 und 22, 23 und 25 nachfolgend aufgeführt; 10: 5N (7)-Brom-2-oxa-7-aza-twistan; 11: N(7)-Methyl-5N (7)-2-oxa-7-aza-twistan; 12: 2-Oxa-7-aza-twist-4-en; 13: N(7)-Methyl-2-oxa-7-aza-twist-4-en; 22: N(7)-Methyl-5O (2)-acetoxy-2-oxa-7-aza-twistan; 23: N(7)-Methyl-2-oxa-7-aza-twistan-5O (2)-ol; 25: N(7)-Methyl-2-oxa-7-aza-twistan. and 2-aza-7-oxa-isotwistanes

Notes: Of the isoelectronic 6-electron systems 1a, 1b, 1c (Table 1) the deprotonated amides 2 might be useful derivatives for amine acidification (eq. (1)) if the carbonyl group is sterically protected as shown in 3. The tetrasubstituted succinimides 4, 5, 7, 8 and 9 (diacylamines) undergo the reactions (b), (c) and (d) of Scheme 1 with various bases. Besides deprotonation, the ‘self addition’ to give dimers 4b, 5b, 8b and 9b is the most prominent transformation (Table 2). Only in 9 is the steric hindrance to carbonyl addition large enough to get the lithiomethyl-succinimides 9c in 80% yield (sec.BuLi/THF/HMPT/-100°) as evidenced by derivatization with alkyl halides, aldehyde, ketones, methyl benzoate, and chloro trimethylsilane (→9d - 9j, Table 3). The possible structures and bonding descriptions for 9c which ‘decomposes’ above -40° are discussed; the acidity of the precursor 9 is shown by equilibration studies to be comparable with that of diphenylmethane.

Notes: The electrochemical reduction of the cyclohex-2-enones 1a-1e (mercury cathode, CH3CN, Bu4NBF4) was studied by means of cyclic voltammetry, d.c. polarography, coulometry and chemical product analysis. Compounds 1a-1c give a mixture of the hydrodimers 4 and 5 via formation of the radical anion 2 by an irreversible one electron transfer, followed by protonation and dimerization of the allylic radical 3. The 6-halocyclohex-2-enones 1d and 1e exhibit two distinct reduction waves. The first corresponds to an irreversible two electron transfer with formation of the halide anion and the enolate anion 6 which gives 1b by protonation. The second wave corresponds to a quasi-reversible one electron transfer to 6 to afford the radical dianion 7 (Scheme 2).

Notes: On the Base-Catalysed H/D-Exchange of the Acetylenic Hydrogen Atom in Aromatic Alkynyl CompoundsH/D-exchange rates for a number of compounds of the general type 1 (X = p-CH3O, m-CH3O, p-CF3, m-CF3, p-CH3, p-Cl, H; Z — O, NH, CH2) were determined in N-methyl-pyrrolidine (NMP)/D2O mixtures at 25° (see Table 1).It is shown that the log k values of the H/D-exchange correlate nicely (r = 0.995) with the chemical shift of the acetylenic proton in 1. Thus, the H/D-exchange rate is given by log k (min-1) = 2.91 · δ (ppm) - 7.79 for the NMP/D2O mixture at 25°.

Notes: CNDO/2, MINDO/3 and ab initio molecular orbital calculations are used in a study of conformational isomerism, protonation site and mechanism of protonation of the title compounds.

Notes: Verbenone 1 or 2 is converted in three steps to ipsdienol 9 or 10 respectively. The diastereoisomeric 2(10)-pinen-4-ols 6 and 7 (or 5 and 8), wich have identical chirality at the carbon atoms bearing OH groups, afford ipsdienol 10 (or 9 respectively) with the same optical purity as the starting material.

Notes: 15N-Chemical shifts of 32 enamines, 11 enaminoketones and 28 closely related amines have been determined with the isotope in natural abundance. In order to eliminate substituent effects, differential chemical shifts Δδ(N) are defined as δN(amine)-δN(enamine). This parameter is shown to correlate well with the free enthalpy of activation ΔG# for restricted rotation about the N—C(α) bond in enamines with extended conjugation. Δδ(N) values of substituted anilinostyrenes correlate also with 13C-chemical shifts of the β-carbon in the enamine system and with Hammett σ-constants of the aniline substituents. The experimental results suggest that differential 15N shifts are a useful probe to study n, π-interaction in enamines.

Notes: New β-lactam antibiotics. Functionalisation of 3-hydroxy-3-cephem-4-carboxylic esters through the Wittig reactionThe 3-hydroxy-ceph-3-em-esters 1a, b reacted smoothly with stabilized phosphor-ylids to give a series of derivatives which were converted into the microbiologically active acids 14a, c, 15c and 20 by known procedures. The synthesis of the amides 23, 24, 26 and of the ester 28 from the 3-carboxymethyl-derivative 19 is also reported.

Notes: A new metabolite, verrucarin K (C27H34O8) has been isolated from a strain of Myrothecium verrucaria (ALBERTINI et SCHWEINITZ) DITMAR ex FRIES. On the basis of spectral and chemical evidence structure 1 was assigned to the new compound. Base-catalysed hydrolysis yielded verrucarinolactone (5), E,Z-muconic acid (6) and trichotheca-9, 12-diene-4,15-diol (3). The implications of 1 in the trichothecane biosynthesis are discussed.

Notes: Synthese und Umlagerung von 7-Halo-bicyclo[3.2.0]hept-2-en-6-olenDie Reaktion von verschiedenen 7-halogen-substituierten Bicyclo[3.2.0]hept-2-en-6-onen mit komplexen Metallhydriden oder mit Methylmagnesiumiodid zu den entsprechenden 7-Halo-bicyclo[3.2.0]hept-2-en-6-olen verläuft unter Angriff des Nucleophils trans zum Halogen, um dem vicinalen Kohlenstoff-Halogen-Dipol auszuweichen. In Gegenwart von starken Basen unterliegen die Halohydrine einer Umlagerung, die je nach der durch die intramolekularen Wechselwirkungen bedingten Konformation, entweder unter Hydridverschiebung zu Bicyclo[3.2.0]hept-2-en-6-onen oder, unter Ringverengung, zu Bicyclo[3.1.0]hex-2-en-6-carbaldehyden führt.

Notes: The title compound 2 was synthesized from the intermediates 3 and 4. It is identical with the rearrangement product of 1 and glyoxal, of which the X-ray structure analysis is described.

Notes: The tricyclic alcohols 3-7, derived from the corresponding ketones 1 and 2 (Scheme 1), by action of acids underwent dehydration with skeletal rearrangements. Dehydration of 3 and 4 with POCl3/pyridine (procedure A) afforded the polycyclic hydrocarbons 9, 10, and 12, 13, respectively. With TsOH (procedure B), on the other hand, 3 and 4 gave homo-triquinacenes 10 and 14 respectively, as well as the polycyclic ethers 11 and 15 (Scheme 2). Hydrocarbon 9 (or 12) was converted into 10 FSO3H to the tertiary alcohol 16 (Scheme 4). Plausible mechanisms for these transformations are summarized in Scheme 8. Dehydration of the secondary alcohols 5 and 7 was effected by procedure A. While treatment of alcohol 5 with POCl3/pyridine yielded two isomeric hydrocarbons 17 and 18, similar dehydration of its epimeric alcohol 7 afforded hydrocarbon 21 as the sole product. The tertiary alcohol 6 was dehydrated by both procedures to yield two isomeric hydrocarbons 19 and 20 (Scheme 5). Hydrocarbon 20 was converted into 19 by procedure B (mechanisms, Scheme 10). Reaction of ketone 2 with CF3COOH gave the addition product 22 converted into vinylsulfonyl fluorides 24 and 25 by treatment with FSO3H (Scheme 6). Homo-triquinacenes 10 and 14 reacted smoothly with 4-phenyl-1,2,4-triazoline-3,5-dione to give the ‘ene’-reaction products 26 and 27, respectively.

Notes: New Cyclopeptides from Trichoderma polysporum (LINK EX PERS.) RIFAI: Cyclosporins B, D and ECyclosporins represent a new group of biologically active metabolites produced by Trichoderma polysporum (LINK EX PERS.) RIFAI and other fungi imperfecti. The structures of the main components, cyclosporins A (1) and C(3) have been determined as neutral cyclic oligopeptides composed of 11 amino acids, among them a new C9-amino acid [2-4]. In addition, three minor metabolites, cyclosporins B, D and E, have now been isolated and characterized. Chemical investigation, spectroscopic evidence and X-ray analysis led to the structural formulae of cyclosporins B (2) and D (4). Both compounds have the same sequence of amino acids as cyclosporin A (1), with the exception of L-α-aminobutyric acid, replaced in cyclosporin B (2) by L-alanine and in cyclosporin D (4) by L-valine, respectively. Cyclosporins undergo a characteristic intramolecular N,O-acyl migration to furnish the corresponding basic isocompounds. The antifungal activities of cyclosporins are reported.

Notes: New 18-Substituted Steroids. I. 18-MethylideneprogesteroneThree independent syntheses of 18-methylideneprogesterone, the first representative of a new group of biologically highly active steroidal compounds, are described. In the first approach 3-acetoxy-20-oxo-5-pregnen-18-carbonitril (2) is transformed into the final product by a reaction sequence involving the Cope degradation of the N-oxide 6 of the corresponding tertiary aminomethyl derivative. The Wittig reaction 3,3,20,20-Bis(äthylendioxy)-5-pregnen-18-al (11) represents the crucial step in the second synthesis. In the last procedure the 18-methylidene-20-oxo grouping is generated by fragmentation of an 18,21-bridged 1,3-diol system (19). The two former methods are very versatile and generally applicable for the synthesis of other analogues.

Notes: Synthesis, crystal structure and thermal dehydration of CsMnF4 · 2H2OThe preparation of a new fluoromanganate (III)-complex CsMnF4 · 2H2O is reported. It crystallizes in the monoclinic space group C2 with a = 11.891(2) Å, b = 6.589(1) Å, c = 10.558(1) Å, β = 131.46(1)° and Z = 4. The crystal structure has been solved from diffractometer data by heavy-atom methods and refined to a conventional R-value of 1.8% (including the contributions of three hydrogen atoms in measured and one in calculated positions). The structure is characterized by isolated, tetragonally distorted [MnF4(OH2)2]-octahedra with Mn-F-distances from 1.801(8) Å to 1.870(7) Å and Mn-O-distances of 2.146(6) Å and 2.268(6) Å. Cesium exhibits an irregular 10-coordination by 8 F-atoms and 2 O-atoms (mean values for the two independent cesium ions: Cs-F = 3.17 Å and 3.21 Å, Cs-O = 3.32 Å and 3.29 Å). The [MnF4(OH2)2]-octahedra are connected to six neighbouring octahedra by hydrogen bonding.The dehydration of the complex has been studied by thermoanalytical methods and power x-ray-diffractometry. The unit cell of the dehydrated compound, CsMnF4, is tetragonal with a = 7.936(1) Å and c = 6.341(1) Å. A close relationship to the structure of CsFeF4, which is a superstructure variant of the T1A1F4-type[6], is indicated by the similarity of the corresponding unit cells and preliminary structure factor calculations. A proposition for the crystal structure of CsMnF4 is developed on the basis of (2 + 2 + 2)-orthorhombic distorted MnF6-octahedra.

Notes: Reactions of oxygenated cobalt(II) complexes. IX. Oxidative properties of tetrakis(ethylenediamine)-μ-peroxo-μ-hydroxo-dicobalt(III)VIII s. [1].[(en)2Co(O2, OH)Co(en)2]3+ (a) reacts with I- in acidic aqueous solution according to: CoIII(O2, OH)CoIII + 21- + 5H+ ⇀ 2CoIII + 3H2O + I2. Using I- in excess first order rate constants are obtained which, to a first approximation, are independent of [I-]. Comparison with kinetic data of deoxygenation of [(en)2Co(O2, OH)Co(en)2]3+ under analogous conditions suggests that both reactions have the same rate determining step. The singly bridged species [(en)2(H2O)CoO2Co(H2O) (en)2]4+ is shown to be the reactive intermediate in the iodide oxidation (Schema 2).

Notes: Addition of nitrogen trioxide to indene and alkylindenesN2O3 adds to indene and homologous yelding pseudonitrosites which are converted to aminoindanes. Treatment of the pseudonitrosites with alcoholic potassium hydroxide gives the correspondent nitroindenes.

Notes: Crossed conjugated Cyanines and Merocyanines, obtained from Salts of 1-substituted 2,3-Dimethyl-quinoxalines. (A second type of vinylogous Indigo-imides.) Preliminary Communication.On dissolving quaternary salts of 2,3-dimethylquinoxaline in dimethylformamide or dimethylsulfoxide, a spontaneous reaction takes place: the title compounds are isolated from the reaction mixtures; they are easily oxidized, e.g. by MnO2. Mechanistic aspects are discussed.

Notes: Total Synthesis of (+)-D-Homoestrone 3-methyl etherA novel total synthesis of (+)-D-homoestrone 3-methyl ether (21) is described starting from (S)-8a-methyl-3,4,8,8a-tetrahydro-2H, 7H-naphthalene-1,6-dione (1) as a chiral synthon for the rings C and D. The key step involves alkylation of the derived 3 with m-methoxyphenacyl bromide (4) as an AB-building block to give the dioxo-secosteroid 5. Hydrogenation of 5 affords the trans-decalone 11. As by-products the epimeric cis-decalones 12 and 13 were characterized. Cyclization of 11 leads under kinetic control predominantly to the Δ9(11)-tetraene 14. Catalytic hydrogenation of 14 and subsequent modification in ring D give the title compound 21. It was found that 14 and also the derived Δ8-isomer 15a add hydrogen from the α-face of the molecule to an extent of about 80%. The 8α-D-homoestrone derivatives 20a and 23 as well as the 9β-isomers 19a and 22 were characterized.

Notes: The higher homologues of n-alkanes H(CH2)NH with N 〉 ∽ 13 yield photoelectron spectra in which the C2s-bands merge to form a double humped, unresolved C2s-band system in the interval of I=15 to 25 eV [1]. It is shown that with the help of an equivalent bond orbital model one can derive a closed formula, which gives the individual C2s-band positions Ijm=-εj in function of N and j with sufficient accuracy, assuming the validity of Koopmans' approximation. The calculated Ijm values (j=1 to N) folded with an appropriate shape function for the individual C2s-bands reproduce the observed Franck-Condon envelope of the C2s-band system within narrow limits of error. However, a comparison of the observed total width of the C2s-band system with the computed one, indicate that for large n-alkanes (N≥ ∽ 13), the simplification which consists of taking into account only the interaction matrix elements between vicinal bond orbitals [2], is no longer a satisfactory one.

Notes: The crystal structure of 6-methyl-7,8-dihydropterine-monohydrochloride-monohydrateThe crystal structure of the title compound has been determined by X-ray analysis (direct methods) and refined with 990 structure amplitudes to R = 0.025. The crystal system is triclinic, space group P1, with unit cell dimensions a = 5.859, b = 7.686, c = 12.107, α = 71.84, β = 76.35, γ = 85.80. The molecule is protonated at the N(5)-position and is planar. The atoms H(19) and H(20) are with 0.818 Å above respectively with -0.705 Å under the plane.

Notes: Membrane Selectivity and Syntheses of Ionophores for Li+. Stability Constants in EthanolElectrically neutral, lipophilic complexing agents were prepared which induce Li+ selectivity in solvent polymeric membranes. Stability constants for group IA and IIA cations of one such ligand in ethanol have been determined. The selectivity behaviour of this ligand in membranes as well as in extraction systems is studied and discussed in terms of model considerations.

Notes: Preparation of heterocyclic substituted stilbenyl derivatives of 2H-1,2,3-triazoleSchiff's bases derived from 2- and 4-(p-formylphenyl)-2H-1,2,3-triazoles and o- or p-chloroaniline are reacted with various p-tolyl substitued aromatic heterocycles in the presence of dimethylformamide and potassium hydroxide or potassium t-butoxide to yield the corresponding heterocyclic substituted stilbenes (“Anilsynthesis”). In order to avoid opening of the 2H-1,2,3-triazole ring, the reaction is carried out without external heating. In many cases an improvement in yield is obtained by irradiation with UV. light at the beginning of the reaction.

Notes: Tetracarbonyliron Complexes of trans-Cycloalkenes and trans-CycloalkadienesRelatively stable olefin tetracarbonyliron complexes were obtained by reaction of Fe2(CO)9 with trans-cyclooctene (t-1), trans-cyclononene (t-2) and trans-cyclodecene (t-3) (Scheme 2) in pentane solution at room temperature. Furthermore, trans,cis-cycloocta-1,5- and -1,3-diene (t,c-7 and t,c-8) as well as trans,trans,cis-2,8,12-trans-bicyclo[8.4.0]tetradecatriene (t,t,c-9) gave stable complexes only with the trans-configurated double bond (Scheme 3).An olefin tetracarbonyliron complex was also obtained with bicyclo[4.3.1]deca-7,9-diene (10) which reacted only at the strained bridge-head double bond. The IR. spectra of the new complexes are in agreement with an equatorial position of the olefinic ligands in the trigonal bipyramide of the iron.

Notes: The 2-trimethylsilylethyl residue, a selectively cleavable carboxyl protecting groupIn a search for new carboxyl protecting groups suitable for use in peptide synthesis, 2-trimethylsilylethyl esters [-COOCH2CH2Si(CH3)3] of several N-protected amino acids have been prepared. These esters can be synthesized in good yields from Na-benzyloxycarbonyl-amino acids and 2-trimethylsilylethanol with dicyclohexylcarbodiimide in the presence of pyridine. They are stable under a wide variety of conditions used during coupling and work-up in peptide synthesis. For removal the 2-trimethylsilylethyl group is readily cleaved by fluoride ions, preverably using a quaternary ammonium fluoride in dimethylformamide. Some side reactions which occurred during the removal of the 2-trimethylsilylethyl group are discussed.Special attention has been paid to the question of racemization during the treatment with fluoride ions. No. evidence of racemization was found in any of the cases examined.

Notes: Charge Transfer Compounds of Metal Complexes. I. Bis(o-phenylenediamido)-Nickel Complexes as DonorsThe synthesis of monosubstituted bis(o-phenylenediamido)-nickel complexes NiL2=Ni(C6H3(NH)2R)2 where R = H, OCH3, Cl, sec-butyl, and of the disubstituted complex Ni(C6H2(NH)2 (CH3)2)2 is described. Substitution has a strong influence on the polarographically investigated reduction/oxidation behaviour of the complexes. Reaction of the nickel complexes with strong electron acceptors A (A = chloranil, tetracyanoethylene, 2,3-dichloro-5,6-dicyano-p-benzoquinone, 7,7,8,8-tetracyanoquinodimethane) yields solid compounds with a stoichiometric composition NiL2: A = 1:1. IR. And UV./VIS. Spectroscopic data indicate an ionic ground state of the solids. Electrical conductivities of solids are in the range 4,3·10-3 ω-1 cm-1 to 5·10-12 ω-1 cm-1 at 298 K with activation energies of 0.33 eV to 1.68 eV.In some cases solution equilibria in acetone or dichloromethane have also been investigated. The general scheme is: The tight ion pair NiL2+A- gives no ESR.-signal. Low temperatures or addition of R4NClO4 salts favour the formation of the ionic species.

Notes: The stereochemical structure of two reduction products of benzo[b]-5α-17β-hydroxy-androst-2-eno[2,3-e] [1,4]thiazine has been determined by 1H-NMR. Spectrometry using the INDOR technique.

Notes: Contribution to the asymmetric synthesis of bicyclic compounds catalysed by optically active amino acids. Synthesis of (S)-2-pyrrolidinepropionic acid and (R)-4-amino-5-phenylvaleric acidThe evaluation of literature data concerning the asymmetric cyclization of the prochiral monocyclic triketones 1 to the enediones 3 shows that catalysis with optically active α-amino acids of the (S)-series leads to an excess of products having the same absolute configuration as natural steroids at C (13), while those of the (R)-series favour the formation of the enantiomers (Scheme 1). With 1a as substrate an inverse asymmetric course was observed using the optically active β-amino acids 5, 8 and 10 as catalysts (Table 1). Furthermore, the synthesis of the optically active γ-amino acids 6 and 11 using the Arndt-Eistert process is described. The influence of these latter compounds on the asymmetric transformation of 1a into 3a has been investigated.

Notes: Identification of farnesol as an intermediate in the biosynthesis of cantharidin from mevalonolactoneSimultaneous injection of 2-[14C]-mevalonolactone (2-[14C]-1) and (E,E)-11′,12-[3H]-farnesol (11′,12-[3H]-2) into Lytta vesicatoria L. (Coleoptera, Meloidae) yields doubly labelled cantharidin (3). The remainder of the precursor farnesol, re-isolated from the insects after the incubation period, has incorporated 14C-radioactivity. The labelling pattern in this farnesol, as determined by two independent degradative reaction sequences, is in agreement with the isoprene rule. Since specific incorporation of farnesol (2) into cantharidin (3), and of mevalonolactone (1) into both, farnesol (2) and cantharidin (3) is observed, the sesquiterpene alcohol 2 acts as an intermediate in the biosynthesis of the C10-compound 3 (Scheme 1).

Notes: Singlet oxygen oxygenation of ambrein (1) and subsequent degradation of the primarily formed allyl hydroperoxides led to the naturally occurring ambergris odorants 2 to 5. The results allowed the postulate that 1O2 is an active reagent in the biodegradation of the tricyclic triterpene alcohol 1 in ambergris.

Notes: Compounds 2 to 7 were identified among the products obtained from ambrein (1) by potassium permanganate oxidation; (+)-dihydro-γ-ionone (3) was shown to have the S-configuration.

Notes: Carotenoids from Marine Sponges (Porifera): Isolation and Structure of the Seven Main Carotenoids from Agelas schmidtiiThe following carotenoids were identified in the marine sponge Agelas schmidtii: α-carotene ((6′R)-β, ε-carotene (1)), isorenieratene (ϕ,ϕ-carotene (2)), trikentriorhodin (3,8-dihydroxy-κ,χ-caroten-6-one (3)) and zeaxanthin ((3R, 3′R)-β, β-carotene-3, 3′-diol (4)). In addition, three previously unknown carotenoids called agelaxanthin A, B and C were isolated. Spectroscopical and chemical structure elucidation showed agelaxanthin A to be (3 R)-β, ϕ-caroten-3-ol (6) and agelaxanthin C to be a methoxy-19,3′,8′-trihydroxy-7,8-didehydro-β, κ-caroten-6′-one (7) with the methoxy group at C (2), C (3) or C (4). The limited data on age-laxanthin B were compatible with the structure of a 19-O-methyl derivative of agelaxanthin C.

Notes: Leaf-gland Pigments: Coleons U, V, W, 14-O-Formyl-coleon-V, and two Royleanones from Plectranthus myrianthus BRIQ.; cis- and trans-A/B-6,7-DioxoroyleanonesFrom leaf-glands of the South-African P. myrianthus (Labiatae) the following diterpenoids have been isolated and their structures established: coleon U, C20H26O5 (6, 11, 12, 14-tetrahydroxy-abieta-5, 8, 11, 13-tetraene-7-one, 2a); coleon V, C20H26O5 (11, 12, 14-trihydroxy-abieta-8, 11, 13-triene-6, 7-dione, 4a); coleon W, C22H28O8 (16(or 17)-acetoxy-6, 11, 12, 14, 17 (or 16)-pentahydroxy-abieta-5, 8, 11, 13-tetraene-7-one, 6); 14-O-formyl-coleon-V, C21H26O6 (14-formyloxy-11, 12-dihydroxy-abieta-8, 11, 13-triene-6, 7-dione, 4b); 7α-formyloxy-6β-hydroxyroyleanone, C21H28O6 (7α-formyloxy-6β, 12-dihydroxy-abieta-8, 12-diene-11, 14-dione, 1a); the already known 6β, 7α-dihydroxyroyleanone (1c) and a dimeric abietane derivative whose structure is not yet elucidated. This is the first record of a co-occurrence of coleons and royleanones in the same plant. In the course of chemical investigations of 4a and 4b the highly oxidized trans- and cis-A/B-6,7-dioxoroyleanones (5a and 5b) were obtained.

Notes: Basic Metals. II. Protonation and Alkylation Reactions of π-Cyclopentadienyl-metal-bis(tert.-phosphite) ComplexesFür «Basische Metalle. I» siehe [1].The complexes C5H5Co[P(OR)3]2 (R = CH3, C2H5) and C5H5Rh[P(OR)3]2 (R = CH3, C2H5, C6H5, C6H4-o-CH3) react with electrophilic agents E+, e.g. H+ and CH3+, to give [C5H5ME(P(OR)3)2]+. Salts of these cation have been isolated with BF4- and PF6- as the anions. The formation of compounds with direct M-H and M-CH3 bonds points to the pronounced Lewis-base properties of the metal atom in the starting complexes. The NMR. data of the cations [C5H5MH(P(OR)3)2]+ and [C5H5MCH3(P(OR)3)2]+ will be discussed.

Notes: The synthesis of phenathrenes substituted by nitrogen and oxygen atoms in position 9 and 10 by photolysis of 4,5-diphenyl-oxazol-2-ones (cf. Scheme 4) is described. Moreover an improved general procedure for the synthesis of benzoins in aprotic solvent (tetra-t-butylammonium cyanide in DMF/DMSO) is developed.

Notes: 1H-NMR.-spectra of a series of alloxazines and isoalloxazines and certain cationic derivatives were investigated (Tab. 2 and 5). Unequivocal assignment of all resonance signals was achieved in some compounds by selective deuteriation also by double resonance technique. The coupling constants were verified by computer simulation. Considerable enhancement of the signals due to H-C(9) and H-C(6) is found on decoupling of H3C-C(7), H3C-C(8) and H3C-N(10), resp. These results are compared with those obtained with FAD. The methyl resonance signal of the H3C-C(7) compounds give doublets due to coupling with H-C(6). The difference in chemical shifts observed upon successive formal introduction of methyl groups into the benzene nucleus of (iso)alloxazines indicates that the molecule becomes less planar thereby. The pyrimidine ring of (iso)alloxazines does not contribute to the ring current except by indirect effects via the carbonyl groups. The experimental data are compared with published MO calculations and discussed.

Notes: A series of isoalloxazine and alloxazine derivatives have been investigated by 13C-NMR. The synthesis of selectively 13C-enriched derivatives made it possible to assign unambiguously the signals due to the quaternary carbon atoms at position 4, 4a and 10a of the isoalloxazine ring system. The assignment of the other resonances was ensured by the use of selectively deuteriated and chemically modified compounds as well as by decoupling techniques. The assignments differ in part from those published by Breitmaier & Voelter [2] on FMN and FAD. The solvent dependence of the resonances has been studied in dioxan/water mixtures. The experimental data are compared with published MO calculations and discussed.

Notes: The Different Behaviour of Lysine Methyl Ester and its N,N′-Diacetyl Derivative under Electron ImpactThe base peak in the spectrum of lysine methyl ester is due to the fragment ion C5H10N (m/e 84), for which the cyclic structure g (Scheme 1) is deduced. During its formation from the [M-COOCH3]-ion an equilibration of both nitrogen atoms takes place (ion c, Scheme 1). The cyclic nature of ion m/e 84 is in agreement with the intensity of the corresponding ions in the spectra of homologues of lysine methyl ester (Fig. 1). Although in comparison with lysine methyl ester (1) N,N′-diacetyl-lysine methyl ester (7) shows the same general fragmentation pathway with formation of the ions [M-COOCH3] and [M-COOCH3-H2NCOCH3] (m/e 126), the exact fragmentation mechanism proves to the different. Two mechanisms are discussed for the formation of the ion m/e 126 from 7 (Schemes 2 and 3). The results are based on the spectra of labelled derivatives.

Notes: The pKa* values for nine acyclic, mono- and bicyclic α-, β- and γ-(trimethyl)ammonio acids, 1(α-γ), 2(α-γ) and 3(α-γ), respectively, have been measured in 50% aqueous ethanol. The comparison of these values with those for the nine homomorphous α-, β- and γ-acids, 4(α-γ), 5(α-γ) and 6(α-γ), respectively, permits an evaluation of the steric effect of the (trimethyl)ammonio groups which is super-imposed on their polar effect in the former acids. The pKa* values, corrected for the steric effect, correlate very well with the reciprocal distance between the positive nitrogen atom and the dissociable proton. This confirms our earlier conclusion that the strength of these acids is determined by the field effect of the (trimethyl)ammonio groups only, the inductive model failing to account for the results. The distinction between two different transmission mechanisms for the polar effect therefore becomes unnecessary, the inductive model appearing as an atomistic description of the field effect.

Notes: The configurations of a series of mono- and bis-Fe(CO)3 complexes of 12-oxa[4.4.3]-propella-2,4,7,9-tetraene (1) and of 11,13-dioxo-12-methyl-12-aza[4.4.3]propella-2,4,7,9-tetraene (7) as well as of a trienic aza-propellane complex have been studied in solution by 13C- and 1H-NMR. spectroscopy. Praseodymium-induced 13C-shifts of the metalcarbonyl carbon atoms and of the central carbon atom of the complexed diene systems are particularly sensitive and useful to prove exo- or endo-configuration of the tricarbonyliron ligand. In addition, H,H- and C,H-coupling constants of the complexes and parent compounds are reported and discussed.

Notes: Acetals of 1,2,3,4-tetraoxobutane: preparation and structure determination of rac- and meso-2,3,3,4,4,5-hexamethoxy-tetrahydrofuranOxidation of 3,4-dimethoxyfuran with 2 equiv. of bromine at -75° in the presence of triethylamine and methanol leads to a mixture of rac- and meso-2,3,3,4,4,5-hexamethoxy-tetrahydrofuran (cf. Scheme 1, 4 and 5). The structure of the crystalline rac-compound has been determined by X-ray analysis.

Notes: Synthesis and Transformations of Isoxazolidine-NucleosidesReaction of the oxime 12 with formaldehyde, acetaldehyde or acetone in the presence of methacrylic acid methylester leads in a highly stereoselective 1,3 dipolar cycloaddition of the corresponding nitrones to the protected isoxazolidine ribosides 13, 14, 20, 21 and 26 (Scheme 1 and 2).Using a new, mild procedure to effect detriylation, the cycloaddition products were transformed into the alcohols 16-19, 22-25 and 27.Cleavage of a mixture of the glycosides 16 and 17 yielded the N-unsubstituted isoxazolidine 29 in 65% optical purity while the cleavage of 27 gave optically pure 28.Alternatively, the isoxazolidine ribosides 13, 14, 16-18 and 26 were transformed via reductive cleavage of the isoxazolidine N-O bond and subsequent lactamization into the corresponding pyrrolidinone-ribosides 30, 33, 35, 42, 49 and 50, the ribitolyl pyrrolidinones 31, 34, 36-39 and 43-46 (see Scheme 4) and the ribitolyl isoxazolidine 47.

Notes: The crystal structure of 5-formyl-6,7-dimethyl-5,6,7,8-tetrahydropterineThe crystal structure of the title compound, a tetrahydropterine, has been determined by X-ray analysis (direct method) and refined with 1579 structure amplitudes to R = 0.054. The crystal system is triclinic, space group P1, with unit cell dimensions a = 7.171, b = 7.255, c = 12.369 Å, α = 100.64, β = 93.32, γ = 98.27°. The tetrahydropyrazine ring exists in a distinctly flattened conformation. The C(13)- and C(14)-CH3-groups possess a cis-configuration with axial position for C(13)-CH3 and equatorial for C(14)-CH3. The carbonyl-group of the N-formyl function has an (E)-configuration.

Notes: Nucleophilic Substitution Reactions of Hydroxysteroids using Triphenylphosphane/diethylazodicarboxylateNucleophilic substitution reactions by means of the title reagent on various more or less hindered steroid alcohols with suitable nucleophils in benzene is described. It was not possible to run this substitution process in the hitherto used solvent THF. Cholestan-3α-ol (1) was transformed to the 3β-substituted products 3β-benzoyloxy-cholestane (1a) and 3β-azido-cholestane (1b). Testosterone (2) affords with the corresponding nucleophils after short heating in benzene the inverted 17α-substituted products 3a, 3b and 3c. Analogously the 17α-azido-derivative 5a arises from 17β-hydroxy-androst-3-on (4). In the presence of a ketogroup in the substrate a competitive reaction can occur as it is shown in the case of cholestan-3-on (6): the products are the en-hydrazo-dicarboxylate-steroids 7a and 7b. The sterically very hindered 11α-position in 11α-hydroxy-4-pregnen-3,20-dion (8) can be transformed also to the 11β-azide 9a. The substitution of a 6β-hydroxy group in androstane-3β, 6β, 17β-triol-3,17-diacetate (10) to the 6α-azide 11a affords the elimination product 12 as main component. Trans-diaxial vicinal diols such as cholestane-2β,3α-diol (13) give a mixture of the α- and β-oxiranes 14a and 14b.

Notes: A gas chromatographic method of measuring the olive oil-gas partition coefficients is described. It is based on the relationship existing between the retention time of each substance and its solubility in olive oil used as a stationary liquid phase. The validity of this method has been tested by varying the length of the column, the percentage of liquid phase and the flow rate of the carrier gas. Using this technique, the partition coefficients of 24 hydrocarbons, 8 aliphatic, 6 aromatic and 10 chlorinated, have been determined (see Table 4).

Notes: The synthesis of mixed-ligand cobalt(III) complexes with (S)-aspartic-N-monoacetic acid ((S)-AMA) and different amino-acids Na[Co((S)-AMA)(AA)] (AA = gly, (R)- and (S)-ala, val, phe, ser and leu) leads to a mixture of cis-N- and trans-N-isomers. These isomers are formed stereospecifically. VIS., CD.- and NMR.-spectra are reported and a proposal is given for the absolute configuration of all the compounds isolated.

Notes: The cis-N/trans-N interconversion of the title compound containing glycine and (R)- or (S)-leucine has been studied by polarimetric and spectrophotometric techniques. Equilibrium constants were determined on the basis of kinetic and thermodynamic data. It is shown that the chirality of the bidentate amino-acid has a pronounced influence on the cis-trans equilibrium of these systems. Possible mechanisms of the interconversion reaction are discussed.

Notes: Steric effects on the dissociation constants of acyclic, mono- and bicyclic carboxylic acidsApparent pKa* values for the series of acyclic, mono- and bicyclic acids 1-14 have been measured in 50% (W/W) ethanol (see the Table). The dissociation constants of these acids decrease as the access of the solvent to the carboxylate group is hindered by the rest of the molecule. These results emphasize the importance of solvation in determining acid strength. New or improved syntheses of several of the acids investigated are reported.

Notes: Two acetylenic steroids, cholest-5-en-23-yn-3β-ol (5) and 26,27-dinorcholest-5-en-23-yn-3β-ol (3), and another unsaturated steroidalcohol, stigmasta-5,23-dien-3β-ol (7), were isolated from the sponge Calyx nicaaensis. The structures of these two acetylenic steroids were established by synthesis. Several attempts to synthesize the marine steroids alcohol calysterol (1), with a cyclopropene-containing side chain, starting from cholest-5-en-23-yn-3β-ol are also recorded. Addition of ethyl-diazo-acetate to the triple bond was performed, but the reduction to the methyl derivative yielded decomposition products.

Notes: 1H-NMR. behaviour of 1,3-diaryltriazenes in neutral and acidic solventsFormation and decomposition of 1,3-di-aryltriazenes can be studied by 1H-NMR. Triazenes decompose in acidic medium or by addition of isoamylnitrite: in the last case, the spectrum shows emission lines characteristic of the CINDP effect. At -80° the prototropic rate is slow enough to permit the observation of two aromatic systems.

Notes: Copper(0) does not catalyze the decomposition of dialkylcarbamoyl azides 5a-e but instead it is oxidized to copper(II) while the azides 5 are reduced by uptaking one electron per molecule and eliminating nitrogen. A probable explanation for the formation of the resulting copper(II) diisocyanate diamine complexes 8a, b (see Scheme 2) as well as the other reaction products is given. A mechanism involving a carbamoyl nitrene as well as a Curtius rearrangement can be excluded.

Notes: The hydroformylation of α-[2H]-styrene in the presence of an asymmetric rhodium-catalyst afforded two optically active isomeric aldehydes. The origin of the asymmetric induction is discussed on the basis of the chirality and the optical purity of the two products.

Notes: A Note on Methods for the Transformation of 1,2-Dicarboxylic Acids into α, β-Unsaturated Monocarboxylic Acids.A model study using the Diels-Alder adduct of maleic anhydride and butadiene (see scheme 3) exemplifies the conversion of the succinic acid type of structure into α, β-unsaturated carboxylic acids via two complementary fragmentations of 3,6-dioxo-perhydro-1,2-oxazine derivatives.