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Notizen: This paper discusses the hypothesis that insulin undergoes a conformational change either before or during its binding to the receptor. The evidence for this is not conclusive but allows us to reconcile the following observations: (1) no chemical modification or deletion of invariant surface residues has abolished the hormone's activity - only reduced its potency. (2) Reduction in potency follows many modifications to different side chains, both variant and invariant. (3) There are insulins with perfectly preserved structure (by the criteria of aggregation, spectroscopy, and x-ray analysis) that have markedly reduced potency. (4) Insulins with disturbed structure still exhibit real, sometimes substantial activity.

Notizen: We report here the refinement at 2.5-Å resolution of the x-ray crystal structure of bovine seminal ribonuclease, a dimeric covalent enzyme. The protein, which crystallizes with one molecule in the asymmetric unit, consists of two subunits of identical chemical sequences, related by an almost exact binary axis. The tertiary structure of the subunits is similar to that of the pancreatic enzyme, which shows similar catalytic properties. The refinement was carried out using the restrained least-squares procedure both in the reciprocal and real spaces. The assemblage of the subunits in the dimer is described and discussed.

Notizen: The clustering and internalization of epidermal growth factor (EGF)-receptor complexes on human tumor cells are temperature-sensitive processes that are completely inhibited at 4°C. The rotational diffusion of EGF-receptor is limited by the viscosity of the lipid matrix, while additional constraints limit the lateral diffusion of the receptor molecule. Although the lateral and rotational diffusion of the occupied receptors are temperature sensitive, they do not provide a rate-determining factor for the clustering and subsequent internalization of the EGF-receptor. Even at 4°C the occupied receptors move quickly enough to allow the formation of EGF-receptor clusters. The lack of internalization at 4°C must be due to the inhibition of interactions other than a temperature effect on receptor mobility. EGF-induced receptor clustering involves the formation of microclusters composed of 10-50 receptor molecules.

Notizen: Photochemically induced dynamic nuclear polarization was used to study the accessibility of surface tyrosine and tryptophan residues in proteinases, in their protein inhibitors and in the proteinase-inhibitor complexes. The accessibility probe is the triplet of 10-(carboxyethyl) flavin formed by optical excitation. On complex formation we observe accessibility loss in the surface tyrosines and tryptophans in the proximity of the proteinase-inhibitor contact site, and in the case of bovine pancreatic trypsin inhibitor, in more distant tyrosines as well.

Notizen: The β62.4- and β126.6-helical structures do not appear consistent with the structural data and ion-transport properties of (Ala-Ala-Gly) or (Leu-Ser-Leu-Gly) oligomers. Oligoalanine derivatives also give rise to current fluctuations in bilayer lipid membranes. Bundles of molecules may explain the behavior of these various peptides in membranes.

Notizen: The synthetic random polymers poly(Glu,Lys,Phe), poly(Glu,Phe) and poly(Glu,Lys,Tyr), have been used to study some parameters associated with the genetic control of the immune response (Ir) of mice. Mice of haplotypes d and q respond well to GLPhe. Mice of haplotypes k and b were previously shown to be nonresponders, whereas the F1 (k × b) responded via a phenomenon involving “complementation” between 2 Ir genes, i.e., one gene product from IA, and another from IE form the requisite two-chain Ia “receptor” macromolecules (EbβEkα). When it was determined that mice of haplotypes q and k respond to GPhe, and the controlling gene maps to IA, (Aα Aβ), we tested the theory that mice having q and k alleles in IA might respond to GLPhe via recognition of GPhe determinants in the terpolymer. Employing the in vitro proliferative response to T-cells from mice immunized with GLPhe and stimulated with GPhe and GLT (cross-reaction), it was determined that different determinant selection patterns exist in the recognition of GLPhe. Mice having q and k alleles in IA can respond to GLPhe via one mechanism, and other mice having d and f alleles respond via other mechanisms. The F1 of the appropriate nonresponder strains forming the Ia molecule (EbβEkα) still exhibit the “complementation” phenomenon. Rabbit antibody against anti-GPhe (ID) from SWR mice (H-2q)(anti-ID) was prepared. This anti-ID strongly inhibited the binding of 125I-GPhe by anti-GPhe antisera produced only in mice of H-2q haplotype and had no effect on the binding of GPhe by anti-GPhe antisera produced in mice of other haplotypes. The anti-ID also inhibited the binding of 125I-GLPhe and 125I-GPhe by anti-GLPhe antisera produced only in mice of H-2q haplotype. These specificities were also confirmed by the inhibition of the plaque-forming cells. It was concluded that the antibodies produced in mice of H-2q haplotype against GPhe and GLPhe share common idiotypic determinants that are recognized by the anti-idiotypic antiserum.

Notizen: The N-terminal maleoyl-β-alanyl derivative of human gastrin-[2-17] has been synthesized as a model compound to investigate the usefulness of such peptide derivatives for their mild and selective conjugation, via reaction with thiol groups, to high-molecular-weight carrier molecules to produce antigens, as well as to radioiodinable or fluorogenic molecules to prepare tracers for immunoassays. In this context the examined enzyme substrate-gastrin conjugate was found to exhibit the full immunoreactivity of the parent peptide and to be well suited as tracer in a gastrin fluorescence-immunoassay.

Notizen: Biocompatible, biodegradable copolymers of glutamic acid and ethyl glutamate were evaluated for their permeability to proteins ranging in molecular weight from 12,300 to 69,000. The results showed that the copolymers were sufficiently permeable that they could be used for the preparation of implantable, controlled-release systems capable of releasing therapeutic amounts of high-molecular-weight drugs.

Notizen: The geminal and vicinal 13C-31P coupling constants have been monitored, as a function of pH, for a series of uracil and cytosine 3′- and 5′-nucleotides with a ribose, arabinose, or 2′-deoxyribose sugar. Data were also obtained for two 3′,5′-diphosphates in the ribose and arabinose series. The geminal J(C5′-P5′) and J(C3′-P3′) couplings show only a small dependence on the ionization state of the phosphate, decreasing by 〈 0.5 Hz in the pH 5-7 range. For the ribose and arabinose 3′-nucleotides, the vicinal J(C4′-P3′) increase (up to 1.5 Hz) on secondary phosphate ionization in the pH 5-7 range, whereas their J(C2′-P3′) couplings decrease (up to 1.5 Hz) over the same pH range. In contrast for the 2′-deoxyribose molecules, both couplings decrease (∼0.5 Hz) on phosphate ionization. The titration curves provide information about the influence of the sugar on the conformation about the C3′—O3′ bond. Some conformational trends could be rationalized by consideration of the sugar-puckerdependent contact interactions between the 3′-phosphate and the substituents on the furanose ring.

Notizen: Studies on copolymerization kinetics of N-carboxyanhydride (NCA) of O-acetyl-L-tyrosine (T) with NCAs of L-valine (V) and glycine (G) were carried out in dioxane at 25°C with n-butylamine as initiator. The reactivity ratios for the VT system were found to be rV:rT:0.57:0.22; and for the GT system, rG:rT:0.26:0.42. A comparison of this data with that obtained when L-analine was used in place of L-valine or glycine showed that in the three systems, the reactivity ratio of the amino acid residue with a greater tendency to form ordered secondary structure was greater than that of its comonomer. Among the variable comonomers (glycine, L-alanine, L-valine) of O-acetyl-L-tyrosine, it is again L-alanine, whose tendency to form helical structure is very high, that has the greater reactivity ratio.

Notizen: We describe the synthesis and the conformational analysis by ir, CD, and proton-nmr spectroscopy of four model peptides of the type N-Ac-Tyr-X-His-NH2 with X = Val, Leu, Ala, Gly. These peptides represent the central sequence of the hormone angiotensin II and its position-5 analogs. We studied their conformational behavior in aqueous solution during pH titration and in organic solvents. For specific purposes of spectral analysis (ir band assignment, proton-nmr signal assignment, heteronuclear vicinal coupling constants), we synthesized three isotopically enriched homologs of the mother sequence, i.e., N-Ac-(15N-Tyr)-Val-His-NH2, N-Ac-(13C, 2H, Tyr)-Val-His-NH2, and N-Ac-Tyr-(13C, 2H, Val)-His-NH2. Results are summarized as follows: the tyrosine and the histidine side chains influence each other through space; this mutual influence is modulated by the nature of the side chain in position X and decreases in going from X=Val to X=Gly as a consequence of two simultaneous events, changes in the side-chain rotamer distribution and changes in the ϕ and ψ angles of residue X. The decrease in the bulkiness of the side-chain X (Val → Gly) leads to increased flexibility of the peptide backbone at this site, which is also reflected in the apparent ratio of C5, C7, and intermediate conformations present in equilibrium. The three spectroscopic techniques, in addition to the results of chymotryptic degradation experiments, show a high level of agreement, and all reflect the dynamic conformation of these peptides in a different manner.

Notizen: „We lehrt nun die Natur zu geben und zu empfangen? Es gibt der Kupfermensch, und es nimmt der Wasserstein; es gibt das Erz, und es nimmt die Pflanze; es geben die Sterne, und es nehmen die Blüten; es gibt der Himmel, und es nimmt die Erde.“ [Aus einem alchemistischen Traktat des Zosimos (um 400 n. Chr.) „Über die Kraft“ (Coll. des Alch. Grecs)]

Notizen: Experimente zur Lewis-Basizität: Ein Nikkelkomplex als Indikator für die Lösungsmittel-Basizität

Notizen: 13C-NMR. Spectra of Dicyanohydroquinones and Dicyano-p-benzoquinonesThe 13C-NMR. spectra of 12 dicyanohydroquinones and fully substituted dicyano- and diazido-p-benzoquinones have been measured and assigned by comparison with related benzene and p-benzoquinone derivatives. For p-benzoquinones the influence of the cyano and azido substituents on the chemical shift of the CO-, α- and β-C-atoms has been investigated.

Notizen: Thermal cyclization of the pyrimidine-N-oxide dicarbamate 2 gives a 95:5 mixture of the 2-oxo-2H-[1,2,4]oxadiazolo[2,3-a]- and [2,3-c]pyrimidinecarbamates 3 and 4. An efficient procedure for the conversion of 3 to 4, and vice versa, is described.

Notizen: Polarographic Investigations on Symmetrical Triazacarbocyanine Dyes in MethanolThe reduction mechanism of eleven symmetrical triazacarbocyanine dyes with different heterocycles in methanol (containing lithium chloride or lithium acetate/acetic acid) has been investigated by means of polarography, cyclic oscillopolarography and coulometry.The reduction occurs in a reversible to irreversible two electron transfer step, followed by an irreversible chemical step. Reduction potentials, transfer coefficients and specific currents have been measured and compared with properties measured in acetonitrile.The effect of substituents X has been studied on the compounds 1-ethyl-2-[3-(1-ethyl-6-X-1,2-dihydroquinolin-2-ylidene)-1-triazeno]-6-X-quinolinium tetrafluoroborate 1f(X) and 3-ethyl-2-[3-(3-ethyl-5-X-Δ4-1, 3-thiazolin-2-ylidene)-1-triazeno]-5-X-1, 3-thiazolium tetrafluoroborate 1g(X), and ρ-values of 0.20 and 0.40 V, respectively, have been found.

Notizen: The anion [(OH)3(O)AsCH2As(O)(OH)2] has been trapped in an X-irradiated single crystal of methylene diarsonic acid. The g-tensor and the hyperfine coupling tensors of the two 75As-nuclei have been obtained and the spin densities in the arsenic 4s- and 4p-orbitals determined.

Notizen: Excited singlet states of bicyclobutylene-benzene (2), 1,2:4,5-bis (bicyclo-butylene)benzene (3), 2,3-bicyclobutylene-naphthalene (4), and 1,8-bicyclobutylene-naphthalene (5) are investigated by means of linear dichroic absorption spectroscopy of molecules oriented in stretched polyethylene films and by semiempirical model calculations. The results indicate a strong hyperconjugative impact of the bicyclobutylene group on the aromatic chromophores in these compounds. Valence isomerization to aromatic products is predicted as the preferred photochemical pathway.

Notizen: The hydrogenation of 2′, 3′-O-isopropylidene-5-methyluridine (1) in water over 5% Rh/Al2O3 gave (5 R)- and (5 S)-5-methyl-5, 6-dihydrouridine (2), separated as 5′-O-(p-tolylsulfonyl)- (3) and 5′-O-benzoyl- (5) derivatives by preparative TLC. on silica gel and ether/hexane developments. The diastereoisomeric differentiation at the C(5) chiral centre depends upon the reaction media and the nature of the protecting group attached to the ribosyl moiety.The synthesis of iodo derivatives (5 R)- and (5 S)-4 is also described. The diastereoisomers 4 were converted into (5 R)- and (5 S)-2′, 3′,-O-isopropylidene-5-methyl-2, 5′-anhydro-5, 6-dihydrouridine (7).

Notizen: The Acylation of 5-Amino-1 H-1,2,4-triazoles. A 13C-NMR. StudyThe acylation of 3-substituted-5-amino-1 H-1,2,4-triazoles (1) with methyl chloroformate or dimethylcarbamoyl chloride yielded mainly 1-acyl-5-amino-1,2,4-triazoles (2 and 3). Acylation of 3-methyl-, 3-methoxy- and 3-methylthio-5-amino-1 H-1,2,4-triazole (1b, 1c and 1d) with methyl chloroformate gave up to 10% of the 1-acyl-3-amino-1,2,4-triazoles. For the unsubstituted 5-amino-1,2,4-triazole (1a), a (1:1)-mixture of the 3- and 5-isomers 2a and 4 was obtained in dioxane in the presence of triethylamine. No 4-acylated product was detected in contrast to earlier reports. The structures of the reaction products were determined with the aid of proton coupled 13C-NMR. spectra using the corresponding N-methyl-1,2,4-triazoles as reference compounds.

Notizen: The X-ray crystallographic molecular dimensions and thermal response of the 5, 13-diphenyl-cyclonoa [b]naphthalene 1a, are described.

Notizen: 7,7-Dimethyl-6-methylidenetricyclo[6.2.1.01,5]undec-9-ene (10) has been prepared from allylic alcohol 8 in one step in 16% yield. Selective hydrogenation of 10 with diazene gives the 2-norzizaenes 1a and 11.

Notizen: STO-3G calculations show that the nitrocyclopropyl anion prefers a triplet ground state with a tetrahedral C(α)-atom and a perpendicular orientation of the three-membered ring and the NO2-group, 1-90° (Table 1). This unusual result is in agreement with recent experimental findings of Kai et al. (Helv. Chim. Acta 65, 137 (1982)). Other NO2-anions as well as all CHO-, COOH- and CN-substituted anions 2-12, have singlet ground states 2-0°-12-0° (Table 1), in agreement with copious experimental data (Wagner & Boche, Z. Naturforsch. 37b, 1339 (1982)).

Notizen: A general method for enlargement of carbocyclic rings by the so called zip reaction is given. The Michael adducts of 2-nitrocycloalkanones with 3-oxo-4-pentenoates in the presence of tetrabutylammonium fluoride give in high yield compounds with the ring enlarged by four C-atoms. By this method 7-, 8-, and 12-membered cycloalkanones were converted respectively to 11-, 12-, and 16-membered functionalized carbocycles (see Scheme 2 and 3).

Notizen: Pure alkaline phosphatase (EC 3.1.3.1; 1500 U/mg) was dialyzed at 4° during 168 h against water, 10-4M EDTA or 10-4M o-phenanthroline. During the dialysis, samples were periodically removed and analyzed for metal content and activity. The results indicate that 1 mol of native calf intestinal alkaline phosphatase contains 4 g-atom of zinc and 4 g-atom of magnesium tightly bound, and that both metal ions are necessary for full enzyme activity. The dialyzed, partially demetallized enzyme could be reactivated by the addition of zinc and/or magnesium salts.

Notizen: Stereochemical Correlations between (2R,4′R,8′R)-α-Tocopherol, (25S,26)-Dihydroxycholecalciferol, (-)-(1S,5R)-Frontalin and (-)-(R)-LinalolThe optically active C5- and C4-building units 1 and 2 with their hydroxy group at a asymmetric C-atom were transformed to (-)-(1S,5R)-Frontalin (7) and (-)-(3R)-Linalol (8) respectively; 1 and 2 had been used earlier in the preparation of the chroman part of (2R,4′R,8′R)-α-Tocopherol (6a, vitamin E), and for introduction of the side chain in (25S,26)-Dihydroxycholecalciferol ((25S)-4), a natural metabolite of Vitamin D3. The stereochemical correlations resulting from these converions fit into a coherent picture with those correlations already known from literature and they confirm our earlier stereochemical assignments. A stereochemical assignment concerning the C(25)-epimers of 25,26-Dihydroxycholecalciferol that was in contrast to our findings and that initiated the conversion of 1 and 2 to 7 resp. 8 for additional stereochemical correlations has been corrected in the meantime by the authors [26].

Notizen: With a modification of the cyclization procedure of Richman & Atkins [8] the two macrocycles 1,4,7-tritosyl-11-benzyl-1,4,7,11-tetraazacyclotetradecane (8) and 1,7,11-tritosyl-4-trityl-1,4,7,11-tetraazacyclotetradecane (15) were prepared. After selective cleavage of the benzyl and trityl group, respectively, one obtains the two key products 1,4,7-tritosyl-11-benzyl-1,4,7,11-tetraazacyclotetradecane (9) and 1,7,11-tritosyl-4-trityl-1,4,7,11-tetraazacyclotetradecane (16) which have three N-atoms protected by tosyl groups and one accessible for further reactions.To test some of the possibilities we have alkylated 9 and 16 with iodoacetamide, 1-tosyl-aziridine and acrylonitrile. After detosylation with HBr in glacial acetic acid in the presence of phenol mono-N-functionalized tetraazamacrocycles were thus obtained. The advantage of this synthesis is that the cyclization which is the most difficult step of the whole procedure, has to be done only once, regardless of the nature of the pendant arm. In addition a large number of derivatives can be prepared by varying the alkylation component.With Ni2+, Cu2+ and Zn2+ metal complexes of these new ligands were prepared and their IR. and VIS. spectra studied. In the case of the carbamoyl derivatives 12, 14 and 18 the Cu2+-complexes exist in two forms. Whereas at low pH the carboxamide group of the pendant arm is probably not bound to the metal ion, at high pH after deprotonation it coordinates in one of the axial positions.

Notizen: Tentative Synthesis of ‘Bis(triasterane)’ and Synthesis of the Heterocyclic (Tricyclo[4.4.1.01,6]undeca-3,8-diene-11,11-dimethyl)sulfiteThe synthesis of the bis(triasterane) (1) has been tried; the reaction of ‘isotetraline’ (1,4,5,8-Tetrahydronaphthalene; 2) with diazomalonate yielded the tricyclic systems 5 and 6, and not 4. Hydrolysis of 5 gave the monocarboxylic acid 7, and not the dicarboxylic acid 9. The latter could be obtained from the dibromoderivative 8, but 9 couldn't be converted to the acyl chloride 10. The reduction of 9 with LiAlH4 yielded the crystalline diol 11, which was cyclized with SOCl2 to the heterocycle 12. The spectral data of the new compounds 5, 6, 7, 11 and 12 are reported and discussed.

Notizen: A detailed study of the biodegradation of one of the fish toxic chlorinated resin acids, 12,14-dichlorodehydroabietic acidThe correct IUPAC-name is 12,14-dichloro-8,9,11,12-tetradehydro-7,8-dihydroabietic acid. (3) is presented. When exposed to the fungus Mortierella isabellina, 3 is converted into a number of hydroxylated and keto derivatives which show low levels of toxicity to fish. These metabolites were isolated and characterized.

Notizen: Zero-current Ion-transport Studies and Potentiometric Measurements on Membranes Containing Chromoionophores for Li+ and UO22+Non-macrocyclic ionophores for Li+ and UO22+ have been substituted with a diphenylmaleimide unit. In membranes the obtained chromoionophores induce the same ion-selectivity and ion-transport behavior as the unsubstituted ligands.

Notizen: Reactivity-structure correlations for anisole and eleven of its substituted derivatives established from bromination rate constants in liquid SO2, unlike observations in water, show the reaction to be highly sensitive to substituent effects, (ρH2O+ = -7.1; ρSO2+ = -10.51). This result is ascribed to the solvation of the methoxy group which decreases the conjugation of para-substituted (ρO+ = -9.70) compared to that of ortho-substituted derivatives (ρP+ = -8.86). The highly solvated transition state lies far from reactants on the reaction coordinate and the positive charge developed in this state is nearly unity.

Notizen: Peptidic model conjugates carrying a single 2-carboxy-4,6-dinitrophenyl haptenic group, and as carbohydrate moieties D-gluconoyl, β-D-mannopyranosyl, 2-deoxy-β-D-glucopyranos-2-yl, or lactobionoyl residues, including the pseudocarbohydrate residue 1,3,4,5-tetrahydroxycyclohexane-1-carbonyl, were synthesized. Conjugates carrying the lactobionoyl of the bis(2-deoxy-β-D-glucopyranos-2-yl) moiety were anaphylactogenic in the guinea pig, passively sensitized against 2-carboxy-4,6-dinitrophenyl antigen.

Notizen: The stereochemical aspects of the intramolecular Ramberg-Bäcklund reaction, i.e. the 1,3-elimination of hydrogen halide followed by sulfur dioxide extrusion, have been studied on the α-bromosulfones of the 1-thiadecalinThroughout this paper ‘1-thiadecalin’ will be used in place of ‘decahydro-1-thianaphthalene’. series. Whereas the cis,exo-bromosulfone 23a containing the ideal W-type arrangement of the reacting atoms undergoes a clean Ramberg-Bäcklund reaction, the trans,exo- and trans,endo-bromosulfones, 24a and 24b, respectively, lead to an α,β-unsaturated sulfone by simple 1,2-elimination of HBr. Application of the Ramberg-Bäcklund reaction to 9-bromo-8-thiabicyclo[5.2.1]decane-8,8-dioxide (17) permits a short synthesis of the Bredt olefin bicyclo[5.1.1]non-1(8)-ene (5), which can be isolated but shows the typical high reactivity of other methylene-bridged (E)-cyclooctenes.

Notizen: Conversion of 2-bromomethylstyrene 22 and benzocyclobutenyl carbamate 28 to the benzophenanthridine alkaloids (±)-chelidonine (1, five steps, 25% from 28) and to (±)-norchelidonine (2, six steps, 24% from 28) are described. The key step 29 → 31 involves a highly regio- and stereocontrolled intramolecular Diels-Alder reaction of the (E)-quinodimethane 30.

Notizen: Dehydrogenation of hydroaromatic compounds with quinones was reinvestigated in the light of recent criticism of the reaction mechanism. Kinetic and spectroscopic evidence shows that disappearance of substrate proceeds at the same rate as the product-forming step. A mechanism consisting in fast formation followed by slow decomposition of an intermediate can be ruled out. The order of reactivities of 1,4-cyclohexadiene (1), 1,4-dihydronaphthalene (8) and 9,10-dihydroanthracene (11) changes in going from benzoquinone to chloranil or 2,3-dichloro-5,6-dicyanobenzoquinone. It is suggested that this behaviour could be due to contribution of CT-complexes or HOMO-LUMO interactions for determining the reactivity of the substrates.

Notizen: Dependence of the Stereoselectivity on the Leaving Group, the Temperature and the Solvent in the Favorskii-Reaction of Enolisable CyclobutanonesThe base-induced contraction of enolisable 2-halocyclobutanones is often not stereoselectiv. The cis/trans-isomer ratio in the cyclopropanecarboxylic acid 9 derived from 2,4-cis-substituted cyclobutanones 7 depends on the nature of the leaving group. In addition, the choice of the base, the temperature and the solvent can profoundly affect the stereoselectivity of the Favorskii-reaction. The use of the p-bromophenylsulphonyloxy group as leaving group and an inhomogenous reaction medium leads exclusively to cis-carboxylic acid 9.

Notizen: Synthesis of Glyceryletherphosphatides, 2nd Communication. Preparation of 2-O-Acetyl-1-O-[(Z)-9-octadecenyl]-sn -glyceryl-3-phosphorylcholin (‘Oleyl-PAF’), of its Enantiomer and Some Analogous, Unsaturated CompoundsSyntheses of the unsaturated glyceroletherphospholipid 1a as an olefin-analog of ‘Platelet Activating Factor’ (PAF) are described together with the methods for the preparation of the enantiomer 1′a, the corresponding ‘lyso compounds’ 1b and 1′b and their positional isomers 21a, 21′a, 26, 26′, 25, 25′ obtained on formally exchanging the attachment site of the functional groups at the glycerol moiety. Structural assignments and optical purity of the compounds are confirmed.

Notizen: Three macrocyclic polyamines [24]ane-N6 1, [32]ane-N8 2 and [27]ane-N6O3 3 of ring size 24, 32 and 27, respectively, have been synthesized. They contain either trimethylenediamine of ethylenediamine units. The acyclic analog 4, as the reference compound, was also prepared. Compounds 1-3 are macrocyclic analogs of natural polyamines and are potential ligands for metal cations as well as, when protonated, for anions. The protonation constants of compounds 1-4 have been determined. They are high enough for compounds 1-4 to be fully protonated in a pH-range close to neutrality, as required for binding of anions of weak acids. The effect of structural features on the protonation constants are briefly discussed in relation to the design of macrocyclic polyamine ligands.

Notizen: Irradiation (λ〉280 nm) of 3-hydroxypyrroles 1 in acetonitrile leads to the formation of 3,3′-bi-3H-pyrroles 2 in reasonable to good yields.

Notizen: On the Course of the Intramolecular Diels-Alder-Reaction of Cyclopentadienes with Olefinic SubstituentsThe 1:3 mixture of 4-bromobicyclo [3.2.0]hept-2-en-6-one and -7-one (1/2), available by N-bromosuccinimide bromination of bicyclo [3.2.0]hept-2-en-6-one, reacted rapidly with the organo-magnesium and -zinc reagents 3, 10a, 10b and 10d by cyclobutanone ring opening and bromide ion expulsion to give the 5-substituted cyclopentadienes 5, 12a, 12b/12c, and 12d as non-isolated intermediates. Further transformation occured in situ either by a direct intramolecular Diels-Alder reaction (path a) or by a [1,5]-H-migration prior to the intramolecular Diels-Alder reaction (path b). The intermediate 5 followed only path a to give the bridged norbornene derivative 7, the intermediates 12a, 12b and 12c followed only path b to give the annellated norbornene derivatives 15a, 15b and 15c, respectively, and the intermediate 12d followed both paths to give the bridged 14d and the annellated norbornene derivative 15d (in the ration of about 1.4:1). These observations are discussed in terms of the relative velocities of [1,5]-H-migrations and intramolecular Diels-Alder reactions. The major conclusions are: (1) bridged norbornene derivatives with a six-membered ring C (such as 14d) can be prepared by an intramolecular Diels-Alder reaction from 5-alkenyl-cyclopentadienes 12, as long as the dienophilic double bond is activated by an appropriate substituent (as in 12d); (2) such 5-alkenyl-cyclopentadienes 12 are available from the reaction of the bromo-bicyclo-heptenones 1/2 with suitable C-nucleophiles 10.

Notizen: Spiro 3-Oxazolines from the 1,3-Dipolar Cycloaddition of Benzonitrilio-2-propanide and 1,4-QuinonesOn irradiation with light of wavelength 290-350 nm, 2,2-dimethyl-3-phenyl-2H-azirine (1b) reacts with 1,4-naphthoquinone to give the 1H-benzo [f]isoindol-4,9-dione (11) (Scheme 3) via cycloaddition of the benzonitrilio-2-propanide (2b) onto the quinone C, C-double bond. With 2-methyl- and 2,3-dimethyl-1,4-naphthoquinone, the nitrile ylide 2b undergoes cycloaddition preferentially onto the C, O-double bond of the quinone, leading to spiro-oxazolines 12 and 14 (Scheme 4). Steric as well as electronic effects can be discussed to explain the observed site selectivity of the cycloaddition.With the 1,4-benzoquinones 15a, 15b, 15d and 15f, nitrile ylide 2b undergoes the 1,3-dipolar cycloaddition exclusively onto the C, O-double bond. The corresponding spiro-oxazolines have been isolated in 17-32% yield. This contrasts with the previously reported results with benzonitrilipo-phenylmethanide (2a), which undergoes cycloaddition to the C, C-double bond of 1,4-benzoquinones (cf. [1]). This difference in the site selectivity of the 1,3-dipolar cycloaddition can be explained with Houk's concept of LUMO-polarization, that is, the stronger nucleophilic dipol 2b polarizes the LUMO of a α,β-unsaturated carbonyl compound more efficient than the less nucleophilic 2a. This leads to a preference of the cycloaddition to the C, O-double bond in the case of 2b.With 2,3-dimethyl- (15c) and 2,3,5,6-tetramethyl-1,4-benzoquinone (15e), nitrile ylide 2b undergoes C, O- as well as C, C-cycloaddition (Schemes 7 and 8).

Notizen: About the Availability of 13C-NMR Substituent Increments in 1,4-Benzo- and 1,4-NaphthoquinonesThe 13C-NMR spectra of a number of substituted 1,4-benzo- and 1,4-naphthoquinones have been obtained and assigned. Effects of CH3-, O-alkyl-, Cl-, NH2- and N3- substituents have been deduced for the quinoid part of the molecules and used for the calculation of 13C-chemical shifts.

Notizen: Flow thermolysis of 2-propynyl propiolate (5) at 580° afforded butatriene (6) (ca. 50%) and, as by-products, 4-methylene-2-cyclobuten-1-one (7), 2-ethynylpropenal (8), 1-penten-4-yn-3-one (9), 4-penten-2-ynal (10) (total ca. 10%), along with some propynal, acetylene, CO2 and CO. In the same way, propiolic acid (1,1-D2)-2-propynyl propiolate (11) led to (1,1-D2)-butatriene (12) and a little 4-((D2)methylene)-2-cyclobuten-1-one (13). A mechanism is proposed for the transformation of 5 into 6 and of 11 into 12, which also accounts for the formation of 7,8,9 and 10, as well as 13. The position of one of the published 13C-NMR signals of butatriene (6) must be revised. Thermolysis of methyl-(1) and ethyl propiolate (2) resulted in small yields of 2-buten-4-olide (3) and 2-penten-4-olide (4).

Notizen: 13C-NMR. Substituent Increments of the Azido-group in 1,4-BenzoquinonesThe empirical substituent increments of the azido-group in 1,4-benzoquinones have been derived from the 13C-NMR. chemical shifts of 2-azido-5-chloro-1,4-benzoquinone. The validity of the obtained values was tested by comparison of the empirical and computed 13C-NMR. chemical shifts of other azido-chloro-1,4-benzoquinones.

Notizen: The synthesis of a large variety of enantiomerically pure substituted reactive cyclopentenes 16, 23, 24 and 28 have been synthesized from the readily available (-)-quinic acid 1. The straightforward strategy involves a high-yielding intramolecular aldolization-dehydration of acyclic 1,6-dialdehydes 13, 18, 19 and 27 obtained by oxidative cleavage of cyclohexanediols 5, 7, 11 and 12, using either lead tetraacetate or triphenylbismuth carbonate. Neither sulfoxide formation nor racemization of the intermediate dialdehydes at the oxygenated chiral centre was observed. Transformation of the thioacetal 25 to the corresponding ketone 26 using phenylselenic anhydride is also described.

Notizen: Photochromism of spiropyrans. Photodegradation of aza-, oxaza-, and thiaza-cyclopentane- and -cyclohexanespiropyransStudy of the photodegradation of saturated azaheterocyclic spiropyrans showed that electron-donor substituents improve, as in the benzoheterocyclic series, the fatigue properties towards. UV. light. The introduction of oxygen or sulfur in the 5- or 6-membered saturated azacycles or the substitution with an orthofused aromatic nucleus have practically no influence on the results of photodegradation. The indolinospiropyrans allow the greatest number of photochromic cycles before falling to half the initial absorbance on photolysis under accurate conditions.

Notizen: Low-Temperature 13C-NMR. Spectroscopy of Organolithium Derivatives. - 13C, 6Li-Coupling, a Powerful Structural InformationThe 13C-NMR. spectra of thirteen lithiated hydrocarbons (1c-13c. Table 2) and of eighteen a-halo-lithium carbenoids (14c-31c, Table 3) have been recorded in donor solvent (R2O, R3N) mixtures at temperatures down to -150°. The organolithium species were generated from singly or doubly 13C-labelled precursors by H/6Li- or Br/6-exchange. - 13C, 6Li-Coupling was observed of all species but those which supposedly contain contact ion pair C,Li-bonds (benzylic and acetylenic derivatives). The multiplicities of the signals are correlated with the degree of aggregation in solution: the triplets of the halocarbenoids must arise from monomers or heteroatom-bridged oligomers, the quintuplets of butyl-, cyclopropyl-, bycyclo[1.1.0]butyl-, vinyl-, and phenyllithium from dimers with planar arrangement of two Li- and two C-atoms, as known from crystal structures (Scheme 3). All 13C, 6Li-couplings are temperature-dependent, dynamic processes cause them to disappear above ca. -70° (Fig. 1-4). - Types of organolithium compounds are categorized according to the change of chemical shift δΔ (H, Li) upon H/Li-substitution, according to the 13C, 6Li-coupling constants ranging from 0 to 17 Hz, and according to the multiplicities which indicate the aggregation: type A are Li-derivatives of alkanes and cycloalkanes, type B are s̰-bonded vinyl, aryl, and alinyl derivatives, type C are a-heterosubstituted (RS, hetero=halogen) organolithium compounds, and type D are π-bonded allylic and benzylic systems (Table 5). The C,Li-distances in the crystal structures of representatives of all four classes are within the small range of 2.18-2.28 Å (cf. Scheme 3). - Some surprising observations and their interpretations and consequences are: (a) butyllithium solutions in THF, THF/TMEDA, and dimethyl ether contain increasing amounts of dimer upon cooling, the equilibrium (tetramer · 4 THF)+4 THF ⇌ 2 (dimer · 4 THF) being shifted to the right (Fig. 1 and Scheme 4); thus, more of a different species is present at low temperatures, with the accompanying changes in reactivity; (b) mixed higher aggregates are formed upon addition of butyllithium to bicyclobutyllithium; these are broken up to dimers upon addition of TMEDA (Tetramethylethylene-diamine) (Fig. 2 and Scheme 5); (c) the solid state, the calculated gas-phase and the solution species of phenyllithium all have dimeric structures, and so do vinyl and cyclopropyl lithium derivatives; the 13C-deshielding observed upon replacement of H by Li on sp2- and sp-C-atoms is related to a polarization of the π-electrons (Table 3, Fig. 3 and Scheme 6); (d) the spectra of halo-lithium carbenoids show three striking features as compared to the C,H-compound: deshielding of up to 280 ppm (Table 3), strong decrease of the coupling constant with 1H- and 13C-nuclei attached to the carbenoid C-atom (Table 4), and a structure-independant, almost constant, large 13C, 6Li-coupling constant of 17 Hz (Table 3); as shown in Scheme 7, these effects might be the consequence of a reduced degree of hybridization of the carbenoid C-atom. - The preparation of the labelled compounds and the generation of solutions of the organolithium compounds for NMR. measurements are described in full detail.

Notizen: From treatment of D-labelled 1, 2exo-, 1, 2endo- and 2endo, 6endo-trimethylene-norbornane (1, 2 and 3, resp.) with aluminum bromide in carbon disulfide, the evidence is gained that a degenerate rearrangement is involved in the admantane rearrangement of both 1 and 2 to 3.

Notizen: The 1,3-dipolar cycloaddition of the C-t-butyloxycarbonyl-N-mannosyl-nitrone 5, formed in situ from the partially protected D-mannose-oxime 3 and the glyoxylate 4, to ethylene gave preferentially the (3S)-N-glycosyl-isoxazolidine 6 which was transformed into the 3-isoxazolidine-carboxylate (L-5-oxaproline ester) 12 and into some derivatives thereof. The (S)-configuration of 12 was proved by chemical correlation with a derivative of L-asparagine. The D-5-oxaproline ester was obtained from the corresponding N-ribosyl-nitrone 24. Two protected dipeptides containing either C-terminal- (28) or N-terminal-5-oxaproline (= Opro) (30) were synthesized. Starting from 12, the analogue 1 of captopril® (2) was prepared and its activity as an inhibitor of the angiotensin-converting-enzyme (ACE) was examined.

Notizen: (3S, 8E)-1,3-Dihydroxy-8-decen-5-one, a Metabolite of Streptomyces fimbriatus (MILLARD and BURR 1926)From the cultures of Streptomyces fimbriatus, strain Tü 2335, the title compound 1 was isolated by solvent extraction, chromatography, and distillation. Its constitution was determined by spectroscopic investigations of 1 and some of its derivatives, and the chirality by transformation to (R)-1,3-isopropylidenedioxy-decane (12); a reference sample of the latter was prepared from (R)-methyl 3-hydroxydecanoate (10). In the equilibrium mixture the keto form 1 predominates the two hemiacetals 2a and 2b. Compound 1 is inactive against bacteria, yeasts and fungi.

Notizen: (Phenacetin)4·2I4·2H2O is triclinic, a = 13.641 (7), b = 12.807 (6), c = 7.201 (3) Å, α = 99.8 (4), b̃ = 86.5 (4), γ = 104.0 (5)°, P1, Z = 1. The ordered crystal structure has been refined to RF = 0.050, using 4173 independent reflections measured on a four-circle diffractometer with MoKa (graphite monochromator) radiation. The crystals are composed of alternating positively and negatively charged slices; each positive slice contains a double layer of stacks of hemi-protonated phenacetin molecules which are H-bonded through their carbonyl groups (d(O - - - O) = 2.432 (4) Å) while each negative slice contains a single layer of I2-4-ions linked in chains along [100] through H-bonds to pairs of water molecules. The axes of the phenacetin stacks are parallel to the planes of the (I2-4·2H2O)-layers. The I2-4-ion is centro-symmetric and can be approximately represented as I-- - - I-I- - - I- (d(I- - - - I) = 3.404 (1) Å; d(I-I) = 2.774 (1) Å). The compound is a pseudo-type A basic salt.

Notizen: The influence of steric compression on electronic structure in polycyclic olefinic alcohols and amines is studied by PE. spectroscopy.The unsubstituted alcohol 2 and amine 7 show PE.-spectroscopic properties that can be reconciled by postulating a predominance of intramolecularly H-bonded species in the gas phase.For the alkylated derivatives 5 and 9, in which H-bonding is precluded, distinct, but only moderate lone-pair double-bond interactions are observed.

Notizen: The [2.2.2]hericene (6), a bicyclo[2.2.2]octane bearing three exocyclic s-cis-butadiene units has been prepared in eight steps from coumalic acid and maleic anhydride. The hexaene 6 adds successively three mol-equiv. of strong dienophiles such as ethylenetetracarbonitrile (TCE) and dimethyl acetylenedicarboxylate (DMAD) giving the corresponding monoadducts 17 and 20 (k1), bis-adducts 18 and 21 (k2) and tris-adducts 19 and 22 (k3), respectively. The rate constant ratio k1/k2 is small as in the case of the cycloadditions of 2,3,5,6-tetramethylidene-bicyclo [2.2.2]octane (3) giving the corresponding monoadducts 23 and 27 (k1) and bis-adducts 25 and 29 (k2) with TCE and DMAD, respectively. Constrastingly, the rate constant ratio k2/k3 is relatively large as the rate constant ratio k1/k2 of the Diels-Alder additions for 5,6,7,8-tetramethylidenebicyclo [2.2.2]oct-2-ene (4) giving the corresponding monoadducts 24 and 28 (k1) and bis-adducts 26 and 30 (k2). The following second-order rate constants (toluene, 25°) and activation parameters were obtained for the TCE additions: 3+TCE→23: k1 = 0.591±0.012 mol-1·l·s-1, ΔH≠=10.6±0.4 kcal/mol, and ΔS≠ = -24.0±1.4 cal/mol·K (e.u.); 23+TCE→25: k2=0.034±0.0010 mol-1·l·s-1, ΔH≠ = 10.6±0.6 kcal/mol, and ΔS≠ = -29.7±2.0 e.u.; 4+TCE→26: k1 = 0.172±0.035 mol-1·l·s-1, ΔH≠ 11.3±0.8 kcal/mol, and ΔS≠ = -24.0±2.8 e.u.; 24+TCE→26: k2 = (6.1±0.2)·10-4 mol-1·l·s-1, ΔH≠ = 13.0±0.3 kcal/mol, and ΔS≠ = -29.5±0.8 e.u.; 6+TCE→17: k1 = 0.136±0.002 mol-1·l·s-1, ΔH≠ = 11.3±0.2 kcal/mol, and ΔS≠ = -24.5±0.8 e.u.; 17+TCE→18: k2 = 0.0156±0.0003 mol-1·l·s-1, ΔH≠ = 10.9±0.5 kcal/mol, and ΔS≠ = -30.1 ± 1.5 e.u.; 18+TCE→19: k3=(5±0.2) · 10-5 mol-1 mol-1 ·l·s-1, ΔH≠ = 15±3 kcal/mol, and ΔS≠ = -28 ± 8 e.u. The following rate constants were evaluated for the DMAD additions (CD2Cl2, 30°): 6+DMAD→20: k1 = (10±1)·10-4 mol-1 · l·s-1; 20+DMAD→21: k2 = (6.5±0.1) · 10-4 mol-1 ·l·-1; 21+DMAD→22: k3 = (1.0±0.1) · 10-4 mol-1 ·l·s-1.The reactions giving the barrelene derivatives 19, 22, 26 and 30 are slower than those leading to adducts that are not barrelenes. The former are estimated less exothermic than the latter. It is proposed that the Diels-Alder reactivity of exocyclic s-cis-butadienes grafted onto bicycle [2.2.1]heptanes and bicyclo [2.2.2]octanes that are modified by remote substitution of the bicyclic skeletons can be affected by changes inthe exothermicity of the cycloadditions, in agreement with the Dimroth and Bell-Evans-Polanyi principle.Force-field calculations (MMPI 1) of 3, 4, 6 and related exocyclic s-cis-butadienes as a moiety of bicyclo [2.2.2]octane suggested single minimum energy hypersurfaces for these systems (eclipsed conformations, planar dienes). Their flexibility decreases with the degree of unsaturation of the bicyclic skeleton. The effect of an endocyclic double bond is larger than that of an exocyclic diene moiety.

Notizen: Attempted Synthesis of Push-Pull DiacetylenesTwo alternative synthesis of push-pull diacetylenes of type 1 (5-amino-2,4-alkadiynals) are investigated. A bromination-dehydrobromination sequence starting with 5-dimethylamino-2,4-pentadienal (2) as well as the application of the well-known Cadiot-Chodkiewicz coupling reaction give new intermediates 3-5, and 7 and 8, respectively, but fail to give the target molecules 1.

Notizen: Ring Transformations of 3-Substituted 5-Trifluoromethyl-1,3,4-thiadiazol-2(3H)-one with NucleophilesThe 3-chlormethyl-5-trifluoromethyl-1,3,4-thiadiazolone 3 undergoes a ring transformation to 3-acylated 2,3-dihydro-1,3,4-thiadiazoles 4 with many nucleophiles. Upon formal replacement of the chloromethyl group in the 3-position of 3 by an extended bromoalkyl chain (→9a-c), the reaction with nucleophiles yields 4-acylated 5,6-dihydro-4H-1,3,4-thiadiazines 10 (from 9a), 4,5,6,7-tetrahydrothiadiazepines 13 (from 9b) and 5,6,7,8-tetrahydro-4H-1,3,4-thiadiazocines 14 (from 9c) by ring enlargement. The 3-propargyl-thiadiazolone 17 rearranges with nucleophiles to 4-acylated 6-methylidene-5,6-dihydro-4H-1,3,4-thiadiazines 18. The structures of the new compounds were elucidated by 1H- and 13C-NMR spectroscopy.

Notizen: On the Mechanism of the α-Alkynone Cyclization: Synthesis and Thermolysis of 1-(1-Methylcyclopentyl)[3-13C]prop-2-ynoneThe relative migratory aptitude of two acetylenic substituents in the α-alkynone cyclization, a thermal conversion of α-acetylenic ketones A to 2-cyclopentenones C, was investigated by isotope-labeling experiments. The α-alkynone [β-13C]-1, specifically labeled with 13C at the β-acetylenic C-atom C(3), was synthesized by an intramolecular Witting reaction (230-300°) of the diacylmethylidenephosphorane [13C]-7. The latter resulted from acylation of methylidenetriphenylphosphorane with the acid chloride 4 to yield the acylmethylidenephosphorane 5, which in turn was formylated with acetic [13C]formic anhydride ([13C]-6.) Upon thermolysis of [β-13C]-1, its label at C(β) was transferred almost exclusively to C(β) of the 2-cyclopentenone moiety in the resulting cyclization product [13C]-2. We conclude that there is a distinct preference for hydrogen migration in the acetylene → alkylidene carbene isomerization (A → B) which precedes the cyclization step (B → C). No evidence was found for a fast reversibility of this isomerization (A ⇄ B) involving both acetylenic substituents.

Notizen: The Synthesis of 2,3,4,5-1H-Tetrahydroimidazo[2,1-b]quinazolin-2,5-diones and analogous 2,3,4,5-1H-Tetrahydroimidazo[1,2-a]thieno[2,3-d] (or [3,2-d])-pyrimidin-2,5-dionesThe syntheses of various imidazo [2, 1-b]quinazolinediones and their thiophene analogs are described.

Notizen: A conformational study was carried out on Boc-(L-Val-D-Val)6-OMe in the crystalline state by X-ray and IR. and by 1H-NMR. in chloroform. The dodecapeptide crystallizes from CHCl3/EtOAc with a left-handed helical structure of the type ↑↓ β5.6, and from CHCl3/MeOH (or MeOH) with a different structure. In chloroform it forms three slowly interconverting species: one is a ↑↓ β5.6 left-handed helical species, and the other two are most likely single-stranded β4.4 helical species of opposite handedness. The double-stranded helical species is predominant in fresh solutions of samples obtained from CHCl3/EtOAc. Because of the slow conversion or formation of this species some hours are needed to reach the conformational equilibrium in chloroform at 25°.

Notizen: Reaction of cobaltocene with cyclopentadiene and air results in the formation of the title compound; its structure has been elucidated by spectroscopic and X-ray methods.

Notizen: Synthesis of ‘Push-Pull’ DiacetylenesThe first synthesis of push-pull diacetylenes of type 1 is described. Reaction of perchlorobutenyne (8) with two equivalents of dialkylamine, followed by dechlorination using two equivalents of butyllithium gives lithio-dialkylamino-diynes 7. Final acylation of these intermediates leads to push-pull diacetylenes 1b-1e in good yields. The method allows the introduction of both push and pull substituents in a simple one-pot-procedure. In addition, 1a is prepared by hydroxymethylation of lithio-morpholino-diyne 7c, followed by oxidation with manganese dioxide in acetone.

Notizen: The 31P{1H}-NMR characteristics of the complexes [HgX2(1)] and [HgX2-(PPh2Bz)2] (X = NO3, Cl, Br, I, SCN, CN) and the solid state structures of the complexes [HgCl2(1)] and [HgI2(1)] (1 = 2,11-bis (diphenylphosphinomethyl)benzo-[c]phenanthrene) have been determined.The 1J(199Hg, 31P) values increase in the order CN 〈 I 〈 SCN 〈 Br 〈 Cl 〈 NO3. The two molecular structures show a distorted tetrahedral geometry about mercury. Pertinent bond lengths and bond angles from the X-ray analysis are as follows: Hg—P = 2.485(7) Å and 2.509 (8) Å, Hg—Cl = 2.525 (8) Å and 2.505 (10) Å, P—Hg—P = 125.6(3)°, Cl—Hg—Cl = 97.0(3)° for [HgCl2(1)] and Hg—P = 2.491 (10) Å and 2.500(11) Å, Hg—I = 2.858(5) Å and 2.832(3) Å, P—Hg—P = 146.0(4)°, I—Hg—I = 116.9(1)° for [HgI2(1)]. The equation, derived previously, relating 1J(199Hg, 31P) and the angles P—Hg—P and X—Hg—X is shown to be valid for 1.

Notizen: Ligand substitution reactions on square-planar platinum (II) complexes of the types trans-[PtRXL2], trans-[PtR(4-PADA)L2][BF4], trans-[PtRX() and trans-[PtR(4-PADA)()][BF4] R=H, Me; X=Cl-, I-; L=PEt3, bis(3-trifluoromethyl-phenyl)benzylphosphine (4), =the trans-spanning 2,11-bis[bis(3-trifluoro-methylphenyl)phosphinomethyl]benzo [c]phenanthrene (3); 4-PADA (=pyridine-4-azo-4′-(N, N-dimethyl)aniline have been studied at 30° using stopped-flow and conventional spectrophotometry, methanol as solvent, and 2.5 × 10-2 M ionic strength (LiClO4 as supporting electrolyte). 4-PADA was used as indicator ligand, as its absorption spectrum differs from those spectra where it is complexed.The expected steric effects of the bulky ligands, especially of 3, on the rates and mechanisms of all the reactions studied are small. All reactions take place by the usual two-term rate law. Noteworthy, for the complexes with the bulky ligands 3 and 4, the direct reaction path with the entering nucleophile is predominant. There is no preference for a solvent or dissociative path. The reactivity order for the hydride complexes is trans-[PtHX (PEt3)2]〈trans-[PtHX(4)2]〈trans-[PtHX (3)]. However, for the corresponding methyl complexes, there is some retardation by ligand 3, probably due to an interaction between the methyl group and the hydrocarbon moiety of 3, which inhibits the fluxional behavior of this ligand. The results have some relevance for the understanding of olefin-insertion reactions of hydride complexes containing these phosphine ligands.

Notizen: 5-Substituted 1,3,4-thiadiazol-2(3H)-ones were shown to exist almost exclusively in the oxo tautomeric form with the aid of proton-coupled 15N-NMR spectra using the corresponding 3-methyl-1,3,4-thiadiazol-2(3H)-ones and 5-substituted-2-methoxy-1,3,4-thiadiazoles as reference compounds.

Notizen: Reactions of 2,4,6-trimethylbenzenediazonium (1), 2,6-diethylbenzenediazonium (2) and 2,6-diisopropylbenzenediazonium (3) tetrafluoroborates were studied in magic acid, SbF5/SO2ClF, acetonitrile and acetone by 1H-NMR and by analysis of the dediazoniation products. The Nα-Nβ rearrangement of β-N15-labelled tetrafluoroborates 1-3 was followed by 15N-NMR of the corresponding arylazonaphthols, as well as by MS analysis of the anilines obtained by reduction of the azo compounds. Diazonium salts 2 and 3 were synthesized for the first time and the steric effect of substituents at C(2) and C(6) on the reactions under study is discussed. All the results obtained can be rationalized by heterolytic dediazoniation of diazonium salts 1-3 and product formation from the corresponding aryl cations.

Notizen: The evaluation of the dediazoniation kinetics of various m- and p-substituted benzenediazonium tetrafluoroborates in 1,2-dichloroethane at 50° in the presence of 18-crown-6, 21-crown-7 and dicyclohexano-24-crown-8 demonstrates that the rate constant for the dediazoniation within the complex (k2) is smallest, and the equilibrium constant for complex formation (K) is largest for the complexes with 21-crown-7 (cf. Scheme 1). The logarithms of the equilibrium constants (K) for complex formation with each of the crown ethers studied correlate well with Hammett's substituent constants, σ, to give reaction constants ρ = 1.18-1.38.A linear correlation between the logarithms of the rate constants for the dediazoniation within the complex with those of the dediazoniation rate constants of uncomplexed diazonium ions (log k2 vs. log.k1), found for most substituted diazonium salts, indicates that the dediazoniation mechanism of the complexed diazonium ions is not significantly different from that of the free ions. For very electrophilic diazonium ions (p-Cl, m-CN), k2 was much larger than expected on the basis of the linear log k2 vs. log k1 relationship. Analysis of the dediazoniation products showed that this was due to a change in mechanism from heterolytic to homolytic dediazoniation.The complexation rate of diazonium salts by crown ethers (kc) is practically diffusion controlled and does not change much with the size of the crown ether. The decomplexation rate (kd), however, is significantly lower for complexes with 21-crown-7, than for those with 18-crown-6 and dicyclohexano-24-crown-8, and is therefore the reason for the variations in the equilibrium constant (K) and thus for the fact that complexes of arenediazonium salts with 21-crown-7 are the most stable.The amounts of the Nα-Nβ rearrangement, as well as those of the exchange of the 15N-labelled diazonio group with external nitrogen during dediazoniation of p-toluenediazonium salt were independent of the addition of crown ethers.A dediazoniation mechanism involving a charge transfer, as well as an insertion-type diazonium ion-crown ether complex is proposed. In this mechanism, dediazoniation of the insertion complex does not take place directly, but through the charge-transfer complex.

Notizen: Oxidation of sulfides with PhIO/RuCl2 (PPh3)3 leads to sulfones. Electronwithdrawing substituents in the aromatic ring of PhIO reduce the reactivity and improves selectivity of the system. Thus, with m-iodosylbenzoic acid sulfides are converted to sulfoxide. Under the same conditions aliphatic primary alcohols are transformed to aldehydes with m-iodosylbenzoic acid, while PhIO affords carboxylic acids.

Notizen: The thujone-derived enone 1 is converted via enol lactone intermediates 4 and 5 to the optically active steroidal analogue 13 and the corresponding 19-norsteroid analogue 14. The structure of 13 was determined by X-ray diffraction analysis. The acid-catalyzed cyclopropane-ring opening of 13 and ozonolysis of the resulting olefin provided the 16-keto-steroid analogue 18.

Notizen: Conduction band electrons produced by band gap excitation of TiO2-particles reduce efficiently thiosulfate to sulfide and sulfite. \documentclass{article}\pagestyle{empty}\begin{document}$ {\rm 2e}_{{\rm cb}}^ - ({\rm TiO}_{\rm 2}) + {\rm S}_{\rm 2} {\rm O}_3^{2 - } \longrightarrow {\rm S}^{2 - } + {\rm SO}_3^{2 - } $\end{document}This reaction is confirmed by electrochemical investigations with polycrystalline TiO2-electrodes. The valence band process in alkaline TiO2-dispersions involves oxidation of S2O32- to tetrathionate which quantitatively dismutates into sulfite and thiosulfate, the net reaction being: \documentclass{article}\pagestyle{empty}\begin{document}$ 2{\rm h}^{\rm + } ({\rm TiO}_{\rm 2}) + 0.5{\rm S}_{\rm 2} {\rm O}_{\rm 3}^{{\rm 2} - } + 1.5{\rm H}_{\rm 2} {\rm O} \longrightarrow {\rm SO}_3^{2 - } + 3{\rm H}^{\rm + } $\end{document}This photodriven disproportionation of thiosulfate into sulfide and sulfite: \documentclass{article}\pagestyle{empty}\begin{document}$ 1.5{\rm H}_{\rm 2} {\rm O } + 1.5{\rm S}_{\rm 2} {\rm O}_{\rm 3}^{{\rm 2} - } \mathop \to \limits^{h\nu} 2{\rm SO}_3^{2 - } + {\rm S}^{{\rm 2} - } + 3{\rm H}^{\rm + } $\end{document} should be of great interest for systems that photochemically split hydrogen sulfide into hydrogen and sulfur.

Notizen: A general scheme for the synthesis of the tetrahydroisoindolinone moiety of naturally occurring cytochalasans and unnatural analogs was developed. The key-step consists of the intermolecular [2+4]cycloaddition of 4-methylsorbinol (7) to an alkylidene malonic ester derivative such as 6, 9 or 10, obtained from the corresponding amino acids. The products obtained, 4a, 17, and 18 were converted to the desired lactams 5, 21, and 22.Cycloaddition of the diene alcohol 7 to the optically active alkylidene malonic ester derivative 9b (s. Footnote 5) prepared from L-leucine gave compound 17b with 98% enantiomeric excess. The optical activity was retained during the conversion of 17b to the lactam 21b. The latter is a subunit for the synthesis of the aspochalasins.

Notizen: (-)-1-Camphanoyloxyacrylonitrile (=(-)-1-cyanovinyl camphanate; 1) obtained from the commercially available (-)-camphanoyl chloride and 2-oxo-propiononitrile added to furan at 20° in the presence of Cu (BF4)2 · 6H2O or ZnI2 and gave a mixture of 2-cyano-7-oxabicyclo [2.2.1]hept-5-en-2-yl camphanates (2-5) from which isomer 5 could be obtained pure by crystallization. The latter was transformed into (+)-(1R)-7-oxabicyclo[2.2.1]hept-5-en-2-one (6) in high yield and optical purity. Adducts 2-4 were recycled into 1+furan by heating in toluene, and (-)-camphanic acid was recovered after saponification of 5. The absolute configuration of 6 was deduced from its CD spectrum which showed two 1200-cm-1 Franck-Condon series for its n→πCO* transition.

Notizen: The absolute configurations of the two algal pheromones multifidene 1 and viridiene 2 were determined as (+)-(3S, 4S)-3-[(Z)-1-butenyl]-4-vinylcyclopentene and (+)-(3R, 4S)-3-[(1Z)-1, 3-butadienyl]-4-vinylcyclopentene, respectively. The strategy involves enzyme-initiated asymmetric synthesis of the ring-saturated pheromone analogues (+)-8a and (-)-8b and their subsequent catalytic hydrogenation to the chiral cycloalkanes 9a and 9b, only the letter of which is also obtained from the two natural messengers (+)-1 or (+)-2. Biological activity assays proved these enantiomers of 1 or 2 to be the characteristic pheromones for male gametes of the seaweeds Syringoderma, Cutleria multifida and Chorda tomentosa.

Notizen: A method is proposed for correcting experimental fluorescence readings for inner filter effects, i.e. the absorption of the exciting light and/or the absorption of the emitted radiation, which cause the non-linearity between fluorescence intensity and fluorophor concentration. Basically the method consists of measuring the fluorescence intensity at two different points along the diagonal in the cell. Unlike similar methods proposed in the literature, the two points are corrected simultaneously for both absorption of excitation and of emission radiation without the necessity of reading the optical density of the solution, and with a very simple data elaboration.

Notizen: The synthesis of uridine-5′-diphosphate analogs, spin-labeled either at C(4) or C(5) is reported as well as their enzymatic incorporation into ribonucleic acids, some of which had previously been shown to be potent interferon inducers upon annealing with poly (inosinic acid). Also, the synthesis of spin-labeled poly (cytidylic acid) obtained by chemical acylation is presented.

Notizen: Conversion of Bicyclo [3.2.0]hept-2-en-6-one into Cyclopentadienylacetic Acid DerivativesThe reaction of a mixture of 4exo-bromobicyclo [3.2.0]hept-2-en-6-one (2) and -7-one (3) with O- or N-nucleophiles yielded cyclopentadien-5′-yl-acetates 4a-f or-acetamides 4g-h. Due to their rapid isomerization, the products 4 were not isolated, but some of them were demonstrated spectroscopically or captured in situ with maleimide as 10′-substituted norbornene derivatives 7. The formation of 4 from 2/3 involves a fragmentation of the bond between the carbonyl and the bridge-head C-atom, induced by the attacking nucleophile and the leaving Br-ion and aided by the relief of the four-membered ring strain. Some of the isomerization products of 4, i.e. the cyclopentadiene-1′-yl- and 2′-yl-acetyl derivatives were captured with maleimide as the 1′- and 8′-substituted norbornene-derivatives 8 and 9. Two C-nucleophiles did not induce the fragmentation: sodium acetylacetonate substituted the Br-atom and sodium (diethoxyphosphoryl)ethoxycarbonylmethide condensed with the carbonyl group of 2/3, yielding 11/12 and 13/14, respectively.

Notizen: The first total synthesis of racemic neplanocin A (1)After submitting our paper we learned that Arita et al. [J. Am. Chem. Soc.105, 4049(1983)] synthesized the natural enantioner of Neplanocin A. from cyclopentadiene and acylnitroso-3,5-dinitrobenzoic acid is described. The synthesis is suitable for specific isotopic labelling of the hydroxymethyl group of neplanocin A.

Notizen: Urinary metabolites 5-methyl-5-[2-(2,6,6-trimethyl -3-oxo-1-cyclohexen-1-yl)-vinyl]-2-tetrahydrofuranone (1) and 5-[2-(6-hydroxymethyl-2, 6-dimethyl-3-oxo-1- cyclohexen-1-yl)vinyl]-5-methyl-2-tetrahydrofuranone (2) of retinoic acid have been synthesized from 4-[2,2,6-trimethyl-3-(tetrahydro-2 H -pyran-2-yl)oxy-1-cyclohexen-1-yl]-3-buten-2-one (4) and methyl 2-(3,3-ethylenedioxy-1-butenyl)-1, 3-dimethyl-4-oxo-2-cyclohexene-1-carboxylate (5).

Notizen: Synthesis of Optically Active Natural Carotenoids and Structurally Related Compounds. X. Synthesis of (3R,3′S,5′R)-Capsanthin, (3S,5R,3′S,5′R)-Capsorubin, (3′S,5′R)-Cryptocapsin, and Some Related Compounds. A New Approach to Optically Active, Five-Membered-Ring Carotenoid Building Units by HydroboratonThe synthesis of (3R,3′S,5′R)-capsanthin (1), (3S,5R,3′S,5′R)-capsorubin (2), and (3′S,5′R)-cryptocapsin (3), found in the red paprika Capsicum annuum, is described using (+)-camphor (7) as a readily available starting material. As the key reaction, the unsaturated acetal 16 is hydroborated with (+)-diisopinocampheylborane to give the hydroxy ketone 12a in very high chemical and optical yield. A subsequent aldol condensation with 13 in THF/toluene gives 2 in high yield. The C40-compounds 1 and 3 are synthesized using the same type of condensation. The pigments 1-3 are transformed by an Oppenauer oxidation to (3R,5′R)-capsanthone (5), (5R,5′R)-capsorubone (4) and (5′R)-cryptocapsone (6), respectively.

Notizen: The Synthesis of 7-anti-Substituted 2-exo- and 2-endo-NorbornanolsThe title compounds and the corresponding p-toluenesulfonates were prepared in connection with a mechanistic study of C-participation in carbocations.

Notizen: Indolizino [6,5,4,3-aij]quinoline (1) and its 3,9-dimethyl- (2), di-tert-butyl- (3) and diphenyl-(4) derivatives yield persistent radical cations which have been studied by ESR and ENDOR spectroscopy. The corresponding radical anions have also been prepared, but only that of 3 was amenable to a complete characterization by hyperfine data. The π-spin populations in the radical anions are essentially localized on the 13-membered C-perimeter, and thus both the HOMO and LUMO of 1 exhibit an ‘annulenyl character’. The radical anions of 1 and 2 have gradually been converted into those of the corresponding 3,4-dihydro derivatives (1-H2 and 2-H2) which have been unambiguously identified by a combination of preparative and spectroscopic methods.

Notizen: Enantioselective synthesis of phenylalanine was performed by reacting phenylpyruvic acid with pyridoxamine followed by ketimine-aldimine isomerization of the Schiff base formed catalyzed by an optically active copper (II)-complex. By UV and CD measurements it was shown that the enantiomeric excess strongly depends on the reaction conditions and on the reaction time. In favorable cases it reached values up to 80%. The selectivity of the reaction is discussed on the basis of possible structures of the intermediate mixed ligand complex.

Notizen: Ortho Esters with 2,4,10-Trioxaadamantane Structure as Carboxyl Protecting Group; Applications in the Synthesis of Substituted Carboxylic Acids by Means of Grignard ReagentsThe surprising stability of 2,4,10-trioxa-3-adamantyl derivatives 1 against nucleophilic substitution by organomagnesium compounds is discussed and shown to be caused by unfavourable stereoelectronic and steric factors governing the substitution of these cage compounds (Scheme 2). As a consequence, a number of Grignard reagents 2 containing the carboxyl group masked as 2,4,10-trioxa-3-adamantyl group could be prepared and have been reacted in a second step with various electrophiles (cf. Scheme 4). In the products 7-13 and 15b the carboxyl masking group is removed by mild acid hydrolysis and saponification (cf. Scheme 3) to yield the corresponding acids 16a-21a, 22, and 23a. Acids 21a and 23a have been further transformed to give the macrocyclic lactones 24 and 26, isolated from Galbanum oleo-gum-resin, and acid 22 to give 12-methyl-13-tridecanolide (25), isolated from Angelica root oil. In addition 1-bromo-ω-(2,4, 10-trioxa-3-adamantyl)alkanes 1c and 1b have been used to synthesize (±)-methyl recifeiolate (29b) and pure cis-ambrettolic acid ((Z)-32a).

Notizen: Selected [2+2]-cycloadditions of three alkylvinylketenes 2 to one mono- and seven dialkyl-olefins 3 yielded eleven 2-alkyl-2-vinylcyclobutanones 4 (Tables 1 and 2). Three methods were compared, all involving in situ generation of the ketenes 2 by HCl-elimination from α,β-unsaturated acid chlorides 1; the most effective employed a large excess of olefin 3 and a high reaction temperature. The [2+2]-cycloadditions were fully regio- and stereoselective with respect to the olefin 3, but less so with respect to the ketene 2, so that - where possible - two stereoisomers of 4 resulted, namely A and B, whose configurations were determined from their 1H-NMR, spectra, mechanistic considerations and, in one case, 4f, by chemical correlation with a previously known cycloadduct 8.

Notizen: Syntheses and Chemical Properties of New Bridged Quinone Derivatives. Coupling Reactions of Aryldiazonium Salts with 2-Methoxy-1,6-methano[10]annuleneCoupling of 2-methoxy-1,6-methano[10]annulene (3) with the aryldiazonium salts 4a-4i yields the quinone hydrazones 5a-5i. The spectroscopic properties of these products are described. The reaction of 3 with 4-nitrophenyldiazonium tetrafluoroborate buffered with sodium acetate in dry methanol yielded after chromatographic separation the azo derivative 7 on the one hand and a mixture of the valence tautomers 8a and 8b on the other.

Notizen: The influence of remote substituents on the stereochemical outcome of electrocyclization in the silicon-directed Nazarov reaction has been examined. While the degree of stereocontrol was modest (ca. 3:1) the substituent in the major isomer (4,5 or 7-substituted cis-hexahydroind-2-en-1-ones) is always cis to the protons on the ring fusion. Thorough spectroscopic and conformational analysis revealed that divergent senses of electrocyclization are responsible for the observed products. Additional experiments suggest that steric, rather than stereoelectronic forces control the sense of cyclization. A qualitative description of the nature of reactive intermediates in the silicon-directed Nazarov reaction is proposed as well as an explanation for the remarkable efficacy of FeCl3 for inducing the reaction.

Notizen: Differences in the distribution of deuterium at individual atomic sites in vanillin samples are revealed by 2H-NMR measurements, and can be used to determine whether the sample is of natural or synthetic origin.