Library

Notes: Synthesis of (±)-α-ChamigreneCis- and trans-β-ionol (cis and trans-1) underwent acid catalysed dehydration to a mixture of the tetraenes 2-5 in 70-80% yield (Table 1). Irradiation of this mixtures made the 6-(Z), 8-(Z)-isomer 5 accessible (columns 3 and 4 in Table 1). Pyrolysis of the different mixtures at 170° showed, that both isomers, 3 and 5 respectively undergo electrocyclization to dehydrochamigrene (6). The latter was reduced to α-chamigrene (7) by hydrogen on Lindlar catalyst.

Notes: Synthesis of 5,6-Dimethyl-4-oxo-1,3,4,5-tetrahydro-imidazo[4,5-c][1,2,6]thiadiazin 2,2-dioxide and 7-Methyl-4-oxo-1H-3,4-dihydropyrimido[4,5-c][1,2,6]thiadiazin 2,2-dioxideThe derivatives of the above heterocyclic ring systems were prepared by reaction of the corresponding o-amino esters with sulfamoylchloride.

Notes: Studies in Stereochemistry XIV. Diels-Alder adducts in the resin series; action of peracids and acid-catalysed ring opening of epoxidesThe synthesis of Diels-Alder compounds of type 2 with a 17-nor-13(14)-atisène skeleton is described (cf. Schemes 1-3). Depending on the nature and configuration of substituents R1 and R2 on the carbon atoms 15 and 16, an epoxide (24-33) or a ketone (35-38) or a mixture of epoxide, ketone and lactone is obtained by the action of p-nitroperbenzoic acid on the double bond of these adducts (cf. Scheme 4). A simplified reaction scheme is suggested to explain the formation of the various products. In an acid-catalysed reaction, the epoxides isomerize mainly into ketones. Nevertherless, in some cases, dienes (e.g. 52) or hydroxy-γ-lactones of (13R*, 14S*)-configuration (e.g. 50) resulting from the opening of the epoxide ring with retention of configuration were obtained.

Notes: Bridged helicenes: 3,15-ethano- and 3,15-(2-oxapropano)-[7]heliceneThe title compounds (35 and 33, see Scheme 4) have been synthesized from a common intermediate: 3,15-dimethoxycarbonyl-[7]helicene (26). The conformation of the bridged [7]helicenes (X-ray diffraction) and their 1H-NMR. spectra have been compared to the conformation and 1H-NMR. spectra of [7]helicene and 3,15-dimethyl-[7]helicene (10).

Notes: On the structure of Papulacandin B, a new antibiotic with antifungal activityStructure 1 has been established for Papulacandin B (C47H64O17), a new antibiotic from Papularia sphaerosperma (PERS.) HÖhnel by means of spectral analysis of 1 and some derivatives and degradation products. Base catalysed hydrolysis of 1 gave the two unsaturated fatty acids 2 and 3 and the spirocyclic diglycosid 4. The structure of 4 was determined by further degradation reactions.

Notes: Photochemistry of tricyclic β, γ-γ′, δ′-unsaturated ketonesThe easily available tricyclic ketone 1 (cf. Scheme 1) with a homotwistane skeleton yielded upon direct irradiation the cyclobutanone derivative 3 by a 1,3-acyl shift. Further irradiation converted 3 into the tricyclic hydrocarbon 4. However, acetone sensitized irradiation of 1 gave the tetracyclic ketone 5 by an oxa-di-π-methane rearrangement. Again with acetone as a sensitizer the ketone 5 was quantitatively converted to the pentacyclic ketone 6. The conversion 5 → 6 represents a novel photochemical 1,4-acyl shift. The possible mechanisms are discussed (see Scheme 7). The tricyclic ketone 2 underwent similar types of photoreactions as 1 (Scheme 2). Unlike 5 the tetracyclic ketone 9 did not undergo a photochemical 1,4-acyl shift. The epoxides 10 and 14 derived from the ketones 1 and 2, respectively, underwent a 1,3-acyl shift upon irradiation followed by decarbonylation, and the oxa-di-π-methane rearrangement (Schemes 3 and 4). The diketone 18 derived from 1 behaved in the same way (Scheme 5). The tetracyclic diketone 21 cyclized very easily to the internal aldol product 22 under the influence of traces of base (Scheme 5). Upon irradiation the γ, δ-unsaturated ketone 24 underwent only the Norrish type I cleavage to yield the aldehyde 25 (Scheme 6).

Notes: The silver ion-catalysed ring-opening of 2-t-butyl-1-chloro-1-fluoro-2-methyl-cyclopropane (see Scheme 2) gave the expected mixture of primary and tertiary fluoroalkenols, whereas a tricyclic analog (bornane-spiro-chlorofluorocyclopropane) (see Scheme 3) exclusively underwent a Wagner/Meerwein rearrangement upon ionization to lose finally a proton affording a 2-fluoro-1,4-diene.

Notes: Synthesis and reactions of 5,6-dideoxy-6-halogeno-α-D-xylo-hept-5-eno-furanurononitrilesThe 5,6-dideoxy-6-chloro-, 6-iodo- and 6-fluoro-3-O-methyl-α-D-xylo-hept-5-eno-furanurononitriles have been prepared, their properties described as well as the methods used for the assignment of the configuration of the geometrical isomers. Some new reactions of the 6-bromo analog (1) of these compounds are reported. For example, when reacted with 2-mercaptoethanol or N,N′-dimethyl-ethylenediamine in the presence of NaOH, 1 gave the corresponding six-membered ring, stereo-isomers of an oxathiane or of a perhydrodiazine respectively. When the base used was Et3N and the binucleophile the N-methyl-ethanolamine or the N,N′-dimethyl-ethylene-diamine the major product was a cyano-enamine which could be hydrolysed to a β-cyanoketone or cyclized to a five-membered ring, an oxazolidine or an imidazolidine respectively.

Notes: Stereoselective Reductive Dimerisation of α-Cyano-β-(4-pyridyl)acrylic Acid DerivativesCatalytic hydrogenation of the α-substituted β-(4-pyridyl)acrylonitriles 3 and 4 (see Scheme 3) yields via stereoselective reductive dimerization the substituted cyclo-pentene derivatives 7 and 8 (see Scheme 4 and 5) instead of the expected dihydro-products 5 and 6. The mechanism of this reaction is discussed. The structure and relative configuration of 10 have been established by X-ray single crystal analysis.

Notes: HeIα excited photoelectron spectra of pentatetraene and the inferred ionization energies are reported. The first band has a characteristic Franck-Condon envelope similar to the first photoelectron bands of allene and butatriene. The four bands found below 16 eV ionization energy have been assigned to the X̃2E, Ã2E, B̃2E and C̃2B2 states of the radical cation of pentatetraene by comparison with STO-3G and SPINDO calculations on the cumulene series. The correlation scheme includes the 2s shell ionization energies of ethylene, allene and butatriene. The π-orbital ionization trends of the cumulenes are discussed in the framework of localized orbitals calculated with the STO-3G basis set.

Notes: Chemical and Pharmacological Studies on Derivatives of Benzo[de]quinoline, IISpirocompounds of type V (12-18) were synthesized by a carbenium ion cyclization reaction of the intermediates 7 and 11, respectively. 7 was prepared from 2-oxocyclopentanepropionic acid via 1, 2, and 4-6; 11 from the same starting material via 1, 2, and 8-10. - The spiro[7H-benzo[de]quinolin-7,1′-cyclohexan]-2′-one 27 and other compounds of type VI could be synthesized from the (1-isoquinolinyl)ethyl-cyclohexanone 25: 25 is hydroxylated to the hydroxyketone 26; treatment of 26 with a mixture of sulfuric acid and oleum gives 27. The structure of 27 has been proved by transformation into the known spirocyclohexane 33. - Aporphine analogues of type VII (38, 39) were synthesized from the cyclic ketone 34 via either the formylketone 35 and its methyl vinyl ketone adducts 36 and 37 or the methyl ethynyl ketone adduct 40. Compound 40 has also been cyclized to the 10-hydroxy-aporphine 42. 9 compounds of the types mentioned have been screened for hypotensive action in rats, and partly in cats and dogs. Only compound 13 · HCl proved to be (moderately) active in rats and dogs.

Notes: Synthesis of endo- and exo-1,3-dimethyl-2,9-dioxabicyclo[3.3.1]nonaneThe synthesis of a host-specific substance in norway spruce infested by Trypodendron lineatum OLIV. is described (cf. scheme 1 and 2). Alkylation of the acetyl-acetone di-anion (II) with 3-methyl-3-buten-1-yl-bromide (I) followed by sodium boro-hydride reduction yields erythro- and threo-8-methyl-8-nonen-2,4-diol (IV and V) which are separated by chromatography. Their configurations were established by converting them under equilibrium conditions into one (VI) or two (VII and VIII) benzal derivatives. Oxidative cleavage with ozone of the terminal double bond in the erythro diol IV produces a dihydroxy ketone IX which spontaneously cyclizes to endo-1,3-dimethyl-2,9-dioxa-bicyclo[3.3.1]nonane (X). The threo diol V is converted by the same reaction sequence exclusively into exo-1,3-dimethyl-2,9-dioxa-bicyclo-[3.3.1]nonane (XII). Comparison of the NMR. data of the two acetals X and XII with that of the natural product establishes the endo configuration of the latter. A second, more convenient, synthesis of a mixture of the acetals X and XII starting from the bromo-acetal XIII is also reported.

Notes: Exo- and endo-Tricarbonyliron Complexes of Bicyclic 2,3-Dimethylidene Compounds.The preparation of exo- and endo-tricarbonyliron complexes (exo- and endo-5, -6, -8, and 9) of 2,3-dimethylidene-5-bicyclo[2.2.1]heptene(1), -bicyclo[2.2.1]-heptane (2), -5-bicyclo[2.2.2]octene (3) and -bicyclo[2.2.2]octane (4) is described. The complexes are obtained by thermal reaction of the bicyclic butadienes with di-ironenneacarbonyl in hexane solution. exo- and endo-5 are also formed photochemically from ironpentacarbonyl and 1 in pentane solution at -35°. The structural assignment of exo- and endo-5 and -6 is based on their mass-spectra and on coordination shifts in 1H- and 13C-NMR.-spectra exo- and endo-6 are correlated with exo- and endo-5, respectively, by hydrogenation. Hydrogenation of the uncomplexed double bond in exo- and endo-5 occurs in both complexes from the exo side as shown by deuteration experiments. The free ligand 1 reacts in the same stereospecific manner.

Notes: It has been possible to submit the crude hexane extract of the barks of a medicinal plant directly to preparative liquid chromatography. A two step solvent elution gave 6 peaks, four of which readily afforded crystalline material. The entire process required 2-3 hours whereas conventional chromatography required ca. 2 weeks.

Notes: Dysidin, a novel chlorine containing natural product from the sponge Dysidea herbaceaDysidin (1) has been isolated from the marine sponge Dysidea herbacea. It structure has been determined by degradation studies and spectroscopic methods. The synthesis of a degradation product is described. The relative and absolute configuration is established by X-ray diffraction methods.

Notes: Total Synthesis of Betalainescis-4-Oxo-2,6-piperidinedicarboxylic acid dimethyl ester (10) was transformed (44%) into the semicarbazone of 2,3-dihydrobetalamic acid dimethyl ester (13/14) by a modified Horner-Wittig reagent 12. Oxidation of 13/14 afforded 41% of a mixture of stereoisomers of betalamic-acid-dimethyl-ester semicarbazone (4), key intermediate for the synthesis of betalaine pigments. The utility of 4 in this respect was demonstrated on a small scale by its conversion to the dimethyl ester of indicaxanthine (9, 11%) and to the trimethyl ester of betanidine (7, 87%). Hydrolysis of 7 gave betanidine (6).We further describe the synthesis of the trimethyl ester of an oxidized form of betalamic acid (20/21) as well as model condensation reactions on the carbonyl group of cyclohexanone, cis-4-oxo-2,6-diphenylpiperidine (23) and its N-formyl derivative 27.Reaction of 4-oxo-1,2,3,4-tetrahydro-2,6-pyridinedicarboxylic-acid dimethyl ester (40) with acetic anhydride or with triethyloxonium tetrafluoroborate resulted in O-acylation or in O-alkylation along with dehydrogenative aromatization to yield the derivatives 39 or 42, respectively, of chelidamic acid.

Notes: Metal Complexes of N-substituted 3-Imino-isoindolinonesThe condensation of 3-imino-isoindolinone 4 and benzimidazoles or benzthiazoles containing activated methyl-, methylen- or aminogroups (5 resp. 6), yields the iso-indolinone-ligands 1 and 2. Metal ions such as Co2+, Ni2+, Cu2+ and Zn2+ form (1:2)-complexes with these ligands of very high chemical and photochemical stabilities. The magnetic properties of these complexes indicate that the geometry around the central atoms is distorted tetrahedral. A X-ray diffraction study of one of the Co(II)-complexes confirms these findings.

Notes: Austauschversuche mit radioaktivem Nickel zeigen, dass Ni2+ und Pd2+ in Mercaptoäthylamin(MEA-)-Komplexen austauschbar sind. Aus UV./VIS.- und 1H-NMR.-spektroskopischen Daten geht hervor, dass die Anordnung der Metallionen in Ni2Pd(MEA)4Cl2 symmetrisch ist (Ni Pd Ni), in NiPd2(MEA)4Cl2 dagegen asymmetrisch (Ni Pd Pd).

Notes: ESR. spectra of the chlorine substituted phenoxy radicals listed in Table 1, which were produced by photo-oxidation of the parent phenols in aprotic solvents, are reported. In most cases the chlorine splittings could be resolved and analysed in detail. Experimental data as well as quantum chemical calculations were used for assignment of all measured chlorine couplings and determination of their relative signs.Spin density distributions and polarization parameters for chlorine are discussed and compared with the results from current semiempirical molecular orbital theories.Chlorine couplings, associated with the larger splittings are found positive in sign, whereas signs of small couplings appear difficult to establish. Limitations in the applicability of McConnell or Karplus-Fraenkel type relations to chlorine substituted aromatic radicals will be discussed and related to peculiar properties of the spin density matrix of such systems.

Notes: On the regioselectivity of cycloaddition reactions of photochemically generated benzonitrile-isopropylidesThis paper deals with the physical and chemical differences of zwitterionic benzo-nitrile-isopropylides, which differ by a p-substituent in the phenyl ring (H, F, OCH3; Scheme 2). These dipolar species (4-6) are produced by irradiation of the corresponding 2 H-azirines (1-3; Scheme 1) in a 2-methylpentane glass at -185°. Their UV. spectra are reproduced in the Figure. The spectra of 4 and 5 are characterized by an ‘aromatic band’ at short wavelength, and a longer wavelength band at approximately 275 nm, which is considered to be characteristic of the nitrile-ylide system. The UV. spectrum of the methoxy derivative 6, which shows a broad absorption at 260 nm, arises by an addition of the ‘nitrile-ylide band’ and the anisole band. The three dipolar species 4-6 do not show any significant differences in the regioselectivity of the cycloaddition with methyl α-methacrylate even though F and OCH3 have quite different σ-constants (Scheme 1). The addition according to modus A is very much preferred (B/A = 0,076). - It seems, that the substituents F and OCH3 do not affect the physical and chemical behaviour of the parent benzonitrile-isopropylide (4). All three dipolar species 4-6 react regiospecifically according to modus A with methyl trifluoroacetate (Scheme 1). The regioselectivity is reduced in the cycloaddition of 4 with methyl propiolate and ethyl phenylpropiolate (B/A = 0,04 and 0,28, respectively). The reduced regioselectivity in the latter case may be attributed to a reduced polarity of the triple bond in the dipolarophile.

Notes: Structure of Cantharidine, C10H12O4An X-ray structure determination of the title compound confirms the correctness of the molecular stereochemistry as deduced earlier from chemical considerations.

Notes: Model Calculations on Hexacyano- and Pentacyanoferrate Complexes with Aromatic Nitrogen HeterocyclesUsing the extended Hückel method, theoretically predicted chemical, photochemical and spectroscopic properties of these complexes are compared with experimental data. A better understanding of the photochemistry is attempted by analysis of the low energy CT absorption. Starting from the amminopentacyanoferrate the spectroscopic properties of the pentacyanoferrate complexes with aromatic heterocycles are described by adding the ‘d-π*’ MLCT and the π-π* transitions. The results obtained on the mononuclear pyrazine compounds suggest a very simple way to understand the binuclear pyrazine complexes. Some properties of the hexacyanoferrates can be better explained if all valence orbitals of the ligands are considered. In all examples the influence of the ‘π-backbonding’ is discussed.

Notes: The Photochemistry of Conjugated Epoxy-Inones: Photolysis of 5,6-Epoxy-5-isopropyl-6-methyl-hept-3-in-2-onThis paper continues the series of investigations of the photochemistry of α,β-unsaturated γ,δ-epoxyketones by examining the hitherto unknown photochemical behaviour of α,β-acetylenic-γ,δ-epoxy-ketones. As model compound, the aliphatic epoxy-ynone 7 (thermally stable at 180°) was synthesized (Scheme 1). It can be converted with BF3O (C2H5)2 in good yields to the 1,5-diketone 8, the yne-1,4-diketone 49 and in small amounts to the fluorhydrine 50 (Scheme 1).On n,π*- or π, π*-excitation, 7 shows mainly cleavage of the C (γ)-O-bond to give a diradical a (Scheme 11), whose ultimate fate is strongly solvent dependent. In acetonitrile a mainly rearranges to the 1,5-diketone 8 and, to a smaller extent, shows fragmentation to acetone and formation of polymers. Except for small amounts of the dimeric products 9A,9B and biphenyl, the same compounds are obtained in benzene. In cyclopentane, however, a gives only little of 8, and mainly a plethora of compounds formed by a radical process like H-abstraction from solvent, incorporation of cyclopentylradicals, dimerization and fragmentation reactions (9A, 9B, 11-20) (Scheme 3). Irradiation of 7 in propan-2-ol or in dioxane yields products of analogous radical processes as well of photoreduction (Scheme 4). However, the analogous epoxyenone 32 gives mainly products of photoisomerizations without interference by the solvent [6].On photochemical excitation in acetonitrile, the 1,5-diketone 8 shows unspecific decomposition, but in cyclopentane it yields the reduction products 12, 26A, 26B, 27, 28 plus cyclopentylcyclopentane (15) (Scheme 6).

Notes: The chemical resolution of γ,γ′-di-t-butyl DL-N-benzyloxycarbonyl-γ-carboxy-glutamate is described in detail (preliminary account see [1]). The D (-)-derivative was obtained as a crystalline quinine salt, and the L (+)-derivative as a crystalline salt with (-)-ephedrine in yields of 44 and 70%, respectively. Physical data are indicated for the enantiomers of γ,γ′-di-t-butyl N-benzyloxycarbonyl-γ-carboxyglutamate, γ,γ′-di-t-butyl γ-carboxyglutamate, and γ-carboxyglutamic acid. The absolute configurations and optical purities of the γ,γ′-di-t-butyl (+)- and (-)-N-benzyloxycarbonyl-γ-carboxyglutamates were determined by removal of the protecting groups and decarboxylation to optically active glutamic acid.

Notes: The purpose of this communication is to describe the preparation and some properties of the first two synthetic peptides containing D- and L-γ-carboxyglutamic acid. Use was made of N-protected γ,γ′-di-t-butyl-γ-carboxyglutamic acids (D, L, and DL) described earlier [1 a]. Preliminary 1H-NMR. data (360 MHz) indicate a restricted rotation of the Gla side chain in the free amino acid as well as in the C-terminal Gla of Gla-Gla in H2O solution at acid pH. The proton dissociation from Gla and Gla-Gla was studied by potentiometric titration and NMR. methods. The pH titration in the presence of Ca2+ ions shows that Gla-Gla has a much higher association constant for this cation than Gla. It is almost as great as that of prothrombin (pCa2+ = 3.2 vs. 3.5).

Notes: Photochemical Cyclization of o-, m-, p-Allylanisoles and o-AllylanilinesThe compounds irradiated are summarized in Scheme 1. 2-Allylaniline and N-Alkyl Derivatives. Irradiation (ca. 3 h) of compounds 1-3 with a high pressure mercury lamp in benzene solution under argon (quartz vessel) gave in 40-80% yield the corresponding 2-methylindolines 20, 22 and 25, respectively (Scheme 3). Tetrahydroquinolines (23, 26) were formed only in minor amounts (0,5%). Irradiation in methanol solution yielded in addition to the indolines the 2-(2′-methoxypropyl)-anilines 21,24 and 27, respectively, in a ratio of ca. 0.3, 1.5 and 1.0 with respect to the indolines (Scheme 3). Similar results were obtained in ethanol solution. The observation that the photoreactions in benzene or methanol are not quenched by (E)-piperylene or sensitized by acetone suggests that the transformation starts from the singlet manifold of the aniline chromophor. As outlined in Scheme 11 it is proposed that the excited molecules undergo an intramolecular electron transfer to give an acceptor(olefinic side chain)/donor(aniline part) complex (EDA complex; see [28]) of type {a,b} in which the positive charge is mainly located at the nitrogen atom and the negative charge at C(3′) of the allyl substituent. That the negative charge resides predominantly at C (3′) - independently of alkyl substitution at C (3′) (see experiments cited in [26]) - may be due to electrostatic attraction of the charges. Thus, the following H-transfer occurs almost regiospecifically to give the singlet diradical c which cyclizes directly or via the spirocyclopropane derivative d to the indoline derivative 22. Intermediate d is also responsible for the formation of the 2′-methoxypropyl compounds: It is suggested that in the polar solvent methanol d is partially converted to the zwitterion e, the immediate precursor of 24. Experiments with the deuteriated reactants N-d-2 and 2′-d1-2 (Scheme 3) are in agreement with the proposed mechanism.N, N-Dialkyl-2-allylanilines and Allylanisoles. Upon irradiation in methanol or benzene, these aniline derivatives undergo cyclization to give as the only products the corresponding 2-cyclopropylanilines in 50-70% yield (Scheme 4). 2-, 3- and 4- allylated anisoles behave in the same way on irradiation (Schemes 6-8) as long as the allyl group carries no substituent (CH3, Cl) at the double bond (Schemes 9, 10). No photolytic cyclopropane ring formation is observed with the naphthalene derivatives 7, 8, 17 or 18 (Scheme 1). Experiments with the deuteriated compounds 2′-d1-4 and 1′, 1′-d2-11 - synthesized according to Scheme 2 - indicate that in all cases the cyclopropane formation occurs with concomitant 1,2 aryl migration (Schemes 5, 6) which characterizes the reaction as an aromatic di-π-methane rearrangement (Scheme 14). In contrast to the photoreactions described above the cyclopropane ring formation can be sensitized by acetone or quenched totally by (E)-piperylene. A comparison of the triplet energies (ET) of the aromatic and olefinic chromophor of the reactants (cf. Table 4) shows that the di-π-methane rearrangement is only effective when ET of the aryl part is lower than that of the olefinic part, but not by more than 20 kcal/mol. In substrates carrying substituents at the olefinic double bond the energy of T1 of the allyl group drops beneath that of the aryl part. In these cases no di-π-methane rearrangement is observed because an effective deactivation of T1 of the aryl part occurs by (E)/(Z) isomerization of the side chain as is demonstrated by the photochemical behaviour of compound 10 (Scheme 10). This concept seems to be of general significance for related di-π-methane rearrangements in cyclic systems (cf. Scheme 16; further examples: Scheme 15).

Notes: On the incorporation of geraniol and farnesol into cantharidinEarlier investigations [1] have shown that cantharidin (1) is biosynthesized by the male Lytta vesicatoria L. (Meloidae, Coleoptera) from the common terpenoid precursors mevalonate and farnesol (3). To prove if geraniol (2) is incorporated via farnesol (3) into cantharidin (1) the following geraniols have been synthesized and injected into either larvae or male adult Lytta vesicatoria, partly in a mixture with synthetic 11′, 12-[3H]-farnesol as an internal standard: 2-[14C]-, 7-[14C]-, 7′, 8-[14C]-, 7′, 8-[3H]-geraniol. Unexpectedly, geraniol (2) was not specifically incorporated into cantharidin (1) perhaps due to its higher toxicity or its faster degradation relative to the other precursors before incorporation. The incorporation of U-[14C]-leucine, U-[14C]-isoleucine and 1-[14C]-glucose into cantharidin (1) via their metabolites is evident by degradation studies, whereas 1-[14C]- and 2-[14C]-glycine do not serve as precursors for cantharidin (1).

Notes: Bildung von 5-Hydroxy-indan-2-on bei Hydrolyseversuchen mit 9-Äthylendioxy-bicyclo[3.3.1]nonan-3,7-dionVerschiedene Versuche, 9-Äthylendioxy-bicyclo[3.3.1]nonan-3,7-dion (2) durch Hydrolyse in das entsprechende Triketon 3 umzuwandeln, führten nur zu 5-Hydroxy-indan-2-on (4) und in einem Fall auch noch zu etwas 7,9-Bis(äthylendioxy)-bicyclo-[3.3.1]nonan-3-on (5). Unter milderen Hydrolysebedingungen reagierte 2 gar nicht.Die Bildung von 4 aus 2 wird über eine Wagner-Meerwein-Umlagerung und nach-folgende Eliminierung von Äthylenglycol formuliert. Das so entstandene Äthylenglycol reagiert mit noch vorhandenem Acetal 2 zum Bis-acetal 5, was als weitere Bestätigung der Resistenz von 2 gegen Hydrolyse gelten darf.

Notes: Starting from ethyl 2-cyclohexen-1-carboxylate (3) the total synthesis of the perhydrohistrionicotoxin intermediate 23 was achieved in 25% overall-yield. The two key steps involve a positionally specific addition of HOBr to the oxime-olefin 7 and the alkylation of bromooxime 17 with 1-lithio-1-butyne. The latter represents a novel method for stereospecific and position-specific introduction of a nucleophilic butyl equivalent in α-position to a ketonic carbonyl group.

Notes: Experiments on the competitive incorporation of farnesol-stereoisomers into cantharidinFarnesol (2) has been demonstrated to be an efficient precursor for cantharidin (1), into which it is transformed by elimination of C(1), C(5), C(6), C(7) and C(7′) [1]. The following incorporation experiments with doubly labelled (3H and 14C) stereoisomers of farnesol present strong evidence that (E,E)- farnesol ((E,E)-2) in fact is the precursor for cantharidin, whereas (2E, 6Z)-2 and (Z,Z)-2 are not utilized for the biosynthesis of cantharidin. A possible mechanism for the incorporation of (2Z,6E)-farnesol ((2Z,6E)-2) to an extent of 56,8% relative to (E,E)-2 is discussed.

Notes: Synthesis of benzofulvenes and dibenzofulvenes via 1-chloroalkyl-acetates1,2-Benzofulvene (6a) and 1,2,3,4-dibenzofulvene (7a) as well as the corresponding 6-methyl- and 6-phenyl-derivatives are prepared by reaction of sodium indenide and sodium fluorenide with 1-chloroalkyl acetates (3), followed by elimination with KOC(CH3)3. The over-all yields are comparable with the results of the fulvene series and are in most cases considerably higher than the yields of the Thiele-method.

Notes: Thermal and photochemically induced intramolecular 1,3-dipolar cycloaddition reactions of 4-phenyl-3-(2-allylphenyl)-sydnoneThe title compound 9 was synthesised in the usual way, starting from 2-allylaniline and ethyl 2-bromo-2-phenylacetate, via the nitrosaminacid 8 (Scheme 2). 9 reacts at room temperature with its potential azomethinimine-function in an intramolecular [3+2]-cycloaddition to give the tricyclic compound 11 (Scheme 2). On irradiation, 9 yields the dihydro-3H-pyrazolo[2,3-a]indole 10 which probably arises by intramolecular [3+2]-cycloaddition of the corresponding intermediate nitrilimine.

Notes: 2-Cyclopentenyl and 3-phenyl-2-cyclopentenyl methyl ketones (15-18, 30, 31) undergo a 1,3-acetyl shift on direct irradiation, and the oxa-di-π-methane rearrangement to photochemically non-interconverting endo and exo bicyclo-[2.1.0]pentyl methyl ketones on triplet sensitization. Exceptions include the 2-methyl-3-phenyl-2-cyclopentenyl methyl ketone 32 and the 1-phenyl-2-cyclo-pentenyl methyl ketone 44 which are unreactive on direct irradiation and on triplet sensitization, respectively, and the 2-phenyl-2-cyclopentenyl methyl ketones 42 and 43 which do not react under either condition. The reactive triplet of the 3-phenyl-2-cyclopentenyl methyl ketone 30 has been identified as the localized styrene π,π*-state of ET=59 kcal/mol by comparison of its phosphorescence at 77K in rigid glasses with that of 1-phenyl-cyclopentene, and by the independence of the quantum yield on sensitizer energy in the range of 61-74 kcal/mol.

Notes: In recent years the volume of activation Δ V* has become a powerful tool in chemical kinetics. High resolution NMR. spectroscopy is now one of the most common techniques used in the study of the kinetics of labile chemical systems. In order to measure Δ V* by this technique, we have built a 1H-probe-head, for a Fourier transform spectrometer, working up to 4 kbar and with a resolution of 0.6 Hz. The temperature is regulated and measured with an accuracy better than 0.2°. The high pressure probe-head has been tested on a chemical system showing a dissociative-associative crossover for the ligand substitution mechanism. It had been shown previously that the ligand exchange TaBr5 · L + *L ⇄ TaBr5 · *L + L proceeds via a D mechanism when L=Me2O, and via an Ia mechanism when L=Me2S. As expected, ΔV0* is positive (+30.5 ± 2.0 cm3 mol-1) for the dissociative process and negative (-12.6 ± 1.0 cm3 mol-1) for the associative one.

Notes: Investigations on Aromatic Amino-Claisen RearrangementsThe thermal and acid catalysed rearrangement of p-substituted N-(1′,1′-dimethylallyl)anilines (p-substituent=H (5), CH3 (6), iso-C3H7 (7), Cl (8), OCH3 (9), CN (10)), of N-(1′,1′-dimethylallyl)-2,6-dimethylaniline (11), of o-substituted N-(1′-methylallyl)anilines (o-substituent=H (12), CH3 (13), t-C4H9 (14), of (E)- and (Z)-N-(2′-butenyl)aniline ((E)- and (Z)-16), of N-(3′-methyl-2′-butenylaniline (17) and of N-allyl-(1) and N-allyl-N-methylaniline (15) was investigated (cf. Scheme 3). The thermal transformations were normally conducted in 3-methyl-2-butanol (MBO), the acid catalysed rearrangements in 2N-0,1N sulfuric acid. - Thermal rearrangements. The N-(1′,1′-dimethylallyl)anilines rearrange in MBO at 200-260° with the exception of the p-cyano compound 10 in a clean reaction to give the corresponding 2-(3′-methyl-2′-butenyl)anilines 22-26 (Table 2 and 3). The amount of splitting into the anilines is 〈4% (10 gives ≃ 40% splitting). The secondary kinetic deuterium isotope effect (SKIDI) of the rearrangement of 5 and its 2′,3′,3′-d3-isomer 5 amounts to 0.89±0.09 at 260° (Table 4). This indicates that the partial formation of the new s̰-bond C(2), C(3′) occurs already in the transition state, as is known from other established [3,3]-sigmatropic rearrangements. The rearrangement of the N-(1′-methylallyl)anilines 12-14 in MBO takes place at 290-310° to give (E)/(Z)-mixtures of the corresponding 2-(2′-Butenyl)anilines ((E)- and (Z)-30,-31, and -32) besides the parent anilines (5-23%). Since a dependence is observed between the (E)/(Z)-ratio and the bulkiness of the o-substituent (H: (E)-30/(Z)-30=4,9; t-C4H9: (E)-32/(Z)-32=35.5; cf. Table 6), it can be concluded, that the thermal amino-Claisen rearrangement occurs preferentially via a chair-like transition state (Scheme 22). Methyl substitution at C(3′) in the allyl chain hinders the thermal amino-Claisen-rearrangement almost completely, since heating of (E)-and (Z)-16, in MBO at 335° leads to the formation of the expected 2-(1′-methyl-allyl) aniline (33) to an extent of only 12 and 5%, respectively (Scheme 9). The main reaction (≃60%) represents the splitting into aniline. This is the only observable reaction in the case of 17. The inversion of the allyl chain in 16 - (E)- and (Z)-30 cannot be detected - indicated that 33 is also formed in a [3, 3]-sigmatropic process. This is also true for the thermal transformation of N-allyl-(1) and N-allyl-N-methylaniline (15) into 2 and 34, respectively, since the thermal rearrangement of 2′, 3′, 3′-d3-1 yields 1′, 1′, 2′-d3-2 exclusively (Table 8). These reaction are accompanied to an appreciable extent by homolysis of the N, C (1′) bond: compound 1 yields up to 40% of aniline and 15 even 60% of N-methylaniline ((Scheme 10 and 11). The activation parameters were determined for the thermal rearrangements of 1, 5, 12 and 15 in MBO (Table 22). All rearrangements show little solvent dependence (Table 5, 7 and 9). The observed ΔH≠ values are in the range of 34-40 kcal/mol and the ΔS≠ values very between -13 to -19 e.u. These values are only compatible with a cyclic six-membered transition state of little polarity. - Acid catalysed rearrangements. - The rearrangement of the N-(1′, 1′-dimethylallyl) anilines 5-10 occurs in 2N sulfuric acid already at 50-70° to give te 2-(3′-methyl-2′-butenyl)anilines 22-27 accompanied by their hydrated forms, i.e. the 2-(3′-hydroxy-3′-methylbutyl) anilines 35-40 (Tables 10 and 11). The latter are no more present when the rearrangement is conducted in 0.1 N sulfuric acid, whilst the rate of rearrangement is practically the same as in 2 N sulfuric acid (Table 12). The acid catalysed rearrangements take place with almost no splitting. The SKIDI of the rearrangement of 5 and 2′, 3′, 3′-d3-5 is 0.84±0.08 (2 N H2SO4, 67, 5°, cf. Table 13) and thus in accordance with a [3,3]-sigmatropic process which occurs in the corresponding anilinium ions. Consequently, the rearrangement of a 1:1 mixture of 2′, 3′, 3′-d3-5 and 3, 5-d2-5 in 2 N sulfuric acid at 67, 5° occurs without the formation of cross-products (Scheme 13). In the acid catalysed rearrangement of the N-1′-methylallyl) anilines 12-14 at 105-125° in 2 N sulfuric acid the corresponding (E)- and (Z)-anilines are the only products formed (Table 14 and 15). Again no splitting is observed. Furthermore, a dependence of the observed (E)/(Z) ratio and the bulkiness of the o-substituent (H: (E)/(Z)-30 = 6.5; t-C4H9: (E)-32/(Z)-32 = 90; cf. Table 15) indicates that also in the ammonium-Claisen rearrangement a chair-like transition state is preferentially adopted. In contrast to the thermal rearrangement the acid catalysed transformation in 2 N-O, 1 N sulfuric acid (150-170°) of (E)- and (Z)-16 as well as of 1 and 15, occurs very cleanly to yield the corresponding 2-allylated anilines 33, 2 and 34 (Scheme 15 and 18). The amounts of the anilines formed by splitting are 〈2%. During longer reaction periods hydration of the allyl chain of the products occurs, and in the case of the rearrangement of (E)- and )Z)-16 the indoline 45 is formed (Scheme 15 and 18). All transformations occur with inversion of the allyl chain. This holds also for the rearrangement of 1, since 3′, 3′-d2-1 gives only 1′, 1′-d2-2 (Scheme 17). The activation parameters were determined for the acid catalysed rearrangement of 1, 5, 12 and 15 in 2 N sulfuric acid (Table 22). The ΔH≠ values of 27-30 kcal-mol and the ΔS≠ values of +9 to -12 e.u. are in agreement with a [3, 3]-sigmatropic process in the corresponding anilinium ions. The acceleration factors (kH+/kΔ) calculated from the activation parameters of the acid catalysed and thermal rearrangements of the anilines are in the order of 105 - 107. They demonstrate that the essential driving force of the ammonium-Claisen rearrangement is the ‘delocalisation of the positive charge’ in the transition state of these rearrangements (cf. Table 23). Solvation effects in the anilinium ions, which can be influenced sterically, also seem to play a role. This is impressively demonstrated by N-(1′, 1′-dimethylallyl)-2, 6-dimethylaniline (11): its rearrangement into 4-(1′, 1′-dimethylallyl)-2, 6-dimethylaniline (43) cannot be achieved thermally, but occurs readily at 30° in 2 N sulfuric acid.From a preparative standpoint the acid catalysed rearrangement in 2 N-0, 1 N sulfuric acid of N-allylanilines into 2-allylanilines, or if the o-positions are occupied into 4-allylanilines, is without doubt a useful synthetic method (cf. also [17]).

Notes: Investigation of the complexing of Na+, K+, Ca2+ and Ba2+ with some uncharged ligands by 13C-chemical shift and spin-lattice relaxation time measurementsThe influence of Na+, K+, Ca2+ and Ba2+ ions on 13C chemical shifts and on spin-lattice relaxation times of some electrically neutral ion carriers was investigated. In the solvents CD3CN and CD3OD and in presence of an excess of metal ions ligand 4 (see the Scheme) forms complexes of 1:1 stoichiometry. All four oxygen atoms of the ligand as well as solvent molecules take part in the coordination. In CDCl3 as solvent, for all ions investigated except sodium, only 1:2 complexes (metal/ligand) were observed with 4. Sodium ions form both 1:1 and 1:2 complexes in this solvent. In the 1:2 complexes of the investigated monovalent ions only one, in those of the divalent ions both amide carbonyl groups of ligand 4 take part in the coordination.

Notes: The structure and absolute configuration of a new acetylenic alkaloid gephyrotoxin isolated from skin extracts of the Colombian frog Dendrobates histrionicus, has been determined by Röntgen-ray crystallography. Gephyrotoxin, previously referred to as HTX-D, is a novel tricyclic alkaloid, [1 S, 3aS, 5aS, 6S(Z), 9a R, 10 R]dodeca-hydro-6-(2-penten-4-yl)pyrrolo[1,2-a]quinoline-1-ethanol. Dihydrogephyrotoxin, a minor skin constituent, contains a 6-(2,4-pentadienyl)substituent. Two further spiropiperidine alkaloids related in structure to histrionicotoxin, (6 R[6α[2S*(Z)],[7β(Z), 8α]]7-(1-buten-3-ynyl)-2-(2-penten-4-ynyl)-1-azaspiro [5.5]undecan-8-ol), have been isolated from Dendrobates histrionicus: allodihydrohistrionicotoxin which differs from histrionicotoxin in having a 2-(4-pentynyl)-substituent, while allotetrahydrohistrio-nicotoxin, a minor constituent, has 2-(4-pentynyl)- and 7-(1,3-butadienyl)-substituents. Three alkaloids related in structure to pumiliotoxin C, ([2 S, 4a S, 5R, 8a R]5-methyl-2-n-propyl-cis-decahydroquinoline), have been isolated from Dendrobates histrionicus. These alkaloids, with molecular weights of 195, 223, and 269, have, respectively, a 2-butylsubstituent, 2-propyl and 5-propyl-substituents, and 2-(3,4-pentadienyl) and 5-(2-penten-4-ynyl)-substituents. The last compound was hydrogenated to a dodecahydro-derivative identical in molecular weight, but not in other properties, with authentic dodecahydro-8-deoxy-histrionicotoxin, which was prepared from histrionicotoxin. Gephyrotoxin, in contrast to histrionicotoxin and pumiliotoxin C, is a muscarinic antagonist.

Notes: New results concerning the mechanism of retentive substitution at the three membered ring of propellanesThe reaction of the endo- and exo-bromide 1a and 1b with acetate ion in aprotic polar solvents carried out at high concentrations of 1 furnishes the dimeric dehydro-halogenation products 3a and 3b, the structures of which are determined by x-ray crystallography (Fig. 1). The formation of 3a and 3b as well as of the products 2 of a retentive substitution process can be explained by assuming that the strained benzo-tropones 4 are intermediates. Their high barrier to inversion is confirmed by π-SCF-molecular mechanics calculations.

Notes: (Z)-5-Tetradecen-14-olide (1), (Z)-5-dodecenyl acetate (2), and (Z)-5-tetradecenyl acetate (3) have been isolated from the absolute oil of Hibiscus abelmoschus L. The lactone 1 is a new macrocyclic musk compound, and the occurrence of the two acetates 2 and 3 in a plant is reported for the first time. Syntheses of the three compounds are described.

Notes: Synthesis of four chiral electrophilic C3- and C4-synthons from hydroxycarboxylic acidsThe chiral alkylating reagents 4, 6c, and 10a/b are prepared from lactic, β-hydroxy butyric, and malic acid, respectively. Their use in natural product synthesis is referred too.

Notes: The four isomeric 5, 10-pentadecadienals 1, 2, 3 and 4 were prepared by stereo-selective routes from acetylenic precursors. Two of them, 2 and 4, were also made by Wittig reaction from 2-hydroxytetrahydropyran (29). 2-Hydroxytetrahydropyran (29) yields (Z)-5-alkenols efficiently by Wittig reaction, and (Z)-4-hexenol was similarly made from 2-hydroxytetrahydrofuran (66).

Notes: A short approach to the tricyclo [5.3.1.03,8] undecane derivatives 1, 10, 11 and 12 and to the tricyclo [4.3.1.03,7] decane derivative 2, starting from industrially available intermediates, is described. Of the compounds 1, 10, 11, and 12, which possess the ring system of patchouli alcohol, 12 also exhibits a woody, patchouli-like note. The 1H-NMR.-spectra of 1, 2 and 8-12 are discussed.

Notes: Nucleosides and Nucleotides. Part 10. Synthesis of Thymidylyl-(3′-5′)-thymidylyl-(3′-5′)-1-(2′-deoxy-β-D- ribofuranosyl)-2(1 H)-pyridoneThe synthesis of 5′-O-monomethoxytritylthymidylyl-(3′-5′)-thymidylyl-(3′-5′)-1-(2′-deoxy-β-D-ribofuranosyl)-2(1H)-pyridone ((MeOTr)TdpTdp∏d, 5) and of thymidylyl-(3′-5′)-thymidylyl-(3′-5′)-1-(2′-deoxy-β-D-ribofuranosyl)-2(1 H)-pyridone (TdpTdp∏d, 11) by condensing (MeOTr) TdpTd (3) and p∏d(Ac) (4) in the presence of DCC in abs. pyridine is described. Condensation of (MeOTr) TdpTdp (6) with Πd(Ac) (7) did not yield the desired product 5 because compound 6 formed the 3′-pyrophosphate. The removal of the acetyl- and p-methoxytrityl protecting group was effected by treatment with conc. ammonia solution at room temperature, and acetic acid/pyridine 7 : 3 at 100°, respectively. Enzymatic degradation of the trinucleoside diphosphate 11 with phosphodiesterase I and II yielded Td, pTd and p∏d, Tdp and Πd, respectively, in correct ratios.

Notes: One unsaturated and three branched long-chain primary alcohols have been converted into N-alkyl-2-pyrrolidones for investigation by mass spectrometry. The EI. mass spectra of these derivatives have been found to exhibit unambiguously the branching points and, albeit less clearly, the position of a double bond in the chain.

Notes: 1H-NMR., 13C-NMR., UV. and CD. spectral data of synthetic (3S, 3′S)-astaxanthin, its 15-cis isomer, and some related compounds1H-NMR., 13C-NMR., UV. and CD. spectra are reported for synthetic (3S, 3′S)-astaxanthin (1), its 15-cis isomer (2), its diacetate (3), and the 15, 15′-didehydro compound (5). These data prove the identity of the synthetic and the naturally occuring compound 1. A full interpretation of the 1H- and 13C-NMR. spectra is given and confirms the configuration of all the double bonds. The conformation of the cyclohexene end group of all the compounds is shown to be identical. The signs of the different CD. maxima of 15-cis-astaxanthin are found to be opposite to those of the all-trans compound.

Notes: Phytochemistry of genus Gentiana, XX. Identification of new di-O-glucosides of C-glucosylflavones in Gentiana asclepiadea L.Two new O-glucosides of C-glucoside flavonic compounds [isoorientin-2″,4′-di-O-β-D-glucoside (1) and isovitexin-2″-4′-O-β-D-glucoside (2)] have been isolated from leaves of Gentiana asclepiadea L. This is the first case of di-O-glucosides of C-glucoside flavones occurring in nature.

Notes: On the Mechanism of the Cope RearrangementThe rates of the Cope rearrangement of 2,5-dicyano-3-methyl-hexa-1, 5-diene (12), (E)- and (Z)-2, 5-dicyano-hepta-1,5-diene ((E)- and (Z)-14) as well as of 2, 5-dimethoxycarbonyl-3-methyl-hexa-1,5-diene (13) and (E)- and (Z)-2,5-dimethoxycarbonyl-hepta-1,5-diene ((E)- and (Z)-15) were measured in decane solution in the temperature range of 50 to 150° (see Tables 5 and 8 to 12). A detailed English summary of this work is given in [1 b].

Notes: The irradiation of 17 β-hydroxy-2-oxa-androst-4-en-3-one (1) yield a cyclopropane derivative 2, which is the result of a rearrangement, formally analogous to the ‘type A rearrangement’ of the enones. Two other products, the dihydroxy compound 5 and the dimer 6, have also been isolated (Scheme 1).

Notes: Ircinianin (2), a new furano-sesterterpenetertronic acid, has been isolated from a marine sponge of the genus Ircinia. Structure 2 has been established by X-ray diffraction methods.

Notes: Repeatable ring expansions by [2,3]-sigmatropic shifts in cyclic allylsulfonium allylides; synthesis of medium- and large-sized thiacyclesAllylation of a 2-vinyl thiacyclus with allyl bromide in 2,2,2-trifluoroethanol followed by ylide generation by use of aqueous potassium hydroxide results in a [2,3]-sigmatropic rearrangement with formation of a new 2-vinyl thiacyclus enlarged by three carbon atoms (Scheme 1). In this way, starting from the 5-membered ring 1, a series of four ring enlargement sequences leads to the 17-membered thiacycles 9 and 10 via the 8-, 11- and 14-membered rings 4, 7 and 8 (Scheme 2).

Notes: 31P-NMR. spectra for a series of phosphite complexes of platinum (0) have been measured. Low temperature studies have revealed the existence in solution of the mixed complexes Pt[PPh3]2[P(OPh3)3]2 and Pt[PPh3][P(OPh)3]3 of which the former is isolable.

Notes: Note on some complexes between nikethamide and/or pemoline with various salts, especially calcium aminoalkylphosphatesA number of binary and ternary complexes of nikethamide and/or pemoline with various calcium salts, particularly calcium aminoalkylphosphates, have been prepared in order to assess their pharmacological properties. The formation of such complexes has been established by IR. spectroscopy.

Notes: Syntheses and caracterization of bifunctional germylenesSeveral synthetic methods of bifunctional germylenes GeY2 (Y = RO, PhO, RS, CH3COO, Acac; Y2 = OCH2CH2O, SCH2CH2S) or GeXY (Y = RO, X = Cl; Y = RS, X = Cl; Y = Acac, X = Cl) such as exchange reactions, dechlorhydratation reactions and nucleophilic substitutions from GeCl2 · dioxane are described.Some more synthesis of divalent species GeY2 from Ge(OR)2 by transalcoxylation and from Ge(Cp)2 by cleavage using protic species will be presented.The stability and reactivity of these germylenes are discussed. Difunctionnal germylenes give generally a selfpolycondensation reactions. However, their reactivity in situ shows a effective participation of monomeric species GeY2.

Notes: Fluorotricyanomethane is prepared from potassium tricyanomethanide and perchlorylfluoride. The crystal structure of this compound (orthorhombic, space group P212121, with a=6.270, b=6.734, c=11.776 Å) has been determined by X-ray analysis. The results are discussed in relation to those of (NC)3C—X (X=—CH3, —Cl, —Br or —CN).

Notes: Homoisoflavanone. V. Kristalline und molekulare Struktur von (-)-7-O,-(p-Bromphenacyl)-eucomol. Absolute Konfiguration von (-)-EucomolZur Abklärung der absoluten Konfiguration von (-)-Eucomol wurde eine Röntgenstrukturanalyse des 7-O-p-Bromphenacylderivates durchgeführt. Auf Grund der anomalen Streuung von CuKα-Strahlung durch Brom liess sich 3S-Chiralität der Verbindung nachweisen. Die durch 372 Atomparameter beschriebene Struktur wurde mit 1745 Strukturfaktoren bis zu R = 0,071 verfeinert.

Notes: Kristalline und molekulare Struktur von HydroxybenzylpindololIm Zusammenhang mit einer Studie über die Konformation von adrenergen β-Blockern wurde die kristalline Struktur von Hydroxybenzylpindolol durch Röntgen-analyse bestimmt. Die Kristalle sind triklin, Raumgruppe P1, a = 10,041(2), b = 11,386(2), c = 10,131(2) Å, α = 114,03(2), β = 107,82(3), γ = 99,32(3)°, mit zwei Molekeln pro Zelle. Die Struktur wurde nach dem «Multisolution»-Prinzip gelöst und bis zu R=0,050 verfeinert. Die Molekeln sind im Kristall durch ein Netz von Wassertoffbrücken miteinander verbunden.

Notes: The dienal 14 and the ketone 19, both potential building blocks of maytansinoids, were synthesized starting from ethyl vanillate (2) via the aldehyde 9. It could be shown in a preliminary experiment that the dienal 14 can be coupled with 2-lithio-1,3-dithiane to afford compound 16 which exhibits the correctly substituted aromatic part of maytansine as well as its C(9) to C(15) moiety.

Notes: Alstonia scholaris: The structure of the indole alkaloid narelineBesides the known akuammidine, picralinal, picrinine and pseudoakuammigine a new indole alkaloid called nareline (M=352) was isolated from Alstonia scholaris R. BR., which belongs to the plant family of Apocynaceae. Its structure 2 was deduced by single crystal X-ray diffraction. 2 represents the absolute configuration. The spectroscopic data of 2 and its derivatives (Scheme 1) as well as their chemical behavior support this structure. In biogenetic sense nareline is related to the bases akuammiline (4) and picraline (5) (Scheme 2). In contrast to those the C-atom 5 is exocyclic and represents an aldehyde group which forms together with the oxygen atom of the N (4)-hydroxylamine group a cyclic half acetale. - By oxidation (CrO3/CH3COOH) of 2 the oxindol derivative 19 (oxonareline) is formed which contains a cyclic acetal as a partial structure element (Scheme 4).

Notes: Phytochemistry of genus Gentiana. XXII. Identification of new O-glucosides of mangiferin in Gentiana asclepiadea L.Two new O-glucosides of mangiferin (mangiferin-7-O-β-D-glucoside (1) and mangiferin-6-O-β-D-glucoside (2)) have been isolated from the leaves of Gentiana asclepiadea L. This is the first full structure elucidation of naturally occurring O-glucosides of C-glucosylxanthones. The known C-glucosylflavone, saponarin (5) was also identified.

Notes: Synthesis and amoebicid properties of emetin analogs. Analysis of the new compounds by 13C-NMR. B/C-cis or trans-fused (±) 1-alkyl-3-desethyl-emetin.New 1-alkyl-3-desethyl-emetines were prepared for pharmacological purposes.The usual emetine synthesis sequence applied to cis-1-alkylbenzo [a]quinolizidin-2-ones afforded new cis-1-alkyl-3-desethyl-emetines.The trans-fused isomers were also prepared.The relative configuration are determined by 1H- and 13C-NMR. spectra.

Notes: Phytochemistry of genus Gentiana XXI: The cinnamoyl-C-glucosylflavones and their O-glucosides in Gentiana punctata L.Three new (1-3) and three previously identified (4-6) cinnamoyl-C-glucosyl-flavones have been isolated from the leaves of Gentiana punctata L. The structures of the new compounds were established as: trans-cafeoyl-2″-iso-orientin-4′-O-β-D-glucoside (1), trans-feruloyl-2″-isovitexin-4′-O-β-D-glucoside (2) and trans-feruloyl-2″-isovitexin (3). Isoscoparine (8) and O-β-D-glucosyl-2″-iso-orientin (7) were also isolated and identified.

Notes: Zur Oxydation von Thebain mit m-Chlorperbenzoesäure, IIIDie Oxydation von Thebain (1) mit m-Chlorperbenzoesäure ist stark abhängig von den gewählten Reaktionsbedingungen. In unserem Fall wird neben 14-Hydroxy-codeinon (2) auch das bekannte, mono-acetylierte Diol 3 erhalten. Die Rückführung von 3 in 2 und die Verknüpfung mit dem bekannten Ketodiol 5, über das bisher nicht beschriebene 8, 14-Dihydroxydihydrothebain (4) wird gezeigt.

Notes: Debenzylation of 1-(3-benzyloxybenzyl)-1,2,3,4-tetrahydroisoquinolines 1, 6, 7 with hydrochloric acid and ethanol gave the corresponding phenolic isoquinolines 2, 8, 9 and tetrahydroprotoberberines 4, 12, 13. Compounds 2, 8, 9 on photolysis also gave, besides the expected noraporphines 3, 10, 11, the tetrahydroprotoberberines 4, 12, 13 [1-4] (Schemes 1 and 2). 6-Benzyloxy-1-(5-benzyloxy-2-bromo-benzyl)-1,2,3,4-tetrahydroisoquinoline (27a) containing no methoxy or methylenedioxy groups either in ring A or C does not give protoberberine during debenzylation; but 28, the debenzylation product of 27a, on photolysis gives both the noraporphine 29 and the tetrahydroprotoberberine 30 (Scheme 6), proving that during debenzylation of 1-(3-benzyloxybenzyl)-1,2,3,4-tetrahydroisoquinolines containing additional methoxy or methylenedioxy groups, the necessary formaldehyde comes from the latter groups. During photolysis both the methoxy groups (methylenedioxy groups) and the C(3) atom of the tetrahydroisoquinoline moiety provide the formaldehyde. Veratrole under debenzylation and photolytic conditions and tetrahydroisoquinoline under the latter condition also give rise to formaldehyde (Schemes 8 and 10).The novel bromohomoprotoberberine 43 along with 42 was formed during debenzylation of the 1-phenethyl-1,2,3,4-tetrahydroisoquinoline 41. Photolysis of 42 yielded the novel nor-homoaporphine 44, in addition to 43; the latter was debrominated to give the homoberbine 45.

Notes: Metabolism of Acetylenic Monocarboxylic and Dicarboxylic AcidsFeeding of acetylenic monoacids with chain length of 11 to 18 C-atoms to rats led to excretion of dicarboxylic acids with retained triple bonds. 10-Octadecynoic acid led to the formation of metabolites with even and odd number of C-atoms, suggesting in addition to established ω- and β-oxidation an α-oxidative pathway.

Notes: Distribution and Metabolism of Octadec-9-ynoic acid in RatsOctadec-9-ynoic acid (stearolic acid) fed to rats leads to the metabolic excretion of six dicarboxylic acids with retained triple bond. The main metabolic steps are ω-, β-, and presumably α-oxidation. Feeding of 14C-stearolic acid proves that the α-oxidative steps involves the methyl end of the original acid. It could further be shown that this acid is incorporated partially in the body lipids. To a substantial degree it is totally oxidized and expired as 14C—CO2.

Notes: The Carbo(3-phenylpyrazol-5-yl-hydrazonoyl) halides 1a,b react with active methylene compounds to yield the 1-(3-phenylpyrazol-5-yl)-pyrazole derivatives 2a-k (Scheme 1). The acyclic intermediates 3a,b could be isolated from reaction of 1a,b with acetylacetone, thus establishing the substitution mechanism for these reactions.Compounds 1a, b reacted with carbon disulfide, phenyl isothiocyanate, methyl cyanide, and with p-chlorobenzaldehyde to yield the corresponding heterocyclic derivatives 5-8, respectively (Scheme 2).The behaviour of compounds 2 with hydrazine hydrate is reported.

Notes: Apart from the well-known constituents (+)-β-selinene (2), (-)-β-elemene (4), (+)-β-costol (7), (-)-caryophyllene (17), and (-)-elemol (19) the following sesquiterpenoids have been isolated for the first time from costus root oil (Saussurea lappa CLARKE): (-)-α-selinene (1), (+)-selina-4, 11-diene (3), (-)-α-trans-bergamotene (5), (-)-α-costol (6), (+)-γ-costol (8), (-)-elema-1,3,11 (13)-trien-12-ol (9), (-)-α-costal (11), (+)-γ-costal (12), (+)-γ-costal (13), (-)-elema-1,3,11 (13)-trien-12-al (elemenal, 14), (-)-(E)-trans-bergamota-2, 12-dien-14-al (15), (-)-ar-curcumene (16), and (-)-caryophyllene oxide (18). Compounds 6, 8, 9, and 13 are new sesquiterpenoids. IR. and NMR. spectra of 12 sesquiterpenoids are reproduced.

Notes: (E)-9-Isopropyl-6-methyl-5,9-decadien-2-one (1a), a terpenoid C14-ketone with a novel skeleton, was isolated from costus root oil (Saussurea lappa CLARKE) and its structure established by a two-step synthesis from thuja ketone (2). The possible role of the new compound as an intermediate in the biosynthesis of the irones is discussed.

Notes: The Bromination of Push-Pull-Olefins. II. Structure Elucidation of the Bromination ProductsBromination of 3-dialkylamino-acroleins 1a, b as well as of 4-dialkylamino-3-buten-2-ons 1c, d gives O-protonated produkts 2 with all-trans configuration of the (N—C—C—C—O)-skeleton. The structure of these hydrobromides 2 is confirmed by 1H- as well as by 13C-NMR. evidence.

Notes: Polymer Bound Cinchona Alkaloids as Catalysts in the Michael ReactionThree insoluble chiral polymers (6, 7 and 8) were prepared by functionalization of copoly(styrene -2% divinyl benzene) followed by reaction with quinine (9) or dihydrocupreine (10). Their utility as catalysts in the reaction between methyl indane-1-one-2-carboxylate (13) and 3-butene-2-one (14) was studied. Table 1 (runs 2-6 and 8) shows that the Michael-adduct 15 was formed in good chemical but low optical yields, independent of the chiral polymer used. These results are compared with those of the Michael reactions in the presence of the monomeric bases quinine (9), O-acetyl-quinine (11) and eucipine (12) (runs 1, 7 and 9).

Notes: Experimental valence ionisation energies of 143 hydrocarbons, CnHm, have been determined from their He (IIα) (40.80 eV) and He (Iα) (21.22 eV) excited photoelectron spectra. Ionization energies, usually up to 26 eV are given in tabular form for 108 hydrocarbons with n≤6, together with their (tentative) assignment. The ionization energies up to approximately 25 eV, of 35 selected hydrocarbons with 7≤n≤10, are presented by means of their He (IIα) photoelectron spectra.

Notes: Reactions of 3-dimethylamino-2,2-dimethyl-2H-azirine with phenols and aryl halidesThe reactions of 3-dimethylamino-2,2-dimethyl-2H-azirine (1) with phenols are described in chap. 1. The azirine 1 reacts with the 2-formyl- and 2-acetylphenols 5-8 to yield the N′-methylidene derivatives of 2-amino-N,N-dimethyl-isobutyramide 9-12 (Scheme 2, tautomeric form b). These products are in equilibrium with the tautomeric quinoide forms 9a-12a. Under similar conditions 4-hydroxybenzaldehyde did not react with 1. Reaction of 1 with 4-hydroxycoumarine (13) gives the 4-amino-coumarine 14 (Scheme 2). The mechanism of these reactions is analogous to the previously reported one for the reaction of 1 with cyclic enolisable 1,3-diketones [2] [3].Activated phenols with pKa-values 〈 8, e.g. 2- and 4-nitrophenol, 2,4-dinitrophenol and pentachlorophenol, undergo addition reactions with 1 in boiling benzene solution to give the aniline derivatives 15-18 (Scheme 3). A reaction mechanism is given in Scheme 3: after protonation of the azirine 1 followed by attack of the phenolate ion at the amidinium-C-atom, the intermediate of type e undergoes a rearrangement to the spiro-Meisenheimer complexes of type f. Ring opening leads to 15-18. A similar reaction is observed for 2,4-dinitro-thiophenol and 1, giving 2-(N′-(2,4-dinitrophenyl)amino)-N,N-dimethyl-isobutyrothioamide (19).The azirine 1 reacts with the more acidic 2,4,6-trinitrophenol (picric acid) to yield 3,3,6,6-tetramethylpiperazine-2,5-bis(N,N-dimethyliminium) dipicrate (21, Scheme 4). The methacrylamidinium salt 22 is the only product (97% yield) in the reaction of 8-hydroxy-5,7-dinitroquinoline and 1 in acetonitrile solution. The reaction of 1 with picric acid can be explained in a similar way as the previously reported one with strong acids (cf. Scheme 1, [1] [3] [5]). An alternative mechanism without formation of the 1-aza-allylcation c is postulated in Scheme 5, together with a mechanism which could explain the exclusive formation of 22 in the reaction of 1 with 8-hydroxy-5,7-dinitroquinoline.In chap. 2 a few reactions of the azirine 1 with aryl halides are reported. In the reaction with 2,4-dinitrofluorobenzene it is shown by UV. and NMR., that m,n and o are intermediates (Scheme 6). Working up the reaction mixture with water, hydrogen sulfide or benzylamine leads to the aniline derivatives 17, 19 and 26, respectively. With picryl chloride and 8-hydroxy-5,7-dinitroquinoline the azirine 1 undergoes a nucleophilic aromatic substitution to afford the intermediates p and q, which via deprotonation and ring opening give acrylamidine derivatives (27 and 29, Scheme 7 and 8). The steric hindrance in p and q between the aziridine ring and the two groups in o-position could be the reason for the different behaviour of the intermediates n and p or q (cf. Schemes 6 and 8).

Notes: (1)The existence of a main regulation site(s) of the cholesterol synthesis located after the squalene formation is demonstrated by cholesterol feeding with labelled glucose, acetate, mevalonate as precursors and by measuring the incorporation rates into cholesterol, squalene, ubiquinones, and fatty acids in rat liver in vivo.(2)By administration of labelled squalene in vivo it is shown that the isoprenic synthesis is inhibited between squalene and lanosterol but that other regulation site(s) after the lanosterol formation must exist.(3)A regulation site of the cholesterogenesis in rat liver located after the squalene synthesis is also shown after a lipogenic diet administered during 5 days. The cholesterol synthesis is thus reduced to about one third of the control rats. Another regulating site controlling the utilization of acetylcoenzyme A for the synthesis of mevalonate is also shown to exist. No indication was obtained for a regulating influence located between mevalonate and squalene.

Notes: The ligand exchange MX5·L + *L⇌MX5·*L + L for the octahedral adducts MX5·L, in an inert solvent (CH2Cl2 or CHCl3) with neutral ligands, proceeds via a dissociative D mechanism when M = Nb, X = Cl and L = phosphoryl compound. A dissociative interchange Id mechanism is suggested when M = Nb or Ta, and X = F. A first order rate law and positive values for ΔS* (+4 to +14 cal K-1 mol-1) are observed for the exchanges on the pentachloride adducts. However, a second order rate law and large negative values for ΔS* (-15 to -24 cal K-1 mol-1) are found for the intermolecular neutral ligand exchange (measured by 1H-NMR.) and for the intramolecular fluorine exchange (measured by 19F-NMR.) reactions on the pentafluoride adducts. The fluorine exchange is 2 to 5 times faster than the ligand exchange. The exchanges, on the pentachloride and on the pentafluoride adducts, are slowed down with increasing donor strength of the phosphoryl compound.

Notes: Reactions of Steroids with Dialkylaminosulfur Trifluorides. I. 11β-Hydroxysteroids.Reactions of three types of 11β-hydroxy steroids with dialkylaminosulfur trifluorides (DAST) have been studied. 9Δ-unsubstituted 11-alcohols are dehydrated with DAST to Δ9(11)-unsaturated compounds under very mild conditions. 9α-Chloro-11β-hydroxy steroids are quantitatively fluorinated in position 11 yielding the known 9α-chloro-11β-fluoro derivatives. Finally, 9α, 11Δ-fluorohydrins at 0-25° are selectively transformed with DAST into Δ11-9α-fluorides. When the latter reaction is run at lower temperature, the corresponding 11-piperidinesulfinates, products of partial hydrolysis of the alkoxy-dialkylaminosulfur difluoride intermediates postulated by Middleton, can be isolated in high yields. A rational explanation of the results is presented.

Notes: The investigation of the convergence properties of matrix iterative processes usually involves test matrices of high order. This fact may prohibit an analytic approach to the problem. In this paper a method is presented which converts the multidimensional test procedure into a scalar one. The method is presented in conjunction with the problem of matrix orthogonalization which exists in Strapdown Inertial Navigation. Three examples are presented in which the convergence of matrix orthogonalization techniques is investigated. The examples demonstrate the use of the unidimensional convergence test in determining the order of the processes and in finding sufficient conditions for convergence. Numerical results are presented.

Notes: This paper contains an algorithm for the ordering of elements in the finite element method, which can be utilized in the Non-assembly Method of the author and in the Frontal Solution Method of B. M. Irons.

Notes: Based on a generalized complementary energy principle the derivation of the element matrices is presented for calculation of natural frequencies. The degrees-of-freedom are not defined on nodal points but in an abstract way. No restrictions about the number of interpolation functions in the interior and at the boundaries of the element have been introduced. The exact solution of the discretized element equations leads to the dynamic stiffness matrix while the approximate solution results in a linear eigenvalue problem. Plate bending problems are used to study the convergence of frequencies depending on the degrees of interpolation functions within the element and on its boundaries and on the number of elements.

Notes: A Block-Stodola eigensolution method is presented for large algebraic eigensystems of the form AU = λBU where A is real but non-symmetric. The steps in this method parallel those of a previous technique for the case when both A and B were real and symmetric. The essence of the technique is simultaneous iteration using a group of trial vectors instead of only one vector as is the case in the classical Stodola-Vianello iteration method. The problem is then transformed into a subspace where a direct solution of the reduced algebraic eigenvalue problem is sought. The main advantage is the significant reduction of computational effort in extracting a subset of eigenvalues and corresponding eigenvectors. Theorems from linear algebra serve to underlie the basis of the present technique. Complex eigendata that emerge during iteration can be handled without doubling the size of the problem. Higher order eigenvalue problems are reducible to first order form for which this technique is applicable. The treatment of the quadratic eigenvalue problem illustrates the details of this extension.

Notes: We suggest an exercise which illustrates many of the fundamental ideas of finite elements, and is nevertheless easily programmed and quickly solved. It is governed by a partial differential equation on a circular region, but by maintaining symmetry the stiffness matrix becomes small and tridiagonal. The accuracy of linear elements can be studied in detail, and a straightforward extension leads to the eigenvalue problem, elements of higher degree, numerical integration, isoparametric elements, and a simple example in plasticity.

Notes: A novel method is proposed for the numerical computation of Fourier coefficients in the range of higher frequencies for which hitherto no practical method was available. The accuracy of the results obtained by application of this method is discussed, and bounds of a correction term are determined accordingly. An example from the field of Diesel engine research is given, and the computed spectrum is compared with the spectrum recorded by an electronic harmonic analyzer.

Notes: Finite element formulations based on the Galerkin and variational principles have been developed for the self-adjoint and non-self-adjoint problems represented respectively by the flow and convective-dispersion equations in the cylindrical polar system of co-ordinates. The formulation based on the variational principle is shown to be restricted to dispersion-dominant transports only. The Galerkin method is demonstrated to be more versatile and free from convergence and stability problems. The computational scheme based on the Galerkin principle is shown to be equally valid for both convection and dispersion dominant transports. The numerical results obtained are verified with known analytical solutions. It is concluded that the suggested scheme can be used in solving a variety of field problems involving groundwater dispersion.

Notes: The indirect design problem for compressible fluid flow in a channel determines the physical shape of the channel from the prescribed flow on the channel boundary. In this paper, a global variational method for the solution of this problem is described.The non-linear equations are solved by iteration; at each step of this iteration the solution to the equations (which are now linear) is found by a global variational method. The variational method differs from conventional methods in that the trial function does not satisfy the prescribed boundary conditions, but the method reproduces the conditions on the boundary.Results are presented for various physical quantities associated with the channel.Some comments are made on the extensions of these methods to supersonic flow and to the realistic cascade design problem.

Notes: A complete analytical analysis of three-dimensional, quadratic displacement tetrahedron elements is presented. The results show that the element stiffness can readily be obtained from the much simpler stiffness matrix of the linear displacement element. Thus, the task of obtaining the matrix of the quadratic displacement element is, in effect, reduced to finding that of the linear displacement element.The analysis has been made possible only by using a symbolic manipulation language (PL/I-FORMAC) on a computer. A rather general program for computer-aided basic element analysis is presented. It seems that the extremely effective tool of symbolic manipulation has hardly been used until now in mechanics.

Notes: A direct numerical method is presented for the solution of classes of non-linear, singular Volterra integral and integro-differential equations of the types where y is the unknown and the Fs and Gs are given but to a large extent arbitrary functions of their arguments. The adaptation of the method to other equations, in particular with different kernels, is immediate.