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Notes: Isosweroside, a New Secoiridoid Glycoside from the Roots of Sambucus ebulus L. (Caprifoliaceae)The paper describes the isolation and structure elucidation of isosweroside (6-(β-D- glucopyranosyloxy)-methyl-9-vinyl-2,8-dioxabicyclo[3.3.1]non-6-en-3-one), the first Valeriana-type secoiridoid glycoside from the roots of Sambucus ebulus L. along with the two known glycosides ebuloside and morroniside.

Notes: Synthesis of 3-Deoxy-3-(hydroxyamino)furanose AcetalsReduction of sugar ketoximes with NaBH3CN under acidic conditions constitutes a good synthetic pathway to deoxy(hydroxyamino)sugar derivatives. These compounds which are useful building blocks for the preparation of analogs of various classes of biologically important carbohydrates are reasonably stable.

Notes: (R)-3-Hydroxybutyric acid (from the biopolymer PHB) and pivalaldehyde give the crystalline cis - or (R,R)-2-(tert-butyl)-6-methyl-1,3-dioxan-4-one (1a), the enolate of which is stable at low temperature in THF solution and can be alkylated diastereoselectively (→3, 4, 5, and 7). Phenylselenation and subsequent elimination give an enantiomerically pure enol acetal 10 of aceto-acetic acid. Some reactions of 10 have been carried out, such as Michael addition (→11), alkylation on the CH3 substituent (→13), hydrogenation of the C=C bond (→1a) and photochemical cycloaddition (→16). The overall reactions are substitutions on the one stereogenic center of the starting β-hydroxy acid without racemization and without using a chiral auxiliary.

Notes: The structure of the α-chloronitroso ether 1, obtained from the hydroximolactone 2 and tert-butyl hypochlorite (89%), was established by X-ray crystallographic analysis. The [4 + 2] cycloadditions of 1 with the dienes 3 and 8-11 led to the N-unsubstituted 3,6-dihydro-2H-1,2-oxazines 6 and 12-16 in high enantiomeric excess (Table 1). Due to the additional α-alkoxy group, the reactivity of 2 is much superior to the one of known α-chloronitrosoalkanes. The reactive conformation of 1 was deduced from the X-ray analysis as well as the high diastereoselectivity of the cycloadditions. The importance of the α-alkoxy group was evidenced from the similar reactivity of the racemic α-chloronitroso ethers 25-27 which were prepared from the hydroximo ethers 28-30 and tert-butyl hypochlorite.

Notes: 1-C-Nitroglycals. Preparation and Reaction with Some Nitrogen NucleophilesAcetylation of the 1-deoxy-1-nitromannopyranoses 2 and 6 was accompagnied by spontanous β-elimination to give the 1-C-nitroglucals 3 and 7, respectively, while acetylation of the gluco- and galacto-configurated 1-deoxy-1-nitropyranoses 8 and 14 gave the acetates 9 and 15, respectively (Scheme 1). The acetylation of the ribo- and arabino-configurated 1-deoxy-1-nitrofuranoses 19 and 21 also occurred without β-elimination to give the acetates 20 and 22, respectively (Scheme 2). Mild base treatment of the previously described O-acetylnitro-β-D-glucose 4, the O-acetylnitro-β-D-pyranoses 9 and 15, and the O-acetylnitro-β-D-furanoses 17, 20, and 22 gave the 1-C-nitroglycals 3, 10, 16, 18 and 23, respectively (Scheme 1 and 2). The previously obtained 1-C-nitroglucal 3 was deacetylated by treatment with MeOH in the presence of KCN or sodium m-nitrophenolate to give the free nitroglucal 5. Deacetylation of the benzylidene protected 1-C-nitroglucal 10 (MeOH, NaOMe) gave the 4,6-O-benzylidene-1-C-nitroglucal 11 and traces of the 2-O-methyl-1-C-nitromannoses 12 and 13. The UV, IR, 1H-NMR and 13C-NMR spectra of the 1-C-nitroglycals are discussed. In solution, the 1-C-nitroglycals 1, 5, 7, 10, 11, and 16 adopt approximately a 4H5- and 3 a flattened 4H5 conformation. The structure of 5 was established by X-ray analysis. In the solid state, 5 adopts a sofa conformation, which is stabilized by an intramolecular H-bond. The β-addition of NH3 to the 1-C-nitroglucals 7 and 10 was followed by an O→ N acetyl migration to give exclusively anomeric pairs of the N-acetyl-1-nitromannosamine derivatives 24/25 and 26/27, respectively (Scheme 3). The β-addition of methylamine, octadecylamine, and tryptamine to the 1-C-nitroglucal 11 also stereoelectronically controlled and gave the crystalline N-alkyl-1-nitromannosamines 28, 29, and 30, respectively. The stereoelectronically controlled β-addition of NH3 to the 1-C-nitrogalactal 16, followed by acetylation, yielded exclusively the talosamine derivative 31, while the reversible β-addition of azide ions to 16 gave the anomeric 2-azido-1-nitrogalactoses 32 and 33. The β-addition of azide ions to the 1-C-nitroglucal 1 led to the 2-azido-1-nitromannose 34. In the presence of excess formaldehyde, this addition was followed by a Henry reaction. Chromatography of the crude product was accompagnied by solvolytic removal of the NO2 group to give the 3-azidomannoheptulose 35 in high yields (Scheme 4).

Notes: The complexation properties of the open-chain N2S2 ligands 1-4 are described and compared to those of analogous N2S2 macrocycles 5-7. With Cu2+, the open-chain ligands give complexes with the stoichiometry CuL2+ and CuLOH+, the stabilities and absorption spectra of which have been determined. The ligand field exerted by these ligands is relatively constant and independent of the length of the chain. With Cu+, the species CuLH23+, CuLH2+, and CuL+ were identified and their stabilities measured. The redox potentials calculated from the equilibrium constants and measured by cyclic voltammetry agree and lie between 250 and 280 mV against SHE. The comparison between open-chain and cyclic ligands shows that (1) a macrocyclic effect is found for Cu2+ but not for Cu+, (2) the ligand-field strength is very different for the two types of ligands, and (3) the redox potentials span a larger interval for the macrocyclic than for the open-chain complexes.

Notes: The chemical synthesis of the ribo-hexamer C-A-A-C-C-A has been achieved by two different routes applying the phosphotriester approach and using the (p-nitrophenyl)ethyl group for phosphate protection. The 2′-hydroxy groups as well as the terminal 2′,3′-diol function have been blocked by the (tert-butyl) dimethylsilyl group as permanent protection throughout all the synthetic steps with great success. Final deblocking of all protective groups could be performed with 80% yield to give the hexamer 23. The various protected intermediates have been characterized by elemental analysis and UV spectra.

Notes: The 1,4-endoperoxide, prepared from 3-(4-methylnaphth-1-yl)propanal by photo-oxygenation in CH2Cl2, gave on treatment with Amberlyst-15®, 3,10b-epidioxy-2,3,4a,10b-tetrahydro-6-methyl-1H-naphtho[2,1-b] pyran in 85% yield. Its structure was determined by X-ray crystal structure analysis. The 1,2,4-trioxane moiety is locked in a twist-boat conformation with trans fusion to the parent six-membered ring. The 1,4-endoperoxides of the methyl, butyl, and phenyl ketone analogues of the aforementioned aldehyde underwent similar acid-catalyzed rearrangement to the corresponding bridged bicyclic trioxanes in 94, 47, and 48% yields, respectively.

Notes: The low-temperature addition of tertiary phosphites to [(allyl)Fe (CO)4]+X- complexes proceeds regio- and stereospecifically and produces metal-coordinated β-olefinic trialkoxyphosphonium ions. These can be converted by various routes into the uncomplexed phosphonium salts or phosphonates. Similar reactions of acyclic [(dienyl)Fe(CO)3]+X- compounds give metal-coordinated (2,4-dien-1-yl)trialkoxyphosphonium salts or dialkyl (2,4-dien-1-yl)phosphonates. The mechanisms and their relationship to the classical Michaelis-Arbuzov reaction are discussed. The new compounds are characterized, if possible, by 1H-, 13C-, and 31P-NMR spectra. The new phosphonium salts and phosphonates, potentially useful for Wittig-Horner reactions, are difficult to obtain by conventional routes.

Notes: Preferred conformation, orientation, and accumulation of substance P on a neutral hydrophilic-hydrophobic interface was estimated and extrapolated to interactions with neutral and anionic lipid bilayer membranes according to our general procedure. Nine residues at the C-terminus were predicted to be transferred to the hydrophobic phase as an α-helical domain, oriented quite perpendicularly on the membrane surface. The N-terminal residues remained in the aqueous phase with their charges exposed to H2O. The molecular amphiphilic moment vector was strong (338 arbitrary units) and pointed its hydrophilic end towards the N-terminus, only 15° away from the helix axis. The molecular electric dipole moment vector was also strong (124 debye) and pointed its positive end towards the N-terminus, only 9° away from the helix axis. Thus, it reinforced the effect of the amphiphilic moment of a peptide intruding into the membrane dipole layer. The estimated dissociation constant for the equilibrium between membrane-bound and free substance P was Kd ≍ 46 mM for neutral membranes, and Kd ≍0.43 mM for anionic membranes with a Gouy-Chapman surface potential of -40 mV. Thus, substance P behaved similarly to dynorphin A and adrenocorticotropin peptides which insert their N-terminal message segments as perpendicularly oriented helical domains into membranes, whereas their C-terminal address segments remain in the aqueous phase as random coils. Substance P is the first instance of a neuropeptide which is expected to insert a C-terminal message into lipid membranes.

Notes: Comparative CD studies with substance P (1), [Leu9]substance P ([Leu9]-1), and their shorter peptide segments supported the membrane structures predicted for substance P and [Leu9]substance P. They indicated that the C-terminal segments (from residue 3 or 4 onward) can adopt α-helical conformations in hydrophobic environments and on lipid membranes. The N-terminal segment, (residues 1-4) had a poly(proline)-like conformation in aqueous and hydrophobic surroundings. Residues 3 and 4 (Lys-Pro) appeared to belong to both domains and bring about the transition between the two. The estimated free energies of transfer for 1 and [Leu9]-1 from their random conformations in H2O to their partially helical conformations on an aqueous-hydrophobic interface are too small to allow detectable interaction with neutral lipid membranes at low concentrations. The two peptides should, however, interact detectably with anionic membranes because of favourable Boltzmann distribution factors. This prediction was shown to be correct for liposomes prepared from 1,2-dioleoyl-sn-glycero-3-phosphocholine (neutral) and phosphatidylserine (anionic).

Notes: IR data of the neuropeptide substance P (1) and its synthetic segments des-(Arg1-Gln6)-substance P (6), des-(Arg1-Pro4)-substance P (4), des-(Arg1-Lys3)-substance P (3), and des-Arg1-substance P (2) indicate predominant β-structures in the solid state and α-helical structures in CF3CH2OH (amide I band shape analysis). In MeOH, the spectra of 1 suggest a partly helical structure. On membranes prepared from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, a C-terminal α-helix consisting of 8 or 9 peptide bonds appears to be induced (IR attenuated total reflection studies). Its perpendicular orientation on the membrane is suggested by the dichroic ratios of the amide-I and -II bands. This study is consistent with our CD experiments and lends support to the membrane structure of 1 predicted from the estimated amphiphilic moment, hydrophobic-association constant, and helix length.

Notes: Enantiomerically pure β-necrodol (1) and its 1-epimer 16 have been synthesized starting from aldehyde 5. The two key steps are an asymmetric conjugate addtion/Mannich reaction tandem (10→12) and a type-II-magnesiumene cyclization/oxidation sequence (14→1 + 16).

Notes: Lipophilic neutral carriers were synthesized which show Li+/Na+ selectivities of up to ca. 80 in highly lipophilic liquid membranes. The sensor membranes exhibit improved response times and increased lifetimes as compared to systems described earlier. They allow reliable measurements of Li+ in blood serum within the clinical concentration range. A 1:1 Li+/ionophore complex of one representative (N,N,N′,N′-tetracyclohexyl-5,5-dimethyl-3,7-dioxaazelaamide) has been prepared, and its structure was elucidated by X-ray analysis.

Notes: (2S, 3R, 4R, 6R)-2,3,4-Trihydroxy-6-methylcyclohexanone from Two Strains of ActinomycetesA tetrazolium-blue positive compound was isolated from two strains of acinomycetes. Its constitution and relative configuration 1 were determined by spectroscopic methods, and the absolute configuration by degradation to (+)-(R)-methylsuccinic acid.

Notes: Isolation and Structure Elucidation of DifferolideFrom cultures of a new actinomycete, Streptomyces aurantiogriseus (PREOBRAZHENSKAYA 1975), strain Tü 3149, a compound C12H12O4 was isolated, which enhances the formation of aerial mycelium and spores of Streptomyces glaucescens. The structure determined by X-ray diffraction studies was that of racemic dilactone 1 ((±)-differolide).

Notes: Carbophilic Additions of Organocuprates and 1,3-Thiazole-5(4H)-thionesOrganocuprates and 1,3-thiazole-5(4H)-thiones 1 react in THF at 0° via carbophilic addition onto the C—S bond to give 4,5-dihydro-1,3-thiazole-5-thiols 3 (Scheme 3). This observation is in marked contrast to the previously described reaction of organolithium compounds and 1, which undergo a thiophilic addition onto the exocyclic S-atom. As an exception, treatment of the 1,3-thiazole-5(4H)-thione 1a with tert-butyl cuprate leads to 7a (Scheme 3).

Notes: 3β-Hydroxy[21-14C]5β-pregn-8(14)-en-20-one (17) was prepared from chenodeoxycholic acid (1a). The synthetic sequence involved: (i) degradation of the bile-acid side chain to an etianic acid; (ii) formation of the 8(14)-double bond; (iii) inversion of the configuration at C(3); (iv) construction of the acetyl side chain at C(17) with the required isotopic label at C(21). Structures of all described products were confirmed by chemical and spectroscopic (IR, 1H-NMR, 13C-NMR, MS) methods.

Notes: New Derivatives of 1,6-Methano[10]annulene by Rearrangement of Trimethylsilyl GroupsOxidation of derivatives of trimethylsilyl-substituted bicyclo[4.4.1]undeca-1,3,5,7-tetraenes 1-3 leads to 1,6-methano[10]annulenes. In the case of 2 and 3a, rearrangement of the trimethylsilyl group takes place. This rearrangement can be used to prepare 2,9-disubstituted 1,6-methano[10]annulenes.

Notes: Cyclometallated complexes of the type cis-bis(2-phenylpyridine)platinum(II) (C22H16N2Pt) and cis-bis(2-(2′-thienyl)pyridine)platinum(II) (C18H12N2S2Pt) undergo thermal or photochemical oxidative addition (TOA or POA) reactions with a number of substrates. TOA (with CH3I, CH3CH2I etc.) yield mixtures of several isomers which rearrange slowly (within ca. one week at room temperature) to one of the possible cis-isomers. CH2Cl2, CHCl3, or (E)—ClCH=CHCl, e.g., do not react thermally. POA yield directly complexes of Pt(IV) with the halide and a σ-bonded C-atom in cis-position. The configuration, as assigned by extensive use of 1H-NMR data, can be characterized for the two chelating ligands C … N and C′ … N′ by C,C′-cis; N,N′-cis and C(chelate), Cl-trans.

Notes: The synthesis of the five-membered cyclic phosphorodiamidic-acid derivatives 10 and 11 as well as the preparation of the six-membered cyclic phosphates 18, 19, 22-25, and phosphoramidates 27-32 is described. The effects of these conformationally restricted platelet-activating factor analogs on rabbit platelet aggregation are briefly discussed. The 2-oxo-1,3,2-dioxaphosphorinanes 19, 25, and 30 were found to be equally potent platelet-activating factor antagonists as the known thiazolium salt 33.

Notes: Metabolites of 1,5-Dihydroimidazo[2,1-b ]quinazolin-2(3H)-ones. Preparation and Reactions of Some 1,5-Dihydro-3-hydroxyimidazo[2,1-b]quinazolin-2(3H)-onesHydroxylated 1,5-dihydroimidazo[2,1-b]quinazolin-2(3H)-ones 2-4 and 6 were isolated as metabolites of imidazoquinazolinones 1a and 1b, respectively. The synthesis of 1,5-dihydro-3-hydroxy-3-methylimidazo[2,1-b]quinazolin-2(3H)-ones 3, 4, and 6, and the preparation of some derivatives thereof is described.

Notes: [2 + 2] Cycloaddition of (menthyloxy)methylketene (2) to cis-ethyl propenyl ether showed a ca. 3:1 diastereo-selectivity. A two-step transformation of the thermodynamically more stable adduct 4 furnished the (2R*, 3R*)-compound 5 with ca. 50% e.e. (Scheme 1). The analogous reaction sequence with cis- benzyl 1-hexenyl ether (9) and 2 showed a ca. 5:1 diastereoselectivity in 10 and 11 (Scheme 2). Absolute configuration of C(3) and C(4) in 11 has been proved by converting it to (-)-blastmycinone. Accordingly, the preferred transition state has been deduced as 15.

Notes: Combined NOE and Decoupling Experiments for the Selective H-NMR Detection: Application to a Stereochemical ProblemThe successful solution of complex stereochemical problems by NMR methods often requires scalar (J) and dipolar (NOE) data. A modern method, improved with respect to sensitivity and selectivity, which yields both scalar and dipolar informations is proposed, and an application to configurational analysis is demonstrated. The method is based on NOE effects for the detection of selected protons and homonuclear decoupling for improved resolution.

Notes: The two tetraazamacrocycle-N,N′,N″,N‴-tetraacetic acids H4dota and H4teta form with Ni2+, Cu2+, and Zn2+ (M2+) mononuclear complexes MLH2 and M′[ML], M′ being an alkaline earth ion. The structures of Ni(H2dota) and Cu(H2dota) have been solved by X-ray structure analysis. The metal ions are in a distorted octahedral geometry coordinated by four amino N-atoms and two carboxylates. In the case of Cu2+, the distortions are more pronounced than for Ni2+ indicating that the Jahn-Teller effect is operating. Starting from these two structures, the coordination geometry of the other complexes is discussed using VIS and IR spectra.

Notes: The three ligands H4dota, H4teta, and H4heta give binuclear complexes with Cu2+ and Ni2+, the spectral properties of which have been studied. The structures of Cu2(dota)·5H2O and Cu2(teta)·6H2O have been established by X-ray diffraction analysis.

Notes: Mono-N-substituted azamacrocycles 2-7, containing a carboxyalkyl or carboxyaryl side-chain, are obtained by reacting a five-fold excess of the macrocycle with 1 equiv. of a suitable halogenocarboxylic acid in alkaline aqueous EtOH. For halogenocarboxylic acids, which easily lactonize under alkaline conditions, a variant with the corresponding ester or nitrile as alkylating agent is also described. The salient point of this synthesis lies in the use of an excess of the macrocycle over the alkylating agent, thus reducing the amount of polyalkylation to a minimum, and in the easy separation of the excess of unreacted educt from the aminocarboxylic acid. These new ligands form Ni2+ and Cu2+ complexes, the spectral properties of which have been studied. In the case of the Cu2+ complexes with ligand 2, 3, and 6, a pH-dependent color change is observed. This is explained with an equilibrium between a species, in which the carboxylate group is bound to the metal, and one, in which it is protonated and non-coordinated. In the case of the Ni2+ complexes with the same ligands, only the species with a coordinated carboxylate was observed. In the Cu2+ and Ni2+ complexes with ligands 4 and 5, however, the carboxylate group does not coordinate at all, because of the length or the special structure of the chain.

Notes: Substituent Transformations on TriaziridinesSeveral novel triaziridines were prepared by substituent transformations starting from the known dialkyl-triaziridine-carboxylates 1a-c, with the aim to study the influence of the substitution pattern on the properties of the triaziridine ring. The dialkyl-triaziridines 2a-c were obtained by (t-BuO-)-mediated demethylation and decarboxylation and the dialkyl-triaziridine-methanols 4a-c by LiAlH4 reduction. Further reduction of the tosylates of 4a, b with LiAlH4 gave the methyl-dialkyl-triaziridines 3a, b. The dialkyl-triaziridines 2a, c could not be N-methylated directly with CH3I, but the anions 10a, c, obtained from 2a, c with CH3Li, yielded 3a, c. N-Methylation of 2a with (CH3)3OBF4 did not afford 3a but rather the methyl-triaziridinium salt 11. The dialkyl-triaziridine 2c has pKa 〉 14, its protonated species 〈 2. A concept that the electron pairs on the triaziridine N-atoms are more strongly localized than on amine N-atoms explains (a) that the dialkyl-triaziridine 2c is hardly basic, (b) that the LiAlH4 reductions of the esters 1 stop at the stage of the methanols 4, and (c) that the methanols 4a, b do not cleave like aminomethanols.

Notes: The solvolysis rates and products of 4- and 5-exo-substituted 2-exo- and 2-endo-norbornyl tosylates 9 and 10, respectively, are reported. The logarithms of the rate constants (log k) correlate linearly with the inductive constants σIq for the substituents. A comparison of the reaction constants p1 for the 4-, 5-, 6-, and 7-substituted 2-exo- and 2-endo-tosylates 9, 10, 1, and 2 respectively, indicates that inductivity is higher for 2-exo-ionization than for 2-endo-ionization in all series. This observation is attributed to the more favorable alignment of neighbouring C-atoms for dorsal participation in exo-ionization, especially, in the case of C(6).

Notes: The He(Iα) PE spectra of the two pairs of 1(Ph)-3 and 2-4 have been recorded and assigned by comparison with spectra of related molecules, or by using simple MO arguments. This analysis shows that the PE spectra are in agreement with the assumption that the twist angles observed in the crystalline state are more or less conserved in the gas phase. The observed first adiabatic ionization energies IIa allow the calculation of the molar reaction enthalpy ΔrHmθ which accompanies the enolization of the radical cations of the title compounds. It is found that ΔrHmθ ≍ --70 kJ mol-1 is roughly the same for both keto/enol pairs, in qualitative and quantitative agreement with expectation. These results complement and correct ionization energies determined previously by mass spectrometric methods and conclusions based on them.

Notes: N-Acetylneuraminic acid (1) can be transformed into the methyl α-D-ketoside 2 which, by reaction with methanesulfonyl chloride, yields the corresponding 4-O-mesylate 3 and the 4,7-di-O-mesylate 4 as a by-product. Compound 3 reacts with Nal giving the 4-deoxy-4-iodo compound 5 with equatorial orientation of the I-atom. As second product, the dihydrooxazole 6 is produced. Catalytic hydrogenation of 5 is followed by ester cleavage and removal of the isopropylidene group yielding the methyl α-D-ketoside 8 which affords the title compound, N-acetyl-4-deoxyneuraminic acid (9), by reaction with fowl plague virus sialidase. Further biochemical activities of 8 and 9 are reported.

Notes: The nN-1 ionization energies I1c and the gas-phase basicities GB of CH3-, Cl-, or CN-substituted quinuclidines have been measured by PE and ICR spectroscopy. The dependence of the shifts ΔI1c and ΔGB (relative to the values of the parent molecule) allow conclusions about the charge dispersal accompanying the nN-1 ionization or the protonation of quinuclidine in the gas phase. The agreement with the results of a minimal basis set ab initio calculation is excellent. Comparison of the solution pKa values with either I1c or GB reveals that 2-substituted quinuclidines exhibit sizeable solvent-induced proximity effects, i.e. that the corresponding quinuclidinium ions are more acidic in solution than expected on the basis of the gas-phase basicities. This agrees with earlier results concerning 2-substituted pyridines.

Notes: Macrocyclic Benzolactones by Ring Enlargement of 2-NitrocycloalkanonesReaction of 2-nitroalkanones with 1,4-benzoquinone in the presence of 1,8-diazabicyclo[5.4.0]undec-7-en gave (hydroxybenzo)nitrolactones of general formula 6 (Scheme 1). The transformation involves a Michael reaction, aromatization, and ring enlargement via a five-membered intermediate. The (hydroxybenzo)nitrolactones were converted to the already known (acetoxybenzo)oxolactones 15-17. The characteristic mass spectral behavior of the ring-enlarged products is discussed.

Notes: The 15N-NMR spectra of cis- and trans-2,3-dialkyl-substituted triaziridines are reported. The assignment of the 15N-NMR resonances is described, and the chemical-shift and coupling data are compared with those of aziridines and diaziridines. The 1J(N,H) coupling constants allow one to deduce the relative configuration of the involved N-atom. In CDCl3, a 1J(N,H) value of 58.1 ± 0.5 Hz is assigned to an N—H bond cis to two lone-pairs of electrons at neighboring N-atoms, i.e. to the cis,trans-triaziridinesThe first stereodescriptor denotes the relative configuration of the two equal alkyl substituents, the second the relative configuration of one alkyl substituent and the H-atom., and a value of 51.7 ± 0.5 Hz is assigned to a N—H bond cis to only one lone-pair of electrons, i.e. to trans, cis-triaziridines.

Notes: A Novel Ester Iridoid Glucoside from Sambucus ebulus L. (Caprifoliaceae)A novel ester iridoid glucoside, ebuloside (1,), which shows structure elements of the rare 7-Dehydrologanin derivatives combined with those of the Valerianaceae iridoids, was isolated from the roots of Sambucus ebulus L. Its structure was determined by MS, NMR, and CD spectroscopy as 7-oxo-8-deoxyvalerosidatum.

Notes: Reactions carried out on benzoyl (2) and hydroxybenzyl (10) derivatives of L-phenylalanine-cycloanhydride 1 lead to the conclusion that the structure 3, previously proposed for picroroccellin (a metabolite from the lichen Roccella fuciformis), should be revised to 6, While the FeCl3-catalyzed photo-oxidation of 1 gives 2, the N,N′-dimethyl derivative 7 leads to N,N′-dimethyl-2-benzylpiperazine-3,5,6-trione (9). N,N′ -diacetyl-L-phenylalanine-cycloanhydride 11 remains unchanged. It is established that N,N′ -substitutions of 2,5-dibenzylpiperazines-3,6-diones considerably influence their photo-oxidations under the reported conditions.

Notes: It is shown that 2-allylated anilines (cf. Schemes 2-4, 7, and 8) on irradiation in protic solvents such as H2O. MeOH, and EtOH in the presence of H2SO4 undergo a novel photosolvolysis reaction to yield specifically trans-2-hydroxy- and trans-2-alkoxy-1-methylindanes. Intermediates are presumably tricyclo[4.3.0.01,8]nona-2,4-dienes formed in an intramolecular [2s + 2s] cycloaddition reaction (cf. Scheme 7). On the other hand, N,N,N-trimethyl-2-(1′-methylallyl)anilinium salts 18 (Scheme 6) and 2-(3′-butenyl)-N,N-dimethylaniline (17) lose on irradiation in MeOH or H2SO4/MeOH the ammonium group reductively to yield (1-methylallyl)benzene (19) and 1-methylindane (20), respectively.

Notes: Polyacetylated 5,6,7,8-Tetrahydro-D- and L-neopterins. A Special Case of N(5)-Alkylation of 5,6,7,8-TetrahydroneopterinsImproved conditions are reported for the preparation of the earlier described (6R)- and (6S)-1′-O,2′-O,3′-O,2-N,5-pentaacetyl-5,6,7,8-tetrahydro-L-neopterins, one of which could be obtained as pure crystals. Its structure, determined by X-ray-diffraction analysis, corresponds to the (6R)-enantiomer. The method has also been used to make the corresponding D-diastereoisomers. Further acetylation of (6RS)-1′-O,2′-O,3′-O,2-N-tetraacetyl-5,6,7,8-tetrahydro-D-neopterin under drastic conditions yields a mixture of several polyacetylated D-neopterin derivatives and a polyacetylated ethyl-tetrahydro-D-neopterin which was isolated in crystalline form and established by X-ray-diffraction analysis to be (6R)-1′-O,2′-O,3′-O,4-O,2-N,2-N,8-heptaacetyl-5-ethyl-5,6,7,8-tetrahydro-D-neopterin.

Notes: The α-hydroxylation of chiral esters of 3-phenylpropionic acid by MoO5·Py·HMPT was optimized to 98% de and 73% yield by systematic variation of the reaction conditions. The addition of at least 3 equiv. of K(sec-BuO) proved to be essential.

Notes: The preparation and the CD spectra of optically pure (+)-trans-μ-[(1R,4S,5S,6R,7R,8S)-C,5,6,C -η : C,7,8,C-η-(5,6,7,8-tetramethylidene-2-bicyclo [2.2.2]octanone)]bis(tricarbonyliron) ((+)-7) and (+)-tricarbonyl[(1S,4S,5S,6R)-C-5,6,C-η-(5,6,7,8,-tetramethylidene-2-bicyclo[2.2.2]octanone)]iron ((+)-8), and of its 3-deuterated derivatives (+)-trans-μ-[(1R,3R,4S,5S,6R,7R,8S)-C,5,6,C-η : C,7,8,C-η-5,6,7,8-tetramethylidene(3-D)-2-bicyclo[2.2.2]-(octanone)]bis(tricarbonyliron) ((+)-11) and (+)-tricarbonyl[(1S,3R,4S,5S,6R)-C-5,6,C- η-(5,6,7,8-tetramethylidene(3-D)-2-bicyclo[2.2.2]octanone)]iron ((+)-12) are reported. The chirality in (+)-7 and (+)-8 is due to the Fe(CO)3 moieties uniquely. The signs of the Cotton effects observed for (+)-7 and (+)-8 obey the octant rule (ketone n→π*CO transition). Optically pure (-)-3R-5,6,7,8-tetramethylidene(3-D)-2-bicyclo[2.2.2]octanone ((-)-10) was prepared. Its CD spectrum showed an ‘anti-octant’ behaviour for the ketone n→π*CO transition of the deuterium substituent. The CD spectra of the alcoholic derivatives (-)-trans-μ-[(1R,2R,4S, 5S,6R,7R,8S)-C,5,6,C-η : C,7,8,C- η-(5,6,7,8-tetramethylidene-2-bicyclo[2.2.2]octanol)]bis(tricarbonyliron) ((-)-2) and (-)-tricarbonyl- [(1S,2R,4S,5S,6R)- C,5,6,C- η-(5,6,7,8-tetramethylidene-2-bicyclo[2.2.2]octanol)]iron ((-)-3) and of the 3-denterated derivatives (-)-5 and (-)-6 are also reported. The CD spectra of the complexes (-)-2, (-)-3, (+)-7, and (+)-8 were solvent and temperature dependent. The ‘endo’-configuration of the Fe(CO)3 moiety in (±)-8 was established by single-crystal X-ray diffraction.

Notes: The crystal and molecular structure of dinitrato(1,7,10,16-tetraoxa-4,13-diazacyclooctadecane)europium(III) nitrate, ([Eu(NO3)2(C12H26N2O4)]NO3) has been determined from single-crystal X- ray diffraction: a = 12.567(3), b = 11.585(3), c = 16.354(5) Å, β = 112.45(2)°, space group P21/n, Z = 4. The structure consists of discrete dinitrato complex cations and of nitrate anions. The Eu(III) ion is 10-coordinate, bonding to the six donor atoms of the macrocycle and to four O-atoms of the two bidentate nitrates. The mean distances are Eu—O(ether) = 2.60(2), Eu—O(NO3) = 2.47(3) and Eu—N = 2.62(2) Å. The metal site has an approximate C2 symmetry. The IR and Raman spectra show the presence of an ionic and of two bonded bidentate nitrates. These latter have a different v1-v4 splitting, which reflects their dissymmetrical bonding. Luminescence spectra have been recorded at 296, 77, and 4 K by laser-excitation techniques. One sharp 5D0←7F0 transition was observed and almost all the sublevels of the 7FJ manifold could be identified. The interaction between a sharp distribution of the phonon states (especially between 950 and 1200 cm-1) and the electronic 7F2 sublevels results in the presence of several satellite lines accompanying the 5D0→7F2 transition. In MeCN solutions, both luminescence and conductivity data point to the presence of the [Eu(NO3)2(2,2)]+ cation.

Notes: The Friedel-Crafts mono and double acylations of trans-μ-[(1RS,2RS,3SR,5RS,6SR,7SR)-C,2,3,C-η:C,6,7,C-η-(2,3,6,7-tetramethylidenebicyclo[3.2.1]octane)]bis(tricarbonyliron) (4) are highly stereoselective and yield trans-μ-{(1RS,2RS,3SR,5RS,6SR,7RS)-C,2,3,C-η :C,6,7,C-η-[(Z)-1-(3,6,7-trimethylidenebicyclo[3.2.1]-oct-2-ylidene)-2-propanone]}bis(tricarbonyliron) (5) and trans-μ-{(1RS,2RS,3SR,5RS,6SR,7SR)-C,2,3,C-η :C,6,7,C-η-[(Z,Z)-1,1′-(3,7-dimethylidenebicyclo [3.2.1] octane-2,6-diylidene)di(2-propanone)]}bis(tricarbonyliron) (6) whose structure has been established by single-crystal X-ray diffraction.

Notes: 14N- and 15N-NMR spectra have been recorded for 2-(aminomethyl)pyridine (1), tris[(2-pyridyl)methyl]amine (2), and some of their protonated forms. For 1, the most basic site is the aliphatic N-atom, whereas for 2 the pyridine N-atoms are more basic, in contrast to what might be expected for a tertiary aliphatic amine.

Notes: Synthesis of Triafulvene Precursors for Retro-Diels-Alder ReactionsTriafulvene precursors exo-15 and endo-15 have been prepared by addition of dibromocarbene to benzobarrelene 12 followed by a lithium-halogen exchange, methylation, and elimination of HBr (12→13→14→15), (Scheme 2). Gas-phase pyrolysis of exo/endo-mixtures of 15 above 400° gave minor amounts of naphthalene (16), traces of a hydrocarbon C4H4 identified by MS (presumably triafulvene 1) and predominantly (36%) the isomerization product 17 (Scheme 3). In a second synthetic approach the well-known cycloheptatriene-norcaradiene equilibrium of type 26⇆27 has been utilised to prepare various endo-trans-3-(X-methyl) tricyclo[3.2.2.02,4]nona-6,8-dienes 31 (Scheme 5). However, numerous elimination experiments 31→9 failed so far. The structure of two rearrangement products 33 and 34 (Scheme 6) has been elucidated.

Notes: Optically pure (-)-trans-μ-[(1R,2R,3S,4S,5S,6R)-C,2,3,C-η:C,5,6,C-η-(2,3,5,6,7-pentamethylidenebicyclo[2.2.2]octane)]bis(tricarbonyliron) ((-)-9), (-)-trans-μ-[(1R,2R,3S,4S,5S,6R,7S)-C,2,3,C-η:C,5,6,C-η-(7-methyl-2,3,5,6-tetramethylidenebicyclo[2.2.2]octane)]bis(tricarbonyliron) ((-)-10), and (-)-trans-μ-[(1R,2R,3S,4S,5S,6R,7R)-C,2,3,C-η:C,5,6,C-η-(2,3,5,6-tetramethylidene(7D)bicyclo[2.2.2]octane)]bis(tricarbonyliron) ((-)-16) have been prepared. Their CD spectra were solvent- and concentration-independent, but temperature-dependent, in accord with the existence of equilibria between rapidly interconverting diastereoisomeric species which can be interpreted as arising from distortions of the tricarbonyl(diene)iron units from the Cs symmetry.

Notes: Optically Active 4,5-Epoxy-4,5-dihydro-α-ionones; Synthesis of the Stereoisomeric 4,5:4′,5′-Diepoxy-4,5,4′,5′-tetrahydro-∊,∊-carotenes and the Steric Course of their HydrolysisWe prove that epoxidation with peracid of α-ionone, contrary to a recently published statement, predominantly leads to the cis-epoxide. Acid hydrolysis affords a single 4,5-glycol whose structure, established by an X-ray analysis, shows that oxirane opening occurred with inversion at the least substituted position (C(4)). Stable cis-and trans-epoxides are prepared by epoxidation of the C15-phosphonates derived from α-ionone. Both the racemic and optically active form are used for the synthesis of the 4,5:4′,5′-diepoxy-4,5,4′,5′-tetrahydro-∊,∊-carotenes having the following configuration in the end groups: meso-cis/cis, meso-trans/trans, rac-cis/trans, rac- and (6R, 6′ R)-cis/cis, rac- and (6R, 6′R)-trans/trans, rac- and (6R, 6′R)-cis/trans, and (6R, 6′ R)-cis/∊. Acid hydrolysis of the cis/cis-epoxycarotenoids under relatively strong conditions occurs again with inversion at C(4)/C(4′) in case of the cis/cis-epoxycarotenoids, but at C(5)/C(5′) in case of the trans/trans-epoxycarotenoids. An independent synthesis of this 4,5,4′,5′-tetrahydro-∊,∊-carotene-4,5,4′,5′-tetrol is presented. The irregular results of the oxirane hydrolysis are explained by assumption of neighbouring effects of the lateral chain. 400-Mz-1H-NMR data are given for each of the stereoisomeric sets. In the visible range of the CD spectra, the (6R, 6R′)-epoxycarotenoids compared with (6R, 6R′)-∊,∊-carotene exhibit an inversion of the Cotton effects.

Notes: The polymer-bound heptapeptide H-Glu-His-Pro-Gly-Ser-Gly-PEGM was designed as a ‘single-centre model’ for the active site of α-chymotrypsin. The peptide was synthesized according to the general principles of the liquid-phase method for peptide synthesis, and its conformational properties were investigated by CD and IR spectroscopy in solution and in the solid state. In harmony with empirical prediction codes, experimental and theoretical conformational considerations, the peptide adopts a β-turn conformation stabilized by H-bonds involving the side chains of Glu, His, and Ser. The development of a H-bonded system similar to the active site of α-chymotrypsin leads to implications with respect to a possible catalytic activity of the model peptide.

Notes: A novel, mild, and highly stereoselective transformation of epoxides to azidohydrins by treatment with Et3Al/HN3 in toluene is described. As an example for the versatility of the reaction, a polyfunctional compound, 14,15-epoxy-14,15-dihydromilbemycin D (1), was transformed to 14-azido-14,15-dihydro-15-hydroxymilbemycin D (2) in 61% yield.

Notes: Biphenylene dianion has been prepared by Li reduction of the parent hydrocarbon. It is stable below -30° and was characterized by its 1H- and 13C-NMR spectra. A comparison of these data with those of the dication indicates the existence of ion pairs in the dianion case which are responsible for a different charge distribution. The diamagnetic ring currents of both ions, however, are of comparable magnitude, and both are more diatropic than the parent hydrocarbon. Predictions of the π-charge-density effect on 1H chemical shifts are improved by calculations that use the linear and quadratic electric-field effect equation instead of the simple Spiesecke-Schneider relation.

Notes: A general procedure for the design of synthetic vaccines with the retained conformational features of protein antigenic determinants is described. This new concept emerges from detailed studies on the relationship between primary sequence and secondary structure formation of synthetic peptides and takes advantage of the amphiphilic nature of epitope-containing peptide segments in the native protein to accomplish structural modifications. These segments, for example amphiphilic helices or β-sheets, are stabilized by the insertion of secondary structure-inducing amino-acid residues on the hydrophobic part of the peptide without affecting the spatial arrangement of functional residues on the hydrophilic side. The availability of amphiphilic peptides with tailor-made conformational properties, e.g. helices, β-sheets, and, moreover, assemblies of these blocks to structures of higher order (‘folding units’), allows the presentation and stabilization of continuous as well as discontinuous epitopes by this approach. This strategy is exemplified for the case of two discontinuous epitopes taken from lysozyme, which are matched to host molecules with adequate conformational features by the help of computer-assisted molecular modelling. The implications of this new concept for the design of synthetic vaccines are discussed with special emphasis to the important role of peptide synthesis and chemical structure modification.

Notes: 2-Aza-1,3-dienes. Synthesis and Properties of 1-Alkylpyrazone-imines and their TautomersTreatment of 5-dialkylamino-1,1-dicyano-2-aza-1,3-dienes (or their 1-methoxycarbonyl analogoues) with primary amines gives substituted 1-alkyl-3-cyano-(or methoxycarbonyl-)pyrazoneimines. Tautomeric behaviour, nucleophilic addition to imino function and spectroscopic data of these isomers are examined.

Notes: The title compound 1, {[Fe(H2pztc)(H2O)2] · 2 H2O}∞, has been prepared from pyrazinetetracarboxylic acid (H4pztc) and Fe(II) salt in H2O. It crystallizes in the monoclinic space group P21/a with cell parameters a = 13.56(1) Å, b = 7.17(1) Å, c = 6.48(1) Å, β = 101.0(2)°, V = 618.4 Å3. The molecules form infinite parallel chains with bis(bidentate) coordination (through N and O) of the bridging pyrazine ligands. Two trans-COOH groups of the ligand remain uncoordinated, and two trans-H2O ligands complete a pseudo-octahedral Fe(II) coordination which is distorted by the steric effect of the free COOH groups. The parallel polynuclear chains are linked through an extended network of H-bonds involving the COO functions of the bridging ligand and the coordinated and lattice H2O molecules. Mössbauer and magnetic-susceptibility data suggest normal paramagnetic behaviour of high-spin Fe2+. An observed drop below 15 K in effective magnetic moment for 1 was attributed to temperature-dependent population changes of the levels of the ground state 5Γ, and not to antiferromagnetic coupling (J 〈 1 cm-1). This result establishes that the obvious potential magnetic exchange pathway through the pyrazine bridges is inefficient, and this may be attributed, in part, to the high planarity of Fe(H2pztc) moieties.

Notes: Results of voltammetric, potentiometric, chronoamperometric, ion transport, and extraction studies on neutral carrier based, plasticized poly(vinyl chloride) membranes are summarized. They unambiguously confirm that such bulk membranes dispose of immobile anionic sites. These fixed sites lead to a Donnan exclusion of other anions from the membrane and thus to a permselectivity for cations. The results are in perfect agreement with the predictions of earlier membrane models. A rigorous Poisson-Boltzmann analysis of macroscopic liquid membranes clearly indicates that space-charge at the membrane/solution interfaces does not influence the electrochemical properties and the ion-selectivity behavior at steady state.

Notes: Peptide-Bond Formation with C-Terminal α,α-Disubstituted α - Amino Acids via Intermediate Oxazol-5(4H)-onesThe formation of peptide bonds between dipeptides 4 containing a C-terminalα,α-disubstituted α-amino acid and ethyl p-aminobenzoate (5) using DCC as coupling reagent proceeds via 4,4-disubstituted oxazol-5(4H)-ones 7 as intermediates (Scheme 3). The reaction yielding tripeptides 6 (Table 2) is catalyzed efficiently by camphor-10-sulfonic acid (Table 1). The main problem of this coupling reaction is the epimerization of the nonterminal amino acid in 4 via a mechanism shown in Scheme 1. CSA catalysis at 0° suppresses completely this troublesome side reaction. For the coupling of Z-Val-Aib-OH (11) and Fmoc-Pro-Aib-OH (14) with H-Gly-OBu1 (12) and H-Ala-Aib-NMe2 (15), respectively, the best results have been obtained using DCC in the presence of ZnCl2 (Table 3).

Notes: (1RS, 5SR)-2,2,5-Trimethylcyclopentane-1-carboxylic acid (17) and (1r, 2RS, 5SR)-1,2,5-trimethylcyclopentane-1-carboxylic acid (19) are the starting materials for the α-alkynone routes to (±)-capnellene and for similar efforts towards ptychanolide. Since 17 and 19 have, so far, been available only by a branching reaction from the same precursor, the cyanohydrin mixture 2/3, a modified synthesis for 17 and a new one for 19 was developed (Scheme 1). The common precursor 2/3 was treated with POCl3 which effected normal dehydration to 6 (47%, major path) in competition with Me migration to 8 and 9 (17%). The minor path to 8 and 9 could be reduced to 3% when SOCl2 was used for the dehydration of 2/3. This reaction was the basis for an improved synthesis of 17 from 1, using the steps b, e, i, r, and v see Scheme 1 in an overall yield of 35%. The POCl3 reaction was also studied with the pure cyanohydrins 2 and 3, the configurations of which were determined by an X-ray analysis of 2. Me migration did not occur form 2 but only from 3 (25%), which has HO—C(1) and H—C(5) in a cis position. With SOCl2, 3 underwent only 5% Me migration. The new synthesis of 19 started with 4 using the steps h, n, p, and s (see Scheme 1) in an overall yield of 68%.

Notes: A synthesis of N-acetylneuraminic acid (1) and of N-acetyl-4-epineuraminic acid (2, R = H) from 2-acetamido-4,6-O-benzylidene-1,2-dideoxy-1-nitro-D-mannopyranose (3) and 2-acetamido-1,2-dideoxy-4,6-O-isopropylidene-1-nitro-D-mannopyranose (4), respectively, is described. Michael addition of 3 and 4 to tert-butyl 2-(bromomethyl)prop-2-enoate (5) and subsequent hydrolytic removal of the NO2 group gave the 4-nonulosonate tautomers 6/7 and 8/9, respectively (Scheme). Stereoselective reduction of 6/7 and 8/9 with NaBH4/AcOH in dioxane/H2O yielded 12/13 (94:6) and 14/15 (92:8), respectively. Reduction of 6/7 and 8/9 in the absence of AcOH or in EtOH gave 12/13 (15:85) and 14/15 (15:85), respectively. Ozonolysis of 12 and 13 followed by hydrolysis gave tert-butyl neuraminate 22 and tert-butyl 4-epineuraminate 24, respectively. Ozonolysis of 14/15, separation of the products 20 and 21, and hydrolytic removal of the isopropylidene groups gave 22 and 24, respectively. The tert-butyl ester 22 was saponified to give 1, which was further characterized as the methyl ester 23. Saponification of 24 gave the crude 4-epimer of 1, which was converted into the stable Na salt 2 and also into the methyl ester 25.

Notes: Preparation of Unprotected and Partially Protected 1-Deoxy-1-nitro-D-aldoses and Some Representative X-Ray Structure AnalysesThe unprotected and partially protected 1-deoxy-1-nitro derivatives of α-and β-D-glucopyranose (see 15 and 14), β-D-mannopyranose (see 16), N-acetyl-β-D-glucosamine (see 17), β-D-galactofuranose (see 19), β-D-ribofuranose (see 20), α-D-arabinofuranose (see 21), 4,6-O-benzylidene-β-D-glucose (see 40), N-acetyl-4,6-O-benzylidene-β-D-glucosamine (see 41), and 4,6-O-benzylidene-β-D-galactose (see 42) were prepared by ozonolysis of the corresponding nitrones which were obtained from the acid-catalyzed reaction of p-nitrobenzaldehyde with the hydroxylamine 4, the unprotected oximes 3 and 5-9 and the 4,6-O-benzylidene oximes 35-37, respectively (Schemes 1-3). The gluco- and manno-nitrones 10 and 12 were isolated, and their ring size and their anomeric and (E/Z) configurations were determined by NMR spectroscopy and by their transformation into their corresponding nitro derivatives. The structure of the deoxynitroaldoses were determined by NMR spectroscopy, polarimetry, and, in the case of 14, 16, and 17, by formation of the 4,6-O-benzylidene (14→40) or 4,6-O-isopropylidene (16→43, 17→23) derivatives (Scheme 3). Acetylation of the nitroglucopyranose 14, the 2-acetamido-nitroglucopyranose 17, and the nitrogalactofuranose 19 gave the crystalline peracetylated nitroaldoses 22, 24, and 45, respectively (Scheme 4, Figs. 1 and 3); acetylation of the nitromannopyranose 16 gave the nitro-arabino-glycal 44 (Scheme 4). The structure of the peracetylated nitroglucopyranose 22, the nitroglucosamine 25, the nitrogalactofuranose 45, and the nitroribofuranose 20 were confirmed by X-ray analysis (Figs. 1 4). In all cases, including the β-D-glucopyranose derivative 22, considerably shortening of the (endocyclic) C(1)-O bond was observed. Base-catalyzed anomerization of the β-D-configurated nitroglucopyranose 14, the nitromannopyranose 16, the benzylidene acetal 40 of nitroglucose, and the 2,3,4,6-tetraacetylated glucosamine derivative 24 gave the corresponding nitro-α-D-aldoses 15, 26, 47, and 25, respectively (Scheme 4).

Notes: Regioselective Functionalisation of N,N-Diethyl-1,6-methano[10]annulene-2-carboxamidesLithiation of N,N-diethyl-1,6-methano[10]annulene-2-carboxamide with BuLi followed by quenching with different electrophiles yields 2,10-disubstituted-1,6-methano[10]annulenes.

Notes: Synthesis, Reactions, and Photochemistry of Heterocyclic N-AlkylthioamidesVarious heterocyclic N-alkylthioamides of the pteridine (2, 7) and pyridine series (13) have been synthesized and investigated regarding their photooxidation. The compounds are very photolabil under aerobic conditions and are converted into the corresponding amides (1, 6 and 12, resp.) on irradiation.

Notes: Changes in chemical shifts of olefinic protons in a number of α,β- and α,β,γ,δ-unsaturated carboxylic acids caused by ionization of the COOH group were investigated. The ionization shifts of α-H-atoms are -0.09 to 0.07 ppm, those of β-H-atoms are 0.32-0.47 ppm. The ionization shifts of δ-H-atoms are substantially larger than those of γ-H-atoms. The ionization shifts can be used for immediate determination of the esterification site in monoesters of (2E,4Z)-2,4-hexadienedioic (muconic) acid, which are of interest in connection with synthetic studies on verrucarins. Thus, isomerization by heating in aqueous solution of monoesters of (2Z,4Z)-2,4-hexadienedioic acid yields 1-monoesters rather than 6-monoesters of (2E,4Z)-2,4-hexadienedioic acid, in accordance with the isomerization mechanism involving anchimeric assistance of the free COOH group. Solutions of the ABXY spectra of olefinic protons of monomethyl (2E,4E)- and (2Z,4Z)-2,4-hexadienedioate are reported.

Notes: A highly regio- and stereoselective Diels-Alder reaction between dienophiles of type I and dienes of type II (Scheme 1) gives rise to Diels-Alder adducts of type III. Upon treatment with BF3.Et2O, these adducts are smoothly converted into the corresponding enones (Scheme 6). Under mild acidic conditions, enone (±)-33 gave bicyclic diketone (±)-34 via an intramolecular Michael-type addition. Diketone (±)-34 has the correct relative configuration and a suitable ketone function at C(6) for further conversion into the hexahydrobenzofuran portion of the avermectins and milbemycins.

Notes: The syntheses of 2,3-dimethylidene- and 2,3,5,6-tetramethylidene-7-oxabicyclo[2.2.1]heptanes substituted in position C(1) are reported. The 1-dimethoxymethyl group in derivatives 2 and 6 controls the regioselectivity of the Lewis-acid-catalyzed Diels-Alder additions with methyl vinyl ketone and butynone. For the EtAlCl2-catalyzed addition of methyl vinyl ketone to 6, the regioselectivity can be reversed by a small solvent modification. The tetraene 2 is a versatile reagent for regioselective ‘tandem’ cycloadditions.

Notes: Two-dimensional, high-field NMR methods are employed in confirming the relative configuration at the C(20) ethyl side-chain junction as S* in the natural alkaloid tubotaiwine (dihydrocondylocarpine).

Notes: A New Synthesis of (±)-DihydrorecifeiolideEthyl 1-(2′-formylethyl)-2-oxocyclooctane-1-carboxylate (2) prepared by Michael reaction of ethyl 2-oxocyclooctane-1-carboxylate (1) was regioselectively methylated at the aldehyde group with (CH3)2Ti[OCH(CH3)2]2 to give 3 (Scheme 1). The alcohol 3 was treated with Bu4NF to give the deethoxycarbonylated product 4 which by distillation gave the bicyclic enol ether 5. Oxidation (m-chloroperbenzoic acid) of 5 and reduction of the resulting oxolacton 6 yielded the title compound (±)-dihydrorecifeiolide (7) in an overall yield of nearly 50 %. Methylation of the aldehyde 2 with MeLi gave the ring-enlarged lacton 9 in poor yield (13 %). The deethoxycarbonylation reaction 3 → 4 was studied in more detail (Scheme 3).

Notes: Metabolites of Microorganisms. Sulfur-Containing Ansa Compounds of the Naphthomycin TypeFrom a strain of Streptomyces (Tü 2357) in addition to naphthomycin A, 4 new yellow pigments were isolated and their structures determined by spectroscopic comparison with naphthomycin A. Whereas the naphthomycins D and E are simple derivatives of naphthomycin A, having OH and H, respectively, instead of Cl, the naphthomycins F and G contain an N-acetylcysteine residue linked to the aromatic moiety by a thioether group. Degradations with O3 yielded identical products from the naphthomycins A, D, F, and G, showing coincident configurations in parts of the molecules. Naphthomycin F shows some biological activity against gram-positive bacteria and fungi, although much weaker than naphthomycin A. The naphthomycins D, E, and G are inactive against microorganisms.

Notes: The crystal structure of (±)-corynoline (1) has been determined by X-ray diffraction methods. The rings B and C form the half-chair and the twist-half-chair conformations, respectively. The B/C ring conjunction exists in an anti-cis conformation, with a N … H—O intramolecular H-bond. Conformational energy calculation by the CNDO/2 method show that the conformations of 1, (+)-chelidonine (2), and their acetates, observed in crystal structures, are all in the one of total energy minimum.

Notes: (2S,4S)-2-(tert-Butyl)-5-oxo-1,3-dioxolan-4-acetic acid (1) was dilithiated to the enolate 2 in toluene and THF with lithium diisopropylamide (LiN(i-Pr)2) under various conditions. Deuteration experiments with 2 showed that two different stable forms of the enolate could be produced, depending on whether the deprotonation of 1 had been carried out in toluene or THF. The generated (i-Pr)2NH was coordinated to the enolate and, hence, served as a strong lipophilic solvating agent. LiN(i-Pr)2 could substitute the amine ligands of the two species to a different extent. THF was partially able to displace (i-Pr)2NH that solvated the species produced in toluene, but the coordination of the amine to the one produced in THF was quantitive. Correlations with given explanations are made.

Notes: The synthesis of a mononuclear Rh(III) complex, as a representative example of a series of related species, containing two cyclometallating ligands ppy (2-phenylpyridine) and one diimine bpy (2,2′-bipyridine) from a binuclear Cl-bridged compound is described. The absorption spectrum shows a maximum at 364 nm (ε = 7000), with a very weak shoulder (ε = 10) at 454 nm. This band is tentatively assigned to a metal-to-ligand charge-transfer transition. A reversible, one-electron reduction appears in the cyclic voltammogram at E1/2 = -1.41 V (vs. NHE) and a irreversible oxydation at Ep = + 1.1 V. A detailed NMR analysis including 13C-NMR, NOE, SFORD as well as deuteration of the bpy ligand indicates the formation of only one isomer, having a C2 axis, bisecting the bpy ligand, with the two carbon ligands in cis-position. 103Rh, 13C and 103Rh,H couplings are observed.

Notes: Synthesis and Reactivity of Lumazine-7-sulfenic AcidsThe chemical synthesis of the pteridine-7-sulfenic acids 13-16 is described (Scheme 1). The 1,2,3,4-tetrahydro-1,3,6-trimethyl-2,4-dioxopteridine-7-sulfenic acid (14) was isolated as a stable crystalline solid. Its chemical reactivity was investigated and the physical properties determined. In the solid state, the S-oxide form 14A predominates, but in protic solvents the S-OH tautomer 14 exists most likely. In basic medium, the pteridine-7-sulfenate species is stable, whereas a low pH gives rise to a disproportionation to the disulfide 10 and the corresponding pteridine-7-sulfinic acid 37 (Scheme 4). Reaction of 14 with ethyl propiolate leads, under cis-addition, to 36, oxidation with KMnO4 forms 1,2,3,4-tetrahydro-1,3,6-trimethyl-2,4-dioxopteridine-7-sulfonic acid (38) and NaBH4 reduction the corresponding 7-mercaptopteridine dione 18 (Scheme 4).

Notes: CO and H2 are photogenerated simultaneously by visible-light irradiation of systems containing a photosensitizer, the [Ru(bpy)3]2+ complex, Co(II) species as homogeneous catalysts, which mediate CO2 and H2O reduction by intermediate formation of Co(I), a tertiary amine as electron donor, which provides the electrons for the reduction, and an organic solvent which also facilitates dissolution of CO2. The efficiency of (CO + H2) gas production and the selectivity CO/H2 markedly depend upon the composition of the medium, the nature of the tertiary amine, the solvent, and the ligand of the Co ions. 2,9-Dimethyl-1,10-phenanthroline is particularly effective in promoting CO and H2 formation, giving a quantum yield of 7.7% in (CO + H2) (1.2% for CO and 6.5% for H2). The process consists of two catalytic cycles: a photocatalytic cycle for the Ru complex and a double dark reaction pathway for the Co species; oxidative and/or reductive quenching of the excited state of the photosensitizer lead to the formation of Co(I) species which reduce either CO2 or H2O to CO or H2, respectively.

Notes: Estimation of preferred conformation, orientation, and accumulation of adrenocorticotropin (1-24)-peptide at an aqueous-hydrophobic interface produced a model that agreed with that developed from experimental observations with lipid membranes. Thus, the N-terminal message segment (residues 1-11) was incorporated into the hydrophobic phase as an α-helical, perpendicularly oriented domain with an apparent dissociation constant of ca. 5 · 10-5 M. The C-terminal address segment (residues 12-24) remained in the aqueous phase as a random-coil domain. Three parameters proved sufficient to define the model: the Gibbs free energy of hydrophobic association, the molecular amphiphilic moment, and the molecular electric dipole moment. For estimating interactions with biologic membranes (that carry a net negative charge), the Boltzmann distribution of charged peptides was also considered. The estimations were extended to adrenocorticotropin (1-10)-peptide and α-melanotropin. In the first case, the prediction agreed with the earlier observations, in the second, it awaits its experimental proof. The estimated membrane structures were compared with available biologic data. As for opioid peptides, it appears that the amphiphilic moment is an important new parameter for determining quantitative structure-activity relationships (QSAR) in receptor selection and biologic potency.

Notes: The syntheses of 2,3,5-trimethylidenebicyclo[2.2.1]heptane (1) and 2,3,5,6,7-pentamethylidenebicyclo[2.2.2]-octane (2) are reported. The Diels-Alder additions of the diene moieties of these polyenes can be regioselective, probably because of a possible transannular interaction between the homoconjugated methylidene and s-cis-buta-diene groups.

Notes: The N(1)- and N(2)-(2′-deoxyribofuranosides) 1 and 2, respectively, of 8-aza-7-deazaguanine were prepared via phase-transfer glycosylation in the presence or absence of Bu4NHSO4 as catalyst of 6-amino-4-methoxy-lH-pyrazolo[3,4-d]pyrimidine (7c) with 2-deoxy-3,5-di-O-(p-toluoyl)-α-D-erythro-pentofuranosyl chloride (10). On a similar route, but without catalyst and employing THF as organic phase, the 6-amino-4-chloronucleosides 11b and 12b were synthesized from 7a and converted into the N(1)-and N(2)-substituted 4-thioxo analogues 17a and 18a, respectively. The ratio of N(1)- to N(2)-glycosylation was 2:1 for 7c and 1:1 for 7a, viz. depending on the nucleobase structure. The rate of the H+-catalyzed N-glycosyl hydrolysis was strongly decreased for the N(2)-(β-D-2′-deoxyribofuranosides) as compared to the N(1)-compounds. However, the N(1)-nucleoside 1, which is an isostere of 2′-deoxyguanosine, is sufficiently stable to be employed later in solid-phase oligonucleotide synthesis.

Notes: Synthesis of Betenamine and of Betalaine Model SubstancesFor comparisons of color, spectroscopic properties, pKa values, and stabilities, a number of model substances containing the 1,7-diazaheptamethinium chromophore 8 of the yellow and red betalaine plant pigments were prepared by the thermal or photolytic ring opening of simple pyridine derivatives (such as 2 and 14-16), followed by the introduction of amines. Among the novel compounds prepared were betenamine perchlorate (5), the ‘naked’ ring system of the beet-pigment betanine (C) as well as two 1,7-diazaheptamethinium salts 25 and 27 with terminal amono acids. The synthesis of 5 started with 4-(2-aminoethyl)pyridine (1) and proceeded via 2, ring opening with indoline to 4, saponification, and intramolecular amine replacement (Scheme 1). The syntheses of 25 and 27 involved only one step, namely ring opening of γ-picoline using (S)-cyclodopa (24) and (S)-proline (26), respectively (Scheme 3).

Notes: Synthesis of Pentafulvalene by Oxidative Coupling of Cyclopentadienide with Copper(II) ChlorideStarting with a nearly quantitative coupling of cyclononatetraenide 7 to 1, 1′-dihydrononafulvalene 8 by means of AgBF4, a simple general synthetic concept for fulvalenes is outlined (Scheme 2), consisting in an oxidative coupling of ‘Hückel anions’ like 2 and 7 to 1, 1′-dihydrofulvalenes 10 with Ag(I) or Cu(II) salts, followed by deprotonation (→11) and oxidation (→12); it has been realised in the case of pentafulvalene (1; overall yield 61%; Scheme 3) and 1,2:5,6-dibenzopentafulvalene (18; overall yield 66%, Scheme 4). NMR-spectroscopic investigations show that 1 is a non-aromatic compound with strongly alternating bond-lengths, its π-system being even more localised than that of simple pentafulvenes. In fact, 1 is extremely reactive in concentrated solutions above -50°. Besides of polymerisations, Diels-Alder dimerisation 1→19 followed by a rearrangement 19→20 takes place (Scheme 5).

Notes: Ab initio calculations of structure, properties, and tautomerization reactions of triazene (1) at the HF/3-21G//3-21G, HF/6-31G*//6-31G*, HF/6-31G**//6-31G*, and MP2/6-31G*//6-31G* levels led to the following conclusions and predictions: (a) Calculations of the ground-state structure of (E)- and (Z)-triazene (1a and 1b, respectively) at various levels of theory show for both isomers C1 geometry with a rather flat pyramidal configuration at N(3), and small energy differences (0.2-7.2 kJ/mol) between C1 and Cs geometry, i.e. inversion at N(3) is a quasi-free process. With all levels of calculations, 1a is found to be of lower energy than 1b by 23-30 kJ/mol. (b) Comparison of vibrational frequencies of (E)-diazene (3) calculated at the HF/3-21G level with experimental values reveals that HF/3-21G calculations are reliable for the prediction of vibrational frequencies of polyaza compounds, if corrected by a factor of 0.91. On this basis, the harmonic vibrational frequencies of 1a and 1b were predicted. (c) For the rotation around the N(2) - N(3) bond of 1a two conceivable transition states, 5a (syn) and 5b (anti) were located (HF/3-21G). The energy differences between 5a or 5b, and 1a are in the order of magnitude of 50-56kJ/mol and show a slight preference for the anti-mode, i.e. energy barriers for the N(2) - N(3) rotation are obtained comparable to those observed experimentally with substituted (E)-triazenes (4). (d) Protonation of 1a at N(1), N(2), or N(3) leads to 6a, 6b, and 6c, respectively -the last one resembling an intermediate of formation of 1 from hydrogendiazonium ion (7) and ammonia (8). Energetically, the conjugate acids of 1a follow the sequence 6a 〈 6c 〈 6b. (e) The preference of N(1) protonation of 1a is also reflected in the relatively high gain of energy in the formation of H-bonded dimers of 1a with H-bonds from N(3) - H to N(1). Calculations of three different H-bonded dimers 9a-c of 1a with the 3-21G basis show that an eight-membered cyclic dimer 9c with two H-bonds from N(3)—H to N(1) is energetically most favoured (67.5 kJ/mol below two separate molecules of 1a). This dimer might well be the starting situation of double intermolecular H-transfer leading to an automeric dimer 9c via an energetically low-lying transition state 12, thus offering a low-energy pathway for the known easy tautomerization of mono- or disubstituted (E)-triazenes. For 9c⇄9c, the activation energy including correction for polarization and correlation effects as well as for vibration zero-point energy is estimated to be ca. 54kJ/mol. (f) A six-membered cyclic dimer 9b of 1a with two H-bonds from N(3)—H to N(2) might be involved for double H-transfer via a transition state 11 to a dimer 10 of (E, Z)-azimine (2). This process, however, turns out to be energetically highly disfavoured (estimated energy barrier for 9b→10: 232 kJ/mol) in contrast to the reverse reaction (10→9b via 11: 4 kJ/mol). This leads to the prediction that azimines bearing an H-atom at N(2) might be kinetically too instable for isolation, being, instead, easily tautomerized to triazenes by bimolecular H-transfer.

Notes: On the Photochemistry of (Z,Z)-2,7-Cyclodecadien-1-one and 4,8-Cyclododecadien-1-one. Synthesis and Properties of Tricyclo[5.3.0.02,8]decane SystemsIrradiation of (Z,Z)-2,7-cyclodecadien-1-one (3) yields (Z,Z)-3,7-cyclodecadien-1-one (12) or tricyclo-[5.3.0.02,8]decan-4-one (16), depending on the reaction conditions. Irradiation of 4,8-cyclododecadien-1-one (28) results also in a light-induced transannular [2 + 2] cycloaddition, yielding tetracyclo[7.3.0.02,1003,6]dodecan-1-one (30). Starting from 16, the preparation of tricyclo[5.3.0.02,8]dec-4-ene (19), tricyclo[5.3.0.02,8]dec-4-ene (21) and tricyclo[5.3.0.02,8]deca-3,5-diene (24) is described. The 1H-NMR and 13C—NMR spectra of the newly prepared compounds are discussed. In the case of 19, 21, and 24, the electronic structure is discussed on hand of their PE spectra.

Notes: 1,3-Butadienyl Thiocyanates in the Diels-Alder Reaction Followed by a [3,3]-Sigmatropic Shift(E)- and (Z)-1,3-Butadienyl thiocyanates 3, 4, and 12-15 have been synthesized selectively. Their use as dienes for Diels-Alder reactions followed by a [3,3]-sigmatropic shift to obtain an isomeric isothiocyanate has been studied. The butadienyl thiocyanates are, unfortunately, not very reactive in Diels-Alder reactions. This disadvantage can be overcome, if a trapping reaction with EtOH is added to the two-step sequence. This sequence allows to get good yields of the O-ethyl thiocarbamates 18-23, even if the first two reactions have not favorable equilibrium constants.

Notes: (S,S)-N,N′ -Bis(aminoacyl)ethane- and (S,S)-N,N′ -bis(aminoacyl)propanediamines (AA-NN-2 and AA-NN-3, respectively, AA = alanine, phenylalanine, valine) were synthesized as the dihydrochlorides, and their complexes with Cu(II) studied potentiometrically. Since these ligands in the presence of Cu(II) are able to perform chiral resolution of D,L-dansylamino acids in HPLC (reversed phase), in a certain pH range (6.5-8.5), it is important to know the equilibria existing between ligands and copper in aqueous solution. For AA-NN-2, four species, CuLH3+, CuL2+, Cu2L2H-22+, and CuLH-2, were detected, whereas for AA-NN-3, only CuLH3+, CuL2+, and CuLH-2 were found. The aim is to find out which complexes may be involved in the recognition process.

Notes: The synthesis of 4-methylumbelliferyl α-D-glycoside 13 of N-acetyl-4-deoxyneuraminic acid and its behaviour towards bacterial sialidases is described. N-Acetyl-4-deoxyneuraminic acid (1) was transformed into its methyl ester 2 and then acetylated to give the anomeric pentaacetates 3 and 4 of methyl 4-deoxyneuraminate and the enolacetate 5 (Scheme). A mixture 3/4 was treated with HCl/AcCl to give the glycosyl chloride, which was directly converted into the 4-methylumbelliferyl α-D-glycoside 9 of methyl 7-O,8-O,9-O,N-tetraacetylneuraminate and into the 2,3-dehydrosialic acid 11. The ketoside 9 was de-O-acetylated to 12 with NaOMe in MeOH. Saponification (NaOH) of the methyl ester 12 followed by acidification gave the free 13, which was also converted into the sodium salt 14 by passage through Dowex 50 (Na+). The 4-deoxy α-D-glycoside 13 is not hydrolyzed at significant rates by Vibrio cholerae and Arthrobacter ureafaciens sialidase. Neither the free N-acetyl-4-deoxyneuraminic acid (1), nor the α-D-glycoside 13 inhibit the activity of these sialidases.

Notes: Succesive treatment of chiral esters 1 with LiN(i-Pr)2/Me3SiCl and di(tert-butyl) azodicarboxylate/TiCl4/Ti(i-PrO)4 gave N,N′ -di[(tert-butoxy)carbonyl]hydrazino esters 9 which on deacylation, hydrogenolysis, transesterification, and acidic hydrolysis furnished (2S)-α-amino acids 6 in high enantiomeric purity with efficient recovery of the auxiliary alcohol 7.

Notes: The hydroxylation of geraniol (8) by cytochrome P-450 (P-450Cath.) from the subtropical plant Catharanthus roseus (L.) G. DON was optimised to give 8-hydroxygeraniol (9) as the single product in 35% yield. Incubations of different 13C- and 2H-labelled geraniols revealed that H-abstraction is completely regioselective in favour of the CH3 group trans to the chain at C(6) of 8. An intramolecular isotope effect kH/kD = 8.0 was determined, suggesting that H-abstraction is one of the major rate-contributing steps; however, the intermolecular isotope effect was surprisingly inverse at low conversion kH/kD = 0.50, indicating the existence of rate-contributing steps preceding the first irreversible, isotope-sensitive reaction in the sequence.

Notes: Nitrocyclohexene undergoes facile SnCl4-induced, [4 + 2]-cycloadditions with simple cycloalkenes to produce nitronates. The nitronates can be transformed sterospecifically into a number of other functional groups (alcohol, ketone, oxime, amine) by hydrolytic, reductive, and oxidative processes. The mechanism of the [4 + 2]-cycloaddition is believed to involve formation of a zwitterionic intermediate which can collapse via competing pathways to form the observed products. 1,3-Dipolar cycloadditions of the nitronates are described.

Notes: It is shown that (-)-(S)-N,N-dimethyl-2-(1′-methylallyl)aniline ((-)-(S)-4), on direct irradiation in MeCN at 20°, undergoes in its lowest-lying triplet state an aromatic di-π-methane (ADPM) rearrangement to yield (-)-(1′R,2′R)- and (+)-(1′R,2′S)-N,N-dimethyl-2-(2-methylcyclopropyl)aniline ((-)-trans- and (+)-cis-7) in an initial trans/cis ratio of 4.71 ± 0.14 and in optical yields of 28.8 ± 5.2% and 15 ± 5%, respectively. The ADPM rearrangement of (-)-(S)-4 to the trans- and cis-configurated products occurs with a preponderance of the path leading to retention of configuration at the pivot atom (C(1′) in the reactant and C(2′) in the products) for (-)-trans-7 and to inversion of configuration for (+)-cis-7, respectively. The results can be rationalized by assuming reaction paths which involve the occurrence of discrete 1,4- and 1,3-diradicals (cf. Schemes 10, 12, and 13). A general analysis of such ADPM rearrangements which allows the classification of these photochemical reactions in terms of borderline cases is presented (Scheme 14). It is found that the optical yields in these ‘step-by-step’ rearrangements are determined by the first step, i.e. by the disrotatory bond formation between C(2) of the aromatic moiety and C(2′) of the allylic side chain leading to the generation of the 1,4-diradicals. Moderation of the optical yields can occur in the ring closure of the 1,3-diradicals to the final products, which may take place with different trans/cis-ratios for the individual 1,3-diradicals. Compounds (-)-trans-7 as well as (+)-cis-7 easily undergo the well-known photochemical trans/cis-isomerization. It mainly leads to racemization. However, a small part of the molecules shows trans/cis-isomerization with inversion of configuration at C(1′), which is best explained by a photochemical cleavage of the C(1′)-C(3′) bond.

Notes: [fac-Re(bpy) (CO)3Cl] (bpy = 2,2′-bipyridine) is an efficient homogeneous catalyst for the selective and sustained photochemical or electrochemical reduction of CO2 to CO. A quantum yield of 14% and a faradic efficiency of 98% were measured in the presence of excess Cl- ions. The photochemical process took place under visible-light irradiation and consumed a tertiary amine as electron donor. A formato-rhenium complex was isolated in the absence of excess Cl- ions. Substitution by Cl- ion generated free formate, but no CO was detected. Luminescence measurements showed that the tertiary amine quenches the metal-to-ligand charge-transfer excited state of the rhenium complex via a reductive mechanism, with a rate constant of 3.4 × 107M-1S-1. The 19e-complex [Re(bpy) (CO)3X]- produced either photochemically or electrochemically appears to be the active precursor in the CO-generation process. Detailed spectroscopic studies on 13C-enriched carbonyl-rhenium and formato-rhenium complexes derived from 13C-enriched CO2 were performed in order to confirm the origin of the products and to study the exchange of the ligands. A mechanism for the present CO2 photoreduction process is presented; it involves separate pathways for CO and formate generation, in which the [Re(bpy) (CO)3X] complex plays the role of both the photoactive and the catalytic center.

Notes: Reaction of 3-(Dimethylamino)-2H-azirines with 1,3-Thiazolidine-2-thioneReaction of 3-(dimethylamino)-2H-azirines 1 and 1,3-thiazolidine-2-thione (6) in MeCN at room temperature leads to a mixture of perhydroimidazo[4,3-b]thiazole-5-thiones 7 and N-[1-(4,5-dihydro-1,3-thiazol-2-yl)alkyl]-N′,N′-dimethylthioureas 8 (Scheme 2), whereas, in i-PrOH at ca. 60°, 8 is the only product (Scheme 4). It has been shown that, in polar solvents or under Me2NH catalysis, the primarily formed 7 isomerizes to 8 (Scheme 4). The hydrolysis of 7 and 8 leads to the same 2-thiohydantoine 9 (Scheme 3 and 5). The structure of 7a, 8c, and 9b has been established by X-ray crystallography (Chapt. 4). Reaction mechanisms for the formation and the hydrolysis of 7 and 8 are suggested.

Notes: Six sesquiterpenoids 1-6, formally derived from (+)-(S)-nerolidol by oxidative cyclization, have been isolated for the first time from commercial cabreuva oil. Whereas the two tetrahydrofurans 5 and 6 have already been described, the four bicyclic ethers (cabreuva oxides A-D) 1-4 are new. The structures of 1-4 are confirmed by synthesis and their absolute configurations are shown to be 3S. The organoleptic properties of the synthetic cabreuva oxides are discussed.

Notes: Three new bidesmosidic saponins 1-3 have been isolated from the berries of Phytolacca dodecandra L′HERIT (Phytolaccaeae). The structures have been established by spectroscopic (1H-NMR, 13C-NMR, FAB-MS, DCI-MS, and GC/MS) and chemical methods (acid, basic, and enzymatic hydrolysis). Saponins 1 and 3 are tetra- and pentaglycosides of oleanolic acid, whereas 2 is a tetraglycoside of bayogenin. The corresponding prosapogenins 1a-3a, obtained by cleavage of a glucose unit esterified at C(28), exhibited strong molluscicidal activity against schistosomiasis-transmitting snails.

Notes: A new method for alkaloid synthesis is described. The rhodium(II)-acetate-catalyzed decomposition of 3-(4-acetoxyphenyl)-1-diazo-4-(pyrrol-1-yl)-2-butanone (5d) gave 6-(4-acetoxyphenyl)-5,6-dihydro-7(8H)-indolizinone (6d) in 82% yield via an intramolecular carbenoid reaction. The latter compound was converted in four steps in 13% overall yield to (±)-ipalbidine (1b).

Notes: Separation of Enantiomers by Partition between Liquid Phases. Enantioselectivity of Diastereoisomeric Dimenthyl Tartarates towards α-Aminoalcohol SaltsThe enantioselectivity of the easily obtainable diastereoisomeric dimenthyl tartarates I and II towards the salts of a series of α-aminoalcohols 1-10 was investigated by partition between aqueous and lipophilic phase. The measured enantiomer distribution constants Q (=KA/KB) confirm the previously observed configurational relationships between the lipophilic tartarates and the preferentially extracted enantiomer of the hydrophilic ammonium slat. However, the (R,R)-ester I is appreciably more selective than its (S,S)-diastereoisomer II or other previously investigated esters. The tartarates I-III transport norephedrin salts through bulk lipophilic membranes with enantioselectivity comparable to that observed in partition experiments. The most enantioselective ester I can be used as an efficient mobile phase for preparative separation of norephedrine enantiomers by flash partition chromatography.

Notes: A synthesis of 1,2-cis-configurated, non-isosteric phosphonate analogues of aldose-1-phosphates is described. Treatment of 1-O-acyl-glycoses 1, 7, 13, and 19 with trialkyl phosphite in the presence of trimethylsilyl trifluoromethanesulfonate gave the 1,2-cis-configurated glycosylphosphonates 2, 4, 8, 10, 14, 16, 20, and 22 as the major anomers and the 1,2-trans-configurated glycosylphosphonates 3, 5, 9, 11, 15, 17, 21, and 23 as the minor anomers. The 1,2-cis-configurated phosphonates 4, 10, 16, and 22 were deprotected to give the (β-D-glucopyranosyl)phosphonate 6, the (β-D-mannopyranosyl)phosphonate 12, the (β-D-ribofuranosyl)phosphonate 18, and the (β-D-arabinofuranosyl)phosphonate 24, respectively, in high yields. The preferred formation of 1,2-cis-configurated phosphonates is explained by postulating an equilibrium between the anomeric phosphonium-salt intermediates (such as 25 and 26) and a stabilization of the cis-configurated salts through formation of a pentacoordinated species (such as 28).

Notes: The synthesis of the cyclopropyl silyl ketones 1-4 is described. The trimethylsilyl ketone 1 was prepared from geraniol ((E)-5) in ca. 10% overall yield by cyclopropanation leading to 6, CrO3 oxidation to the aldehyde 8, reaction of the latter with trimethylsilyl anion to 14A+B, and CrO3 oxidation to 1. Also for the (t-butyl)dimethylsilyl ketones 2-4, an efficient four-step synthesis with overall yields of 48%, 85%, and 13%, respectively, was elaborated, starting from the allylic alcohols (E)-5, and 23. The method of preparation involves as the key step a Wittig rearrangement of the silylallyl ethers ((E/Z)-20, 24) to the silyl alcohols ((E/Z)-21, 25), subsequent cyclopropanation (19A + B, 22A + B, 26), and oxidation to the cyclopropyl silyl ketones 2-4.