Library

Notes: The photohydration of phenylacetylene yields acetophenone enol as a transient primary product which was detected by flash photolysis. The identification of the transient intermediate rests on a quantitative comparison of its decay kinetics with that of authentic acetophenone enol generated by Norrish type-II photoelimination from γ-hydroxybutyrophenone in aqueous HCl and aqueous AcOH buffer solutions.

Notes: With the aim to investigate the influence of structural isomerism on the mesomorphic thermal stability in main chain thermotropic polycondensates, a series of poly(azomethines) and low molecular weight models have been prepared. The model compounds exhibit smectic and/or nematic mesophases whose stabilites are very sensitive to structural modifications. On the basis of the above results, monomers 2, 5, 6, 8, 9, 23, 25, and 26 were selected to synthesize oligomers 27-23. The oligomer 33 obtained from the nonsymmetric diamine 23 has a lower melting point than the symmetric oligomer 28, but a similar liquid crystalline range.

Notes: The syntheses, photolyses, and thermolyses of the α,β-unsaturated silyl ketones (E/Z)-7, (E)-8, and (E)-9 are described. On n,π*-excitation (λ 〉 347 mm), the aforementioned compounds undergo (E/Z)-isomerization followed by γ-H abstraction. The intermediate enols are trapped intermolecularly by siloxycarbenes leading to the dimeric acetals 27A + B, 30A + B, and 31A + B. In addition, the acylsilanes (E/Z)-7 undergo photoisomerization by δ-H abstraction furnishing the acylsilanes 29A + B. Flash vacuum thermolyses (FVT) of (E/Z)-7, (E/Z)-8, and (E)-9 give rise to intramolecular reactions of the siloxycarbene intermediates. Thus, FVT (520°) of (E)- and (Z)-7 selectively leads to the enol silyl ethers 32 and (E)-33, respectively, arising from carbene insertion into an allylic C--H bond. FVT of (E/Z)-8 (560°) and (E)-9 (600°) affords the trienol silyl ethers 34A + B and the cyclic silyl ethers 37A + B, respectively, which are formed by CH insertion of the siloxycarbenes. As further products of (E)-8 and (E)-9, the bicyclic enol ethers 35 and 36 are formed, presumably via siloxycarbene addition to the cyclohexene C=C bond.

Notes: Synthesis of (Methylthio)penam Derivatives via Keten Addition onto 4,5-Dihydro-5-(methylthio)-1,3-thiazolesThe 4,5-dihydro-5-(methylthio)-2-phenyl-1,3-thiazoles 3a and 3b, easily prepared from the corresponding 1,3-thiazol-5(4H)-thiones and MeLi, react with dichloroacetyl chloride (5a) and acidoacetyl chloride (5b) in the presence of Et3N to give (methylthio)penam derivatives 6 (Table 1). The reaction mechanism is either a [2 + 2] cycloaddition of in situ generated ketene or a two-step reaction (Scheme 2). The structure of 6f has been confirmed by X-ray crystallography (Fig. 2). The relative configuration of 6a-e follow from comparison of their 1H-NMR spectra with those of 6f (Fig. 1). The 6-azidopenams 6d and 6f have been reduced to aminopenams 8a and 8b, respectively. Acylation of 8a with phenacetyl chloride yields 9 (Scheme 4).

Notes: Since we found certain structural features of triaziridine (1) obtained by MNDO calculations to be in qualitative agreement with those derived earlier from ab initio calculations, we used the MNDO method to derive properties of formyltriaziridine (2) and 1-formyl-2,3-diisopropyltriaziridine (3) as models for the preparatively known 2,3-dialkyl-triaziridine-1-carboxylates 4 and 5. The main results are: (a) The triaziridine N-atoms with H, alkyl, or formyl as substituents (see 2 and 3) are pyramidal. N(1) carrying the formyl group is flatter than N(2) and N(3) with H or alkyl substitent. Bond lengths and angles at N(2) and N(3) are almost identical with those calculated for the N-atoms of 1. (b) The MNDO inversion barriers at the H-substituted N(2) and N(3) of 2 are higher than those at the formyl-substituted N(1), but similar to the ab initio barriers at the N-atoms of 1. (c) The MNDO inversion barriers at N(1) of 2 and 3 are 53 to 92 kJ/mol, whereas the rotation barriers around the N(1)-C(4) bond are 7 to 23 kJ/mol; thus, the previously observed dynamic NMR phenomena in trans-2,3-diisopropyltriaziridine-carboxylates (5) can now be assigned to the slowing down of N(1) inversion rather than N(1)-C(4) rotation.

Notes: Synthesis and Structure Elucidation of Merucathinone and Synthesis of Cathinone. Constituents of Catha edulis FORSK.Starting from L-alanine, two constituents of Catha edulis FORSK., (S)-4-amino-1-phenylpent-1-en-3-on ((S)-3; merucathinone) and (S)-2-amino-1-phenylpropan-1-on ((S)-1; cathinone) were synthesized.

Notes: The relative configuration of the title compounds has been determined by 1H-NMR measurements at 300 MHz. In contradistinction to prevailing opinion, it was found that 4-oxo derivatives prefer the cis-configuration. While the cis/trans ratio is 82:18 for the parent 1,2,3,4,4a,9,10,10a-octahydrophenanthrene-4,9-dione, the trans-isomers of C(5)-substituted derivatives cannot be detected under the conditions of equilibration. The cis-configuration is retained upon acetalization of the 4-oxo derivative. A warning is issued regarding the assigned configurations of certain intermediates in the Elad-Ginsburg synthesis of morphine.

Notes: The Mediterranean stolonifer Sarcodictyon roseum ( = Rolandia rosea) (Cnidaria, Anthozoa, Alcyonaria, Stolonifera, Clavulariidae) contains the first example of a chiral, optically active prenyl derivative of a reduced benzoquinone, sarcodictyenone (= (+)-(4R*,5R*)-5-geranylgeranyl-4-hydroxy-2-methylcyclohex-2-en-1-one; (+)-1a).

Notes: Nucleophilic Addition of Lithiumorganyles to N,N-Diethyl-10-(trimethylsilyl)-1,6-methano[10]annulene-2-carboxamideReaction of lithiumorganyles with N,N-diethyl-10-(trimethylsilyl)-1,6-methano[10]annulene-2-carboxamide followed by quenching with H2O or MeI yields 2,3-dihydro derivatives of 1,6-methano[10]annulene.

Notes: Synthesis of 3-Nitro-1,1-bis(triisopropylsilyl)-1H-cyclopropabenzene and Derivatives of Azocyclopropabenzene1,1-Bis(triisopropylsilyl)-1H-cyclopropabenzene (4) can be nitrated at C(3) without opening of the three-membered ring. Further functionalized cyclopropabenzenes are available in this way.

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: 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: 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: 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: 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: 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: 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 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: 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: C45-and C50-Carotenoids: Synthesis of (S)-TrisanhydrobacterioruberinThe Synthesis of (S)-trisanhydrobacterioruberin ((S)-1) is reported.

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: The fast-atom-bombardment mass spectra (FAB-MS) of a series of ribo- and deoxyribonucleosides and -nucleotides were examined in both positive-ion and negative-ion modes. Behaviour of cytosine analogs having unnatural bases (2(1H)-pyrimidone, 2(1H)-pyridinone, and 4-amino-2(1H)-pyridinone) was similar to that of compounds having naturally occurring bases. Nucleotides protected by dimethoxytrityl and p-chlorophenyl groups were also investigated using this technique. Use of negative-ion mode reduces interference from positive counter-ions (e.g., Na+) and allows rapid sequence determination of simple di- and trinucleotides.

Notes: The tetra(tert-butyl)[14]annuleno[14]annulene 1 is transformed, via alkali metal reduction, into its radical monoanion, dianion, radical trianion, and tetraanion. The paramagnetic species are characterized by ESR and ENDOR spectroscopy and the diamagnetic species by 1H- and 13C-NMR spectroscopy. Well-resolved ESR and NMR spectra can only be obtained, if the reduction is carefully monitored. For the interpretation of the data, the ions derived from the structurally related [14]- and [22]annulenes 3 and 5 as well from the tetra(tert-butyl)[14]annuleno[18]annulene 2 serve as suitable model compounds. While the behavior of the neutral annulenoannulene 1 is governed by that of the [14]annulene-subunit, the corresponding ionic systems can best be described as macrocyclic perimeters. This outcome can be rationalized by the nodal properties of the frontier MO's.

Notes: The electronic structure of [4.2.2]propella-2,4,7,9-tetraene (1), 2,5-etheno[4.2.2]propella-3,7,9-triene (2), and of several hydrogenated derivatives of 2 has been investigated using He(I) PE spectroscopy and MO calculations. It is found that in 2 the 1,4-cyclohexadiene moiety interacts considerably with the bicyclo[2.2.0]hexadiene unit, while in 1 the interaction between the butadiene fragment and the Dewar benzene unit is minute. The syntheses of 3-5 are reported.

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: 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 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: 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: 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: EtAlCl2-promoted additions of organocopper reagents to camphor-derived, conjugated N-enoyl-sultams gave saturated and olefinic β-silylcarboxyl derivatives with high diastereodifferentiation. Nondestructive removal of the chiral auxiliary followed by oxidative Si-C bond cleavage furnished enantiomerically pure acetate-derived aldols and propionate-derived ‘anti’ -aldols (via silyl-directed α-methylation).

Notes: Synthesis of 6,7-Dihydro-2H-pyrimido[6,1-a]isoquinolin-4(3H)-ones and Analogous Compounds and their Activity as Blood-Platelet InhibitorsThe synthesis of 6,7-dihydro-2H-pyrimido[6,1-a]isoquinolin-4(3H)-ones and of analogous compounds is described. These compounds are powerful phosphodiesterase inhibitors and, therefore, inhibit blood-platelet aggregation independent of the agonist. They exhibit, too, cardiac activities. However, there is evidence for selective action. A structure-activity relationship for platelet-aggregation inhibitors is discussed.

Notes: Enantiomerically Pure Pyrrolidine Derivatives from trans-4-Hydroxy-L-proline by Electrochemical Oxidative Decarboxylation and Titanium-Tetrachloride-Mediated Reaction with NucleophilesPreparative electrolysis of N-methoxycarbonyl-O-[(t-butyl)dimethylsilyl]hydroxyproline 4 in MeOH leads to substitution of the COOH by a MeO group (oxidative decarboxylation). The mixture 5 of the two diastereoisomers (ca 1:1) thus obtained was reacted in CH2Cl2 with nucleophilic silylated compounds (such as allylsilane, silyl cyanide and 1-phenyl-1-silyloxyethane) or with trimethyl phosphite in the presence of TiCl4 to give 2-allyl-, 2-cyano-, 2-(2-oxo-2-phenylethyl)- and 2-phosphono-substituted hydroxypyrrolidines, respectively, with high diastereoselectivities (≥ 90%, products 6-12). The configuration of two of the products (6/7 and 8/9) was shown to be cis.

Notes: Cyclophane-Metal Complexes: Synthesis and Crystal Structure of ([3.3]Paracyclophane)gallium(I) Tetrabromogallate(III)[3.3]Paracyclophane forms 1:1 complexes 2a and 2b with both Ga[GaCl4] and Ga[GaBr4]. The crystalline products obtained from toluene solution at room temperature are much less sensitive to air and moisture than most other arene complexes of Ga(I). Solubilities in standard organic solvents are very low, suggesting coordination polymers. The X-ray diffraction analysis of 2b confirms the presence of a two-dimensional network. Both aromatic rings of each cyclophane molecule are η6-coordinated from the outer side to Ga(I)-atoms. The position of these metal cations is 2.75 Å above the ring centres. The arene rings are parallel within each cyclophane, but tilted by 48.5° with respect to those of the neighbouring cyclophane. The coordination sphere of the Ga(I) centres is completed by two Br-atoms of two GaBr4- anions, which link the Ga(I) cations to give … Ga[GaBr4] Ga[GaBr4]Ga … strands. The double interconnection of the Ga(I)-atoms gives rise to a two-dimensional sheet structure, which is thus different from the structure of the previously described Ga[GaBr4] complex of [2.2]paracyclophane, where a three-dimensional network was observed.

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: 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: 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: 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: 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: The Stereochemistry of the Nucleophilie Opening of the Cyclopropane Ring in the four Diastereoisomeric Lanugons J (Spirocoleons)Methanolysis of the spiro(methylcyclopropane) moiety in the four diastereoisomeric lanugons J 3 (13S, 15R), 4 (13R,15R), 5 (13S,15S), and 6 (13R,15S) is shown to proceed stereospecifically with inversion of the configuration at the attacked C-atom (C(15)). The resulting epimeric 2-methoxypropyl-substituted hydroxy-1,4-benzoquinones (royleanones) 7a/8a (monomethoxy derivatives) and 7b/8b (dimethoxy derivatives) could be separated by HPLC using the recently described ‘Non-Aqueous Cation Exchange System’. Respective pairs of 1H-NMR spectra exhibit minute but significant differences in the ABMX3 part of the 2-methoxypropyl group. The final structure assignment is based on a single-crystal X-ray analysis of the dimethoxyroyleanone 7b, whose absolute configuration was established by chiroptical correlation with known abietanoids. Thus, methanolysis of 3 and 4 ((R)-configuration at the reaction centre) yielded the royleanones 7a and 7b with (S)-configuration, whereas analogous treatment of 5 and 6 ((S)-configuration at the reaction centre) led to the corresponding derivatives 8a and 8b both having the (R)-configuration in the 2-methoxypropyl side chain.

Notes: Hydrogenation of the ketone group in di-O-benzylderivative (8) of the known macrocyclic lactone zeralenone (7) using a novel chiral borane complex 3. BH3, prepared in situ, proceeded at lower temperatures with moderate diastereoselectivity (∼40%, d. e. at -60°). Unsaturated diastereomers 9 and 10 were separated, and 9 converted into zeranol (11), a known anabolic agent. Restricted conformational mobility at lower temperatures is assumed for the intermediate 8 on the basis of the temperature-dependent CD spectra of its acetyl congeners 18 and 19. X-Ray structure analysis of 7-O-acetylderivative (13) of 11 revealed the (R)-configuration at C(7). Two crystallographically independent H2O molecules are involved in the H-bonds, one of them (O(21)) rises the helices of the molecules of 13 along b. Small positive torsional angle [C(16)-]C(161)-C(1) [=O] (+19.3°), transoid(E) conformation of the lactone group, and nearly achiral arrangement of the C(11)-C(12) bond (torsional angle [C(11)-]C(12)-C(121)[C(161)] is -93°) are the main conformational features that differentiate the macrocylic RAL (resorcinic-acid lactone) derivatives from the 6-membered lactone derivative 20, studied earlier by CD. Consequently, the rules developed for the CD effects within conjugation band (around 270 nm), and n→π* band (around 255 nm) of the latter compound, cannot be applied the macrocyclic lactones.

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: (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: 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: Novel Heterocycles: Tetrazinodi(heteroarenes), Synthesis and StructureA series of 7 new symmetric tetrazinodi(heteroarenes) is obtained in a two-step synthesis by N-aminating heterocyclic compounds substituted with a leaving group and by treating the latter with an organic or inorganic base. The new compounds are characterized, and the postulated structures are confirmed by X-ray analysis of a representative example.

Notes: Structure and Reactivity of Xanthocorrinoids. C(15) Hydroxylation of the Corrin Chromophore on Reaction of Cyanocob(III)alamin with Udenfriend's ReagentHydroxy-corrinoid 4 represents a new type of corrin derivatives whose chromophore is identical with that of products formed on bacterial degradation of cyanocob(III)alamin (1). In vitro, 4 is obtained by O2 oxidation of 1 in the presence of ascorbic acid and cupric ions.

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: 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: The two bis-macrocycles 4 and 5 in which the tetraaza units are separated by a chain of different length, have been synthesized using 1,4,7-tritosyl-1,4,7,11-tetraazacyclotetradecane as starting compound and bifunctional alkylating agents. The bis-macrocycles give binuclear complexes with Ni2+ and Cu2+, the properties of which have been studied to obtain information about the interaction of the two subunits as a function of the distance. The VIS spectra of the Ni2+ and Cu2+ complexes indicate that both metal ions are in a square-planar geometry as expected from the results of the analogous complexes with 1,4,7,11-tetraazacyclotetradecane 7. Cyclic voltammetry and differential pulse polarography of the binuclear Ni2+complexes in CH3CN show a single two-electron step for ligand 5, whereas two distinct one-electron redox processes can be observed for ligand 4, indicating that the two metal ions interact with each other when the chain length is shorter. Similarly, the EPR studies of frozen solutions of the binuclear Cu2+ complexes clearly show that a magnetic dipolar interaction between the two paramagnetic centers exists, and that the strength of it depends upon the length of the bridge. Finally, from the X-ray structures of the binuclear Ni2+ complexes with 4 and 5, it is seen that the two rings are kept apart as far as possible, the distances between the two metal ions determined in the solid correlate well with the observations in solution.

Notes: The X-ray crystal structures of bis(9,9′-spirobifluorene)-26-crown-4βbenzene solvate (monoclinic, a = 15.47 Å, b 11.265 Å, c = 15.220 Å, β = 91.54°, space group C2) and bis(9,9′-spirobifluorene)-32-crown-6·dichloromethane solvate (tetragonal, a = 20.958 Å, c = 11.779 Å, space group P41212) are described. Both compounds act as enantioselective ionophores for α-aminoalcohols.

Notes: C45- and C50-Carotenoids: Synthesis of Optically Active Cyclic C20-Building Blocks and of (2R,2′R)-2,2′-Bis(4-hydroxy-3-methyl-2-butenyl)-β,β-carotene ( = C.p. 450)The synthesis of the optically active C20-building blocks (R)-26 and (R)-39 and of the optically active cyclic C50-carotenoid C.p. 450 (3) starting from (-)-β-pinene is reported.

Notes: The Thermal, Catalytic, and Photochemical Denitrogenation of 1-Diazo-3-(1-methylcyclopenta-2,4-dienyl)-2-propanoneThe synthesis of the title compound 12 is described. This diazoketone, distinguished by its Cs-symmetry and by a built-in cisoid diene unit, gives 5-methyltricyclo[3.3.0.02,8]oct-6-ene-3-one (13) when subjected to thermal or catalytic denitrogenation with rhodium (II) acetate or copper (II) acetylacetonate. Direct irradiation of 12 at 350 nm causes Wolff rearrangement, whereas the benzophenone-sensitized photolysis gives again ketone 13. A 1,4-carbene or carbenoid addition was never observed under the conditions described. The ketone 13 equilibrates thermally or under base catalysis with 1-methyltricyclo[3.3.0.02,8]oct-6-ene-3-one (17). The key step of this apparent CH3 migration is shown to be a Cope rearrangement of the corresponding enols (hydroxysemibullvalenes).

Notes: From bergamot oil (Citrus bergamia RISSO), (-)-(4S, 8R)-8-epi-α-bisabolol (2) and (-)-(4R, 8S)-4-epi-β-bisabolol (3) were isolated. The absolute configuration of their stereoisomers 4 and 5 was established by an enantioselective synthesis starting from (-)-(S)-p-mentha-1,8-dien-4-ol.

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: 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: 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: Aus der Dreikomponentenreaktion von Cyclopentadien (1) mit s-Triazin (2) und einem sekundären Amin 4 gehen die cyclisch N,N-disubstituierten Pentafulven-6-amine 5 und die cyclisch N1,N1-disubstituierten N2-(6-Pentafulvenyl)formamidine 7 hervor. Unter den biologischen Eigenschaften der neuen Verbindungen ist besonders die anthelminthische Wirkung von 5d interessant.

Notes: In addition to the already known asteronylpentaglycoside sulfate (5) and ovarian asterosaponin 1 (6), two new genuine asterosaponins named versicoside B (3) and C (4) have been isolated from the starfish Asterias amurensis [cf.] versicolor Sladen and characterized. Their structures have been elucidated as the monosodium salt of 6α-[(O-β-D-galactopyranosyl-(1→3)-O-β-D-fucopyranosyl-(1→2)-O-β-D-galactopyranosyl-(1→4)-O-[β-D-quinovopyranosyl-(1→2)]-O-β-D-xylopyranosyl-(1→3)-β-D-quinovopyranosyl)oxy]-20ξ-hydroxy-3β-(sulfooxy)-5α,24ξ-ergost-9(11)-en-23-one (3) and the monosodium salt of 6α-[(O-β-D-fucopyranosyl-(1→2)-O-β-D-galactopyranosyl-(1→4)-O-[β-D-quinovopyranosyl-(1→2)]-O-β-D-xylopyranosyl-(1→3)-β-D-quinovopyranosyl)oxy]-20→-hydroxy-3β-(sulfooxy)-5α,24ξ-ergost-9(11)-en-23-one (4). Apart from the conventional analytical methods, negative fast-atom bombardment (negative FAB) mass spectrometry was successfully used for the first time for determination and confirmation of the structure of the natural oligoglycoside sulfates.

Notes: On the Synthesis and Reactions of New Vinylogous ChloroformamidinesThe (chloromethylene)propanedinitriles 1 and 2 react with the [bis(dialkylamino)methylene]-propanedinitriles 3a-g to give the vinylogous chloroformamidines 4a-g and 5a, d, respectively. Hydrolysis of compound 4a leads to the product 6. Treatment of 4a with the sulfur nucleophiles 12a-e, 11a-c, 8, and 9 results in the compounds 14a-e, 13a-c, 7, and 10.

Notes: Umwandlung von Alkoholen in primäre Amine, eine neue Mitsunobu-Version der Gabriel-SynthesePrimäre und sekundäre Alkohole liefern die entsprechenden Amin-hydrochloride 3 mit guten Ausbeuten (60-85%), wenn sie unter milden Bedingungen mit N-(Diethoxyphosphoryl)-carbamidsäure-tert-butylester (1) in Gegenwart von Azodicarbonsäure-diethylester/Triphenylphosphan umgesetzt und danach die entstandenen N-Alkyl-N-(diethoxyphosphoryl)carbamidsäureester 2 mit gasförmigem HCl gespalten werden. Die Stereochemie dieser Reaktion wird untersucht.

Notes: Drei Vertreter der großen Klasse alicyclischer Diterpene, Mikanifuran (6), Centipedasäure-methylester (23) und Koanoadmantasäure-methylester (33), werden ausgehend von den Sulfonen 4, 15 und 28 synthetisch dargestellt. Die spektroskopischen Daten der erhaltenen Verbindungen stimmen mit denen der Naturstoffe überein.

Notes: Durch Röntgenstrukturanalyse von (R)-1-[3-Cyclohexyl-3-hydroxy-3-phenylpropyl]-1-methyl-pyrrolidiniumiodid [(R)-Tricyclamoliodid, (R)-2a] wurden die absoluten Konfigurationen der Enantiomere der Antimuskarinika Procyclidin (1a) und Tricyclamoliodid (2a) bestimmt. (R)-1a und (R)-2a sind etwa 380-bzw. 90mal stärker antimuskarinisch wirksam (isoliertes Meerschweinchen-Ileum) als die entsprechenden (S)-konfigurierten Enantiomere.

Notes: NMR-spektroskopische Konformationsuntersuchungen an den zehn cyclischen, in den Seitenketten geschützten Pentapeptidanalogen des Thymopoietins cyclo[-(D,L-Tyr/Trp/D-Phe)-(Arg/D-Lys)-(Arg/D,L-Lys)-(Asp/Glu)-(D,L)-Val-] (c1-c10) werden beschrieben. Wie die Temperatur- und Lösungsmittelabhängigkeit der NH-Signale, Kopplungskonstanten, NOE-Effekte und 15N-NMR-Spektren zeigen, liegen alle Cyclopeptide in einer βII′γ-Struktur vor. Während aus dem Austausch aromatischer Aminosäuren keine Unterschiede in den spektroskopischen Parametern resultieren, deuten die beim Austausch von Asp gegen Glu sich ändernden Parameter geringere Flexibilität des Ringgerüsts an. Die Seitenkettenkonformationen der aromatischen Aminosäuren Tyr und Trp sowie von Asp werden kurz diskutiert. Aufgrund der vorliegenden Untersuchungen kann eine gestreckte Konformation des linearen Fragments 32 - 36 als biologisch aktive Konformation ausgeschlossen werden.

Notes: Die Titelverbindung 8b, ein Zwischenprodukt der beabsichtigten Partialsynthese von Bilobalid (10), wird durch Abbau von Ginkgolid A (1) gewonnen. Durch Röntgenstrukturanalyse von 14,15,16-Trinorginkgolid A (7) wird die Struktur der Ringe B - E der Ginkgolide bestätigt.

Notes: Bei der N-Iodsuccinimid-Glycosylierung von Methyl-3,4-di-O-acetyl-1,5-anhydro-2-desoxy-D-arabino-hex-1-enouronat (8) mit 1,6 : 2,3-Dianhydro-β-D-mannopyranose (7) werden als Disaccharide das kristalline 2′-Desoxy-2′-iod-β-D-gluco-Derivat 9 und sein α-D-manno-Isomer 10 mit ungewöhnlicher Halbbootkonformation im nichtreduzierenden Ring im Verhältnis ca. 1 : 1 gewonnen. Vergleichbare Befunde ergeben sich bei der Reaktion von 8 mit dem 1,6-Anhydro-2-desoxy-Saccharid 15a zu den interglycosidisch anomeren Trisacchariden 16 und 17. Nach der milden Anhydroringöffnung von 16 zum Benzylglycosid 18 wird durch gleichzeitige Hydrogenolyse und Methoxycarbonyl-Reduktion sowie eine nachfolgende regioselektive Veresterung das 6,6′-Ditosylat 20 gewonnen. In einem abschließenden Reduktionsschritt wird das 2,2′,6,6′-Tetradesoxydisaccharid 22 mit D-arabino-Konfiguration in beiden Ringen erhalten, welches das terminale Disaccharidfragment B - C in verschiedenen Orthosomycinen wie z. B. 1 bis 3 darstellt.

Notes: Die Darstellung der Ketone 4a - e sowie deren Umsetzung mit Methylmagnesiumiodid werden beschrieben. Für die bei einigen dieser Grignard-Additionen auftretende Umlagerung zum 6,7-Diazabicyclo[3.2.1]octan-System wird ein Mechanismus aufgestellt. - Die Dehydratisierung der Alkohole 12d, 14a, 17a, b, g und h mit Trichlorphosphanoxid erfolgt unter stereokontrollierter Umlagerung zum Bicyclo[3.2.1]octan-System mit Wanderung der zur Hydroxyfunktion antiperiplanaren Gruppierung. - Je nach Belichtungsbedingungen erhält man bei der Photoisomerisierung von 4a, c und e die Tricyclooctan-Derivate 40a, b bzw. d oder die Bicycloheptan-Derivate 42a, b bzw. d.

Notes: Reactions of 3,7,7-Trimethyl-4-methylenebicyclo[4.1.0]hept-2-ene with DienophilesThe preparation of the title compound 2b is described. Treatment of 2b with some dienophiles leads to the adducts 4a, b and 6b, c via ene reactions. 2b can be rearranged to give the cycloheptatriene 8.

Notes: Reactions of Phenyl 4-Chromone-3-sulfonate with AmidinesThe amidines 2a - e undergo with phenyl 4-chromone-3-sulfonate (1) a ring transformation to give the benzoxathiino-pyrimidines 6a - e.

Notes: Durch Anwendung der 13C-NMR-Spektroskopie (DEPT) und spezieller NMR-Techniken (CH- und HH-COSY) bei Taxin B, dem nativen Hauptalkaloid aus Taxus baccata, sowie bei dem stabileren Diacetyltaxin B wurden die gleichen Strukturformeln ermittelt, wie sie von anderen Autoren dem hypothetischen Taxin-I und seinem Diacetat zugeordnet wurden.

Notes: A practical synthesis of (+)- and (-)-verrucarinolactone (2) and epiverrucarinolactone (1) from (R)-2,3-O-isopropylideneglyceraldehyde via the key intermediates 3a/b is described.

Notes: Die Substitution in 4- und 6-Position des Azulens (1) wird durch Einsatz neuer Nucleophile (dehydrierende Aufarbeitung) erweitert: Lithiierte Methylphosphonsäureester und Formaldehyd-dithioacetale liefern die 4- und 6-Azulenylmethylphosphonsäureester 4 - 7 und 4- und 6-Azulencarbaldehyd-dithioacetale 11, 15 und 25. Diese lassen sich zu den entsprechenden Aldehyden spalten. Zweckmäßiger werden 4- und 6-Azulencarbaldehyd (23 und 27) über die Reaktion von 1 mit Lithium-(diethylamino)acetonitril synthetisiert. Das Verhältnis 4:6-Substitution in Abhängigkeit vom Nucleophil wird diskutiert.

Notes: 5(1H)-Pyrromethenones 3 have been reduced with sodium dithionite to give 5(2H)-dipyrrylmethanones 4 in very good yields. Some of the conditions to optimize this reduction have been studied.

Notes: Epoxidierung von rac-β-Curcumen (1) ergibt ein Gemisch, das neben anderen Produkten die Monoepoxide 2 - 4 und 6 im Verhältnis 4:1:5:1 enthält. - Die nichtkatalysierte Diels-Alder-Reaktion von Isopren (10) mit 3-Butin-2-on (11) führt zu einem Gemisch der Ketone 12 - 15 mit einem hohen Anteil des 1,5-Isomeren 13 sowie der Acetophenone 14 und 15. Durch TiCl4-Katalyse kann die Regioselektivität 12/13 auf 94:6 verbessert werden.

Notes: 5-(Acylamino)-2-methyl-4-thiazolecarboxamides 1 have been converted into a series of N-arylthiazolo[5,4-d]pyrimidin-7-amines 2 and 9-aryl-1,9-dihydro-6H-purine-6-thiones 3 by heating in a mixture of diphosphorus pentaoxide, triethylamine hydrochloride, and an appropriate substituted aniline at 240°C for 2 min and then at 160°C for 1 h. The ratio of 2 and 3 depends on the aniline and thiazole used.

Notes: Dichlor-1,3-bis(sulfonyl)cyclopentane (z.B. 12, 14, 19) sind durch Addition von Sulfensäurechloriden an Cyclopentadien und nachfolgende Oxidation erhältlich. Regio- und Stereoselektivität hängen von der Reihenfolge der einzelnen Reaktionsschritte ab. Durch HCl-Eliminierung erhält man daraus die 1,3-Bis(sulfonyl)cyclopentadienide 2, die beim Ansäuern die stabilen 1,3-Bis(sulfonyl)cyclopentadiene 3 liefern. 3-Chlor-4,5-bis(sulfonyl)cyclopentene 24 entstehen bei - 50 bis - 60°C aus Thallium(I)-cyclopentadienid (20) und Sulfensäure-chloriden mit anschließender Oxidation. HCl-Eliminierung führt zu den 1,2-Bis(sulfonyl)cyclopentadieniden 26, die beim Ansäuern in die Dimeren 27 übergehen.

Notes: The macrodiolide antibiotic elaiophylin (6, Scheme 1) is converted into an aglycone 8a by acid-catalysed cleavage of the deoxyfucoses in methanol, with replacement of two lactol OH-groups by OCH3 (C-11 and C-11′). The di-O-methylelaiophylidene (8a), a C2-symmetrical macrodiolide with 2 × 11 stereogenic units, was synthesised from (R)-3-hydroxy-butanoate (from the biopolymer PHB) and (S)-malic ester, using diastereoselective steps for the generation of the other stereogenic units. The key intermediates (Scheme 2) are the macrocyclic dialdehyde 10 (cf. 26, 27; 2 × 5 stereogenic units) and the silyl-protected dihydroxy ketone derivative 11 (cf. 34, 35; 3 stereogenic units). These two intermediates almost statistically were subjected to aldol coupling with relative topicity ul, using the Z-boron enolate of the ketone, to give the two C2-symmetrical and the asymmetric aldol (40a, b, c), one of which furnished the aglycone 8a upon acid-catalysed methanolysis (Fig. 1 and 2, NMR spectra). The diastereoselective key steps, by which three of the six new asymmetric carbon atoms are created, are α-alkylations of β-hydroxy ester or lactone alkoxide-enolates (malic acid → 12 and 15 → 16 in the dialdehyde synthesis, hydroxybutanoic acid → 29 in the ketone preparation).

Notes: Es wird die Herstellung der Titelverbindungen 5 durch Bromierung-Dehydrobromierung entsprechender 5-Alkyl-1,2,3-thiadiazole 3, ihre spektroskopische Charakterisierung und ihre Umsetzung mit 4-Phenyl-4H-1,2,4-triazol-3,5-dion (6) zu 7, 8 beschrieben.

Notes: Die Titelverbindungen 5 werden aus entsprechenden Alkylderivaten durch Bromierung/Dehydrobromierung (Weg A) oder durch Wittig-Reaktion (Weg B) dargestellt. Mit 4-Phenyl-4H-1,2,4-triazol-3,5-dion entstehen unter Erhaltung des Thiadiazolrings die Monoaddukte 12.

Notes: As nicotinamide coenzyme models the [2.2](2,5)pyridinophanes 3-6 were prepared which consist of two interacting nicotinic ester units in the four different orientations possible. 3-6 were obtained by photolytic sulfur extrusion from the corresponding dithia-[3.3](2,5)pyridinophanes 18-21 the syntheses of which are described.  -  The molecular structures for all four isomers 3-6 were determined by X-ray analysis. The sterical interactions and some spectroscopic properties of these compounds are discussed on the basis of the structure determinations.

Notes: β-Aroyl-α-(arylmethylen)propionsäurenKondensation der β-Aroylpropionsäuren 2a-d mit Furfural (1) führt zu (E,Z)-Gemischen der Enollactone 3a-d. Die Zuordnung zur (E)- oder (Z)-Reihe und das Isomerenverhältnis wurden durch hochaufgelöste 1H-NMR-Spektren bestimmt.

Notes: Die Pentosen D-Ribose (1), D-Xylose (3) und D-Lyxose (8) reagieren mit Tetracyanethylen (TCNE) und Ethanol in flüssigem Fluorwasserstoff in hohen Ausbeuten zu den entsprechend konfigurierten 2-[Perhydro-6-hydroxy-5-(hydroxymethyl)furo[2,3-d]oxazol-2-yliden]cyanessigsäureestern (2, 4 und 10). D-Arabinose (9) liefert neben dem furanoiden Hauptprodukt 11 auch das Isomer 12 mit pyranoidem Kohlenhydratanteil. D-Glucose (13) reagiert dagegen hauptsächlich zum pyranoiden Produkt 14 und in geringen Anteilen zum furanoiden Bicyclus 15. Die Synthese läßt sich auch auf andere Aldohexosen übertragen. D-Fructose (16) ergibt neben 18, die beiden Spiroverbindungen 17 und 19. - Die Struktur von 4 wurde durch eine Röntgenstrukturanalyse abgesichert.

Notes: Ausgehend von 1,5-Anhydro-2-desoxy-D-arabino-hex-1-enitol wird die peracetylierte 2,6-Didesoxy-D-arabino-Verbindung 7 erhalten und mit Bromtrimethylsilan zu dem sehr reaktiven Glycosylbromid 8 umgesetzt. Glycosylierung der Monoacetyl-2,6-didesoxy-D-lyxo-Komponenten 9 oder 10 mit 8 ergibt die anomeren 1 → 4- und 1 → 3-verknüpften Disaccharide 11 und 13. Durch 2D-NMR-Messungen können alle Protonen und Kohlenstoffatome in Mithramycindecaacetat (2) zugeordnet werden. Vergleiche der spektroskopischen Daten von 2 mit denen der peracetylierten Disaccharide 11 und 13 beweisen das Vorliegen einer β(1 → 3)-Bindung im B - A-Disaccharidfragment des Mithramycins.

Notes: Substituierte 1,4-Anthrachinone lassen sich wie die Stammverbindung 1 durch Phenol/Chinon-Addition zu Dimeren und potentiell chiralen cyclo-Trimeren umsetzen. Schlüsselverbindung der Synthese von cyclo-Trichinizarin (16b) ist der eine auffallende Tribolumineszenz und Phosphoreszenz aufweisende Ether 19b.

Notes: Die Synthesen der vier cyclischen Hexapeptide cyclo[-Arg(NO2)-Lys(Z)-Xxx(OBzl)-Val-Tyr-Gly-], c1: Xxx = Asp, c2: Xxx = Glu, cyclo[-Tyr-Val-Arg(NO2)-Lys(Z)-Xxx(OBzl)-D-Val-], c3: Xxx = Asp, c4: Xxx = Glu mit Thymopoietin-analogen Sequenzen werden beschrieben. Die linearen Vorstufen der Cyclen wurden nach klassischen Methoden der Peptidchemie synthetisiert. Die Cyclisierungen erfolgten mit der neu entwickelten Carbodiimid/DMAP-Methode. Konformationsuntersuchungen an den vier cyclischen Hexapeptiden erbrachten unterschiedliche Ergebnisse. Für die beiden Glycin enthaltenden Cyclohexapeptide c1 und c2 muß aufgrund der NMR-spektroskopischen Daten ein Gleichgewicht mehrerer Konformationen angenommen werden. Dagegen sind die D- und L-Valin enthaltenden Cyclohexapeptide c3 und c4 konformativ einheitlich. Die Konformationsanalyse zeigt. daß diese Cyclopeptide in einer βII′βI′-Struktur vorliegen.

Notes: Photoreaktionen von 2,4-Dinitro-6-(phenyliodonio)phenolat mit einigen Nucleophilen2,4-Dinitro-6-(phenyliodonio)phenolat (1) kann photochemisch mit Pyridin zu einem Pyridinium-Zwitterion 4, mit Phenylisocyanat zu einem 1,3-Benzoxathiol 5 und mit Thioharnstoffen zu λ3-Iodanen 6 umgesetzt werden. Ein denkbarer Mechanismus wird vorgeschlagen.

Notes: Indol und einige Methylderivate 1 lassen sich unter milden Bedingungen mit den Dialkoxycarbenium-tetrafluoroboraten 2 in meist guten Ausbeuten regioselektive acylieren. Mit dem Formylkation-Äquivalent 2a′ werden mit überschüssigem 1 auch die Bisindolycarbenium-tetrafluoroborate 13a - d erhalten.

Notes: Aktivierte Nitrile in der Heterocyclensynthese: Die Reaktion von Cyanthioacetamid mit aktivierten DoppelbindungssystemenDie Reaktion von Benzylidenmalononitrilen mit Cyanthioacetamid (1) ergibt je nach den Reaktionsbedingungen entweder Thiopyrane oder Pyridine. Die Strukturen der Reaktionsprodukte wurden mittels 13C-NMR aufgeklärt.

Notes: Synthesis of 2,3-Dihydro-1H-pyrrolizine-7-carbaldehyde, the Sex Pheromone DanaidalDanaidal (4) can easily be obtained in high yields from ethyl 2,3,5,6-tetrahydro-1H-pyrrolizine-7-carboxylate (1) via sulphur dehydrogenation or MnO2 oxidation, subsequent reduction to dehydrosupinidine (3), and further oxidation to the desired title compound 4.

Notes: Ammonium-cer(IV)-nitrat oxidiert dimere 1-Naphthole vom Typ 8 oder 10 in glatter Reaktion zu den Chinonen 9 oder 11. Aus diesen wurden durch Entalkylierung neben verschiedenen anderen potentiell natürlich vorkommenden dimeren Naphthazarin-Derivaten die Naturstoffe 8′-Hydroxy-isodiospyrin (22d) und Euclanon erhalten; die Struktur des letzteren wird durch die Synthese als 23e festgelegt.

Notes: Die Titelverbindung 1 wurde auf zwei verschiedenen Synthesewegen durch Cyclisierung zwischen Gly5 und Pro1 bzw. zwischen Phe4 und Gly5 erhalten. 1H-, 13C- und 15N-NMR-spektroskopische Untersuchungen in DMSO zeigen, daß das Peptidgerüst eine einzige Konformation bevorzugt. Aus der Temperaturabhängigkeit der chemischen Verschiebung der NH-Signale sowie deren Veränderung bei Zugabe von Chloroform wird auf nur ein intramolekular orientiertes Amidproton, nämlich das NH-Proton des Glycins, geschlossen. Die chemischen Verschiebungen der β- und γ-Prolinkohlenstoffe zeigen, daß beide Xaa - Pro-Amidbindungen cis-konfiguriert sind. Die Interpretation der Protonenabstände, ermittelt durch ein- und zweidimensionale NOE-Messungen, in Verbindung mit NH-CαH-Kopplungen läßt im Zusammenhang mit Modellbetrachtungen nur eine βII′-Konformation mit Phenylalanin in den Positionen (i + 1) und (i + 2) zu. Dieses Ergebnis steht im Gegensatz zu den bisher beobachteten Regelmäßigkeiten, denenzufolge wegen der L-Konfiguration beider Phe-Reste für 1 eine βI-Konformation zu erwarten wäre. Ungewöhnlich ist auch das Auftreten von zwei cis-Peptidbindungen in einem Pentapeptid.