Bibliothek

Notizen: The (12-20)-nonapeptide Z-Leu-Aib-Pro-Val-Aib-Aib-Glu (OBzl)-Gln-Pheol (10) of the ionophor alamethicin was synthesized by a new strategy, using 3-amino-2,2-dimethyl-2H-azirines 2 as synthons for the α-aminoisobutyric acid (Aib) moieties.

Notizen: Controlled ozonolysis of 2,3,5,6-tetramethylidene-7-oxabicyclo[2.2.1]heptane (1) afforded 3,5,6-trimethylidene-7-oxabicyclo[2.2.1]heptan-2-one (2). Ozonolysis of 2 gave a 1:1 mixture of 3,5-dimethylidene-7-oxa-bicyclo[2.2.1]heptane-2,6-dione (3) and 3,6-dimethylidene-7-oxabicyclo[2.2.1]heptane-2,5-dione (4). The He(Iα) photoelectron (PE) spectra of 2 and 4 have been recorded. Comparison with the PE data of related systems, and with the result of ab initio STO-3G calculations, confirm the existence of significant through-bond interactions between the oxygen lone-pair orbitals n(CO) of the carbonyl functions and n(O) of the O(7) ether bridge.

Notizen: The 1,2,3,4,4a,5,8,8a-octahydro-4β8aα-dimethylnaphthalen-4aβ-ol (= dehydrogeosmin; 1) has been identified as the olfactorily dominant compound in the flower scents of Rebutia marsoneri WERD., Dolichothele longimamma (DC.) BR. et R., and Sulcorebutia kruegeri (CARD.) RITT. The structure of 1, which might be of importance to the pollination biology of such Cactaceae, is based on spectral data and synthesis.

Notizen: The Cu2+ complex of 1, having a non-coordinating carboxylic group, can be reacted under the typical conditions of peptide formation with amines such as 2-methylpropylamine or (pyrid-2-yl)methylamine to give, after removal of Cu2+ with CN-, the amides 4 and 5. The Cu2+ ion is of paramount importance since it protects the four amino groups of the macrocycle so that the amide condensation can specifically be done with the exogenous amine It is also shown that the Cu2+ complex of 1 can be covalently attached to bovine serum albumin (BSA), thus opening the possibility to use this compound as a labelling agent for proteins and antibodies.

Notizen: Base treatment of azomalonates derived from N-substituted dialkyl (2-chloroacetamido)malonates results in the formation of 4-substituted alkyl 5-oxo-1,4,5,6-tetrahydro-1,2,4-triazine-3-carboxylates. The same malonates coupled with diazotized 2-amino-5-chlorobenzophenone or methyl anthranilate afford triazinones which can be cyclized into novel triazino[1,6-a]indoles. Two representative heterocycles are further characterized by typical reactions. Whereas oxidation gives the corresponding triazine-5,6-diones, the outcome of the reduction is strongly dependent on the nature of the substituent at C(4). Bromination followed by aqueous workup leads to the 6-hydroxy derivatives. Some mechanistic aspects of this novel triazinone synthesis are discussed.

Notizen: (3S,5R,6E,8E)-Deca-6,8-diene-1,3,5-triol, a New Metabolite from Streptomyces fimbriatus (MILLARD et BURR 1926)The title compound 2, a new C10-metabolite related to the previously found (3S-8E)-1,3-dihydroxydec-8-en-5-one (1), was isolated from the culture filtrate of Streptomyces fimbriatus, strain Tü 2335 by solvent extraction and chromatography. The constitution and the absolute configuration were determined by spectroscopic methods and chemical derivatization. The relative configurations were determined by NOE measurements with the silyl-protected 3,5-isopropylidene derivative of 2.

Notizen: A combined computational (MO ab initio) and structural-statistical study of molecules containing the O—C—N moiety is presented. Aminomethanol, the simplest member of this series, was computed using GAUSSIAN-82 with the 3-21G and 6-31G* basis sets and with complete geometry optimization, as well as with MP3//6-31G*. A set of carefully selected molecules containing the O—C—N unit was retrieved from the Cambridge Structural Database (CSD), and its structural parameters were analyzed according to an established procedure. Comparison between experimental and computational data was thus made possible. Results are consistent with the co-existence of two unequal anomeric effects in this system: a strong nN-σ*C—O anomeric interaction, and a weak nπO-σ*C—N one. The ability of the two basis sets to reproduce the energies and structural characteristics of the stereoelectronic effects is assessed, including the significance of using polarization functions and the inclusion of correlation energy.

Notizen: F430M, the pentamethyl ester of coenzyme F430, can be oxidized reversibly by one electron. The oxidation potential has been determined, and the electrolytically prepared oxidation product was characterized by its UV/VIS and ESR spectrum. The strongly anisotropic and nearly axial ESR spectrum is consistent with a S = ½ species with the unpaired-electron spin density predominantly in a dz2-type orbital of the central nickel ion. The properties of Ni(III)F430M are discussed in the context of two hypothetical mechanisms for the catalytic role of coenzyme F430 in methyl coenzyme M reductase, which catalyses the last step of methane formation in methanogenic bacteria.

Notizen: The η2-acyl complex [Fe(η2-EtC=O)I (CO)(PEt3)2] (1a) reacts with phenylacetylene in refluxing Et2O to form a mixture of products including [Fe(C(Ph)=CHC(O)Et}I(CO)(PEt3)2] (3), [Fe{C(Ph)=CHC(O)Et}1(CO)2(PEt3)2] (4), and [Fe{C(=CHPh)C(O)Et)I(CO)(PEt3)2] (5). Compound 3 contains a ‘metallafurane’ unit, while 5 consists of a 4-member metallacycle. Compound 5 was characterized by X-ray crystallography. In contrast to 1a, the η2-acyl complex [Fe{η2-(i-Pr)CO}I(CO)(PEt3)2] (1b) reacts with phenylacetylene under similar conditions to produce [Fe{η2-C(O)C(Ph)=CH(i-Pr)}I(CO)(PEt3)2 (7) which was characterized spectroscopically. Modified extended Hückel theory calculations were made on the model compounds [Fe(η2-CHO)(CO)2(PH3)2]+ (14), [Fe(CHO)(HCCH)(CO)2(PH3)2]+ (15), [Fe(=C=CH2)(CHO)(CO)2(PH3)2]+ (16), [Fe{C(=CH2)CHO}(CO)2(PH3)2]+ (17), and {Fe(CH=CHCHO)(CO)2(PH3)2]+ (18). The calculations show that in the transformation 15→18, there exists a transition state lying 83.6 kJ/mol above the optimized geometry of 15 in which the formyl unit is rotated by 80° with respect to the Fe-acetylene plane. Conversion of 15 to 17 involves a [1,2]-H shift and an acyl-acetylene coupling reaction which probably occur synchronously.

Notizen: The preparation of complexes [MX2(1)] (M = Ni, Pd, and Pi; X - Cl, Br, and I; 1 = 1,2-bis[(diphenylphosphino)methyl]benzene). [Pt(OSO2CH3)Et(1)], [Pt(alkene)(1)] (alkene - C2H2, and CH2 = CHCN), and [(1)Pt-(μ-H)2PtH(1)][BPh4] is reported. Their 1H- and 31P-NMR spectra were recorded and used lor structural assignments. The X-ray crystal structure of [Pt(C2H4)(1)] was determined. It is shown that the P—Pt—P bond angle in this complex differs significantly from those found in related compounds with monodentate phosphines, and that this difference is likely to be due to intramolecular contacts.

Notizen: As a direct test of the Cane-Westley hypothesis concerning the mode of assembly of ether rings in the polyether class of ionophore antibiotics, we describe experiments culminating in the synthesis of three putative intermediates on the monensin biosynthetic pathway and incorporation experiments with these materials and the monensin-producing organism Streptomyces cinnamonensis. The putative intermediates synthesised include the trienes [21-3H]-7 and [13-3H]-10, and the diene [9-3H]-11. The results of the incorporation experiments conducted with whole cell cultures suggest that [13-3H]-10 and [21-3H]-7 are unable to cross the intact cell membrane of S. cinnamonensis, whereas diene [9-3H]-11 can gain entry to the cellular interior, but is then degraded efficiently, most likely by a pathway closely related to β-oxidation, without being specifically incorporated into the antibiotic.

Notizen: The platinum(0) complexes [Pt(C2H4)(PP)] (PP = 1,2-bis[(diphenylphosphino)methyl]benzene (2) and (+)-DIOP = (+)-1,4-bis(diphenylphosphino)-1,4-dideoxy-2,3-O-isopropyliden-D-threitol), when promoted by CH3SO3H, become active catalysts for styrene hydroformylation with total yields of aldehydes ranging from 44 to 67% und selectivities towards 3-phenylpropanal ranging from 80 to 88%. Smaller amounts of the corresponding alcohols (3-18%) are also obtained with a selectivity towards 3-phenylpropanol of 94-96%. When DIOP complexes were used, no stereoselectivity for asymmetric hydroformylation was observed.

Notizen: The synthesis of 8-aza-1,3-dideaza-2′-deoxyadenosine (3a) as well as of 4- and 5,6-substituted benzotriazole 2′-deoxy-β-D-ribonucleosides is described (Schemes 1-3). Glycosylation of benzotriazole anions is stereoselective in all cases (exclusive β-D-anomer formation), but regioisomeric N1, N2, and N3-(2′-deoxyribofuranosides) are formed. The distribution of the regioisomers is controlled by the nucleobase substituents. Anomeric configuration as well as the position of glycosylation are determined by UV and NMR in combination with 1D-NOE-difference spectroscopy. The unprotonated forms of 4-aminobenzotriazoic 2′-deoxy-β-D-ribofuranosides 3a-c exhibit strong fluorescence.

Notizen: Regiospecific Synthesis of (Polyhydroxypropyl)-pterins: Synthesis of D-Anapterin and L-PrimapterinCondensation of 2,5,6-triaminopyrimidin-4-one(5) with the semicarbazone of pentoses proceeds regiospecifically with formation of 7-(polyhydroxypropyl)pterins. D-Anapterin (=7-(D-erythro-1′,2′,3′-trihydroxypropyl)pterin; D-3) was obtained in 40% yield, and L-primapterin (=7-(L-erythro-1′,2′-dihydroxypropyl)pterin; L-4)in 10% yield.

Notizen: Halochromic Molecules. Substituted 6,11-Dihydrospiro[[1]benzopyrano[4,3-b]indol-6,9′-9′H-xanthene]-2′,6′-diamines and Their Aza Analogues: New Chromogenes for Black Images.We have synthesized a series of substituted 6,11-dihydrospiro[[1]benzopyrano[4,3-b]indo1-6,9′-9′H-xanthene]-2′,6′-diamines and their respective aza analogues. These compounds develop a black colour in acidic media. The assumed structures of the analytically pure starting and final products are consistant with the fragmentations in the MS and are also supported by FT 1H-NMR. The UV/VIS spectra in buffered MeOH/H2O solutions were measured. From the ∊pH* curves, we determined the pK* values. The title compounds can be used in so-called pressure-sensitive copying systems.

Notizen: Reaction of 3-(Dimethylamino)-2H-azirines with 1,3-Oxazolidine-2-thione to 3-(2-Hydroxyethyl)-2- thiohydantoinsThe reaction of 3-(dimethylamino)-2H-azirines 1 and 1,3-oxazolidine-2-thione (6), in MeCN at room temperature, yields, after hydrolytic workup, 3-(2-hydroxyethyl)-2-thiohydantoins 7 (Scheme 2). In the case of the spirocyclic 1c, crystallization of the crude reaction mixture leads to spiro [cyclopentane-1, 7′(7′aH)-imidazo [4, 3-b] oxazole] -5′-thione 8c. The mechanism is discussed.

Notizen: Reaction of 3-(Dimethylamino)-2H-azirines with 1,3-Benzoxazole-2(3H)-thioneThe reaction of 3-(dimethylamino)-2H-azirines 2 with 1,3-benzoxazole-2(3H)-thione (5), which can be considered as NH-acidic heterocycle (pKaca. 7.3), in MeCN at room temperature, leads to 3-(2-hydroxyphenyl)-2-thiohydantoins 6 and thiourea derivatives of type 7 (Scheme 2). A reaction mechanism for the formation of the products via the crucial zwitterionic intermediate A′ is suggested. This intermediate was trapped by methylation with Mel and hydrolysis to give 9 (Scheme 4). Under normal reaction conditions, A′ undergoes a ring opening to B which is hydrolyzed during workup to yield 6 or rearranges to give the thiourea 7. A reasonable intermediate of the latter transformation is the isothiocyanate E (Scheme 3) which also could be trapped by morpholine. In i-PrOH at 55-65° 2a and 5 react to yield a mixture of 6a, 2-(isopropylthio)-1,3-benzoxazole (12), and the thioamide 13 (Scheme 5). A mechanism for the surprising alkylation of 5 via the intermediate 2-amino-2-alkoxyaziridine Fis proposed. Again via an aziridine, e.g. H (Scheme 6), the formation of 13 can be explained.

Notizen: The [4 + 2] cycloaddition stereoselectivity of dienamines 1-4 with dimethyl fumarate and fumaronitrile has been investigated, and functionalised decalins 21-40 have been prepared by elimination of Me2NH from cycloadducts 7-11 and 15-20; in the context of the synthesis of drimane sesquiterpenes, the reduction of dienediesters 29 and 30 is also described.

Notizen: Preparations of dimethyl (1RS,2SR,4RS,5SR,6SR,7RS)- and dimethyl (1 RS,2SR,4RS,5SR,6RS,7SR)-8-oxa-3-azatricyclo[3;2.1.024] octane-6,7-dicarboxylate 15 and18, resp.) and of their N-(tert-butyloxy)carbonyl (14, 17) and V-benzoyl (16, 19) derivatives are described. While treatment with nucleophilic acids (HCl, HBr. AcOH) of the exo, exo-diesters 14 and 16 gave the corresponding products 23-27 of aziridine trans -addition, the exo, endo -diesters 17 and 19 led to the corresponding amino-lactones 63 (methyl (1RS,2RS,3SR,6RS,7SR,9RS)-2-{[(tert-butyloxy)carbonyl] amino}-5-oxo-4,8-dioxatricyclo[4.2.1.0 37] nonane-9-carboxylate) and 64 (methyl (1RS,2RS,3SR,6RS,7SR,9SR)-2-(benzoylamino)-5-oxo-4,8-dioxatricyclo[4.2.1.0 3′7] (nonane-9-carboxylate). Under non-nucleophilic acidic conditions, the N-benzoylaziridine 16 was rearranged quantitatively into dimethyl (1RS,2SR,26SR,67SR,7SR,8SR,9SR)-4-phenyl-5,10-dioxa-3-azatricyclo[4.3.1.02′7] dec-3-ene-8,9-dicarboxylate(31), and 19 into dimethyl (1RS,2SR,26SR,67SR,7SR,8SR,9SR)-4-phenyl-3,10-dioxa-5-azatricyclo [5.2.1.02′6] dec-4-ene-8,9-di-carboxylate (65). Possible mechanisms of these highly selective reactions and rearrangements are discussed.

Notizen: Ozonolysis of the easily available monoterpenoids (-)-1 and (+)-1 leads in high yield to the ketoaldehydes (-)-4 and (+)-4, which serve as convenient intermediates for efficient new routes to both optical antipodes of the naturally occurring octenediol (E)-2 (Monarch butterfly secretion product) and octene-dicarboxylic acid (E)-3 (Callosobruchus chinensis sex pheromone). All steps proceed with almost complete retention of configuration, ensuring the synthesis of the target compounds with high optical purity.

Notizen: Novel tricyclic heterocycles were prepared and evaluated for their affinity to the central benzodiazepine receptor. The most potent compounds with IC50's in the nanomolar range were; found among thienoquinolizines and benzo[a]quinolizines (cf. Tables 2-5). The central ring of the tricyclic ring system may be partially unsaturated (cf. Tables 2 and 4) or fully unsaturated (cf. Tables 3 and 5) without loss of the high affinity to the receptor. The position of the ester group in the pyridinone ring is crucial for good binding (cf. Tables 1 and 2). It may be replaced by a broad variety of functional groups, e.g. amides, alkyl carbamates, alkyl groups, and hydroxyalkyl groups (cf. Tables 2-5). In the benzo[a]quinolizines, shifting the halogen atom from C(10) to C(9) leads to complete loss of affinity to the benzodiazepine receptor (cf. Table 4).

Notizen: Synthesis of 2,4-Diamino-thieno[2,3-d]pyrimidinesCondensation of 2-aminothiophene-3-carbonitrile (4) with guanidine or sequential addition of CS2 and NH3 to 4 provides 2,4-diaminothieno[2,3-d]pyrimidine (7). This compound yields, after sequential addition of sec-BuLi and either [3-(trifluoromethyl)benzene]sulfenyl chloride (8) or the corresponding disulfide 9, followed by acidic work up, 2,4-diamino-6-{[3-(trifluoromethyl)phenyl]thio}thieno[2,3-d]pyrimidine (10). In another approach, 2-amino-5-{[3-(trifluoromethyl)phenyl]thio}thiophene-3-carbonitrile (11) obtained from 4 and 8 is transformed to 10 by condensation with guanidine. Corresponding to the second route, 2,4-diamino-6-[(naphth-2-yl)thio]thieno-[2,3-d]pyrimidine (16) is synthesized. Oxidation of 10 with m-chloroperbenzoic acid gives 2,4-diamino-6-{[3-(tri-fluoromethyl)phenyl]sulfinyl}thieno[2,3-d]pyrimidine (13).

Notizen: Pteridines: Synthesis and Characteristics of 5,6-Dihydro-6-(1,2,3-trihydroxypropyl)pteridines: Covalent Intramolecular AdductsVarious 5,6-diaminopyrimidines (1, 15, 24, 33) were condensed with the phenylhydrazones of L-(2) and D-arabinose (3) in acidic medium under N2 to give formal 5,6-dihydro-6-(1,2,3-trihydroxypropyl)pteridines (see, e.g., 4 and 5), the latter turned out to exist preferentially as intramolecular adducts, the hexahydropyrano-[3,2-g]pteridines 6, 7, 16, 17, 25, 26, and 34, formed subsequently by addition of the terminal OH group of the side-chain to the C(7)=N(8) bond of the pteridine moiety. Spectroscopically, the isomeric hexahydrofuro-[3,2-g]pteridines 10,11,18,19, and 35 were also detected as minor components in the equilibrium mixtures. In the 4-amino-2-(methylthio)pteridine series, crystallization of 6 and 7 led to the stereochemically pure (3S,4R,4aR, 10aS)-6-amino-3,4,4a,5,10,10a-hexahydro-8-(methylthio)-2H-pyrano[3,2-g]pteridine-3,4-diol (8) and its corresponding enantiomer 9, respectively Structure 8 was proven by X-ray analysis. Acylation of the hexahydropyrano[3,2-g]pteridines yielded the more stable tri-, tetra-, and pentaacetyl derivatives 12-14, 20-23, 27-32, and 37-39 which were characterized and of which the absolute and relative configurations were determined (1H- and 13C-NMR and UV spectra, chiroptical measurements, elemental analyses).

Notizen: Starting from the readily available, optically active (4R)-4-hydroxy-2,2,6-trimethylcyclohexanone (1), a new technical synthesis of (3R,3′R)-zeaxanthin is described. According to a 2(C9 + C6) + C10 = C40 construction scheme, the ketone 1 was first transformed with (E)-3-methylpent-2-en-4-yn-1-ol (5) into a C15-intermediate which, by a three-step sequence, could be converted into the known olefinic C15-Wittig salt 4. Optimized conditions for the final Wittig reaction of 4 with the C10-dialdehyde 3 are discussed. Based on 1, the overall yield of the entire technical process is ca. 40%.

Notizen: Two new 20(10→5)abeo-abietune diterpenoids, pygmaeooins B (1) and C (2), have been isolated from the roots of Pygmaeopremna herbacea (Verbenaceae). Their structures were elucidated on the basis of spectroscopic data, and chemically, both compounds were correlated with each other. The absolute configurations were assigned tentatively on the basis of biogenetic pathway.

Notizen: The 12H-dibenzo [d, g] dioxathiocines 2 and 4 are prepared by condensation of the corresponding bis[phenols] 1 and 3 with SOCl2 and SCl2, respectively. X-Ray analysis reveals the presence of the boat-chair (BC) form as the only conformer in the solid state of the cyclic thiodioxy derivative 4a, whereas the sulfinyldioxy compound 2a exists in the asymmetric axial boat (B) form, i. e. with endo (axial) orientation of the exocyclic O-atom. Conformational analysis using 1H-NMR spectroscopy indicates the presence of a boat form for compounds 2, whereas compounds 4 again exist in the boat chair form. A comparison of 1H-NMR and thermodynamic parameters with those of the cyclic sulfinyldioxy compound 5 with an equilibrium between e-BC and a-BC form (i.e. BC form with equatorial and axial orientation of the exocyclic O-atom) is made.

Notizen: The hydrogenations of methyl 2-oxoeyclopentanecarboxylate (1), ethyl 2-oxocyelohexanecarboxylate (3), and 2-methylcyclohexanone (5) on unmodified Raney-Ni catalyst lead predominately to the formation of the cis-hydroxy diastereoisomers of 2, 4, and 6, respectively (Scheme 2). In the asymmetric hydrogenations on catalysts modified with chiral tartaric acid ((R, R )-C4H6O6/Raney-Ni and (R, R)-C4H6O6/NaBr/Raney-Ni), the predominance of the cis-isomer increases significantly. The hydrogenations of β-keto esters 1 and 3 proceed with an enantioselectivity of 10-15% on the modified catalysts, while the similar hydrogenation of 5 yields optically inactive 6. The (1S,2R)-enantiomers of the cis-isomers of 2 and 4 are formed in larger quantity, whereas the (lR,2R)-enantiomers of the corresponding trans-isomers predominate (Scheme 1). The enantioselective formation of trans-2 and trans-4 can be interpreted mainly in terms of the asymmetric hydrogenation of cyclic β-keto esters through the keto form, while that of the corresponding cis-hydroxy esters proceeds through the enol form.

Notizen: Chloro(cyclopentadienyl)bis(1,2:5,6-di-O-isopropylidene-α-D-glucofuranos-3-O-yl)titanium (1) is used for the transmetallation of Li-enolates obtained from propionyl derivatives. While such Ti-enolates of ketones and hydrazones appear to be unreactive, the (E)enolate 13 of 2,6-dimethylphenyl propionate (11) adds to the re-side of aldehydes, affording various syn-aldols 14 with high dia- and enantioselectivity (92-97% ds, 91-97% ee, cf. Scheme 2 and Table 1). Racemic syn-aldols (±)-14 are obtained analogously from the achiral bis(2-propyloxy)-Ti-enolate 15 (Scheme 2 and Table 2). In contrast to the unstable Li-enolate 10, the Ti-enolates 13 and 15 isomerize at -30°, presumably to the thermodynamically more stable (Z)-enolates (Scheme 4), While the diastereoselectivity of the achiral enolate 15 is lost upon this equilibration, the chiral (Z)-enolate 27 quite unexpectedly affords anti-aldols 12 of high optical purity (94-98% ec) and, in most cases, with acceptable-to-good diastereoselectivity (82-90% ds). Notable exceptions are branched unsaturated and aromatic aldehydes which form a greater proportion of synepimers of moderate optical purity (Scheme 5 and Table 3). Consistent with these findings, re-facial-and ami -selective aldol-addition is also exhibited by the (Z)-configurated Ti-enolate 22 of N-propionyl-oxazolidi-none 19 (Scheme 3).

Notizen: Synthesis of Optically Pure Grasshopper Ketone and of Its Diastereoisomers and Related CompoundsStarting from our previously described synthon 1, the synthesis of four enantiomerically pure grasshopper ketons (diastereoisomeric 4-(2′,4′-dihydroxy-2′,6′,6′-trimethylcyclohexylidene)but-3-en-2-ons) and of their oxo derivatives was performed. Spectral and chiroptical data are presented.

Notizen: Novel cationic allylpalladium (II) comp, exes containing the alkaloid (-)sparteine (1) as a bidentate ligand have been prepared. Two of them, [η3(cyclohex-2-enyl)] (sparteine)palladium(II) hexafluorophosphate([Pd(η3-C6 H9)(sparteine)][PF6] 3b) and (sparteine)[η3-(1,1,3-triphenylallyl)] palladium (II) trifluorophosphate ([Pd(η3-Ph2CCHCHPh)(sparteine)][sparteine)] [CF3SO3]; (3c) were characterized by X-ray diffraction. The application of 2D-NMR methods (COSY and NOESY)affords a correlation between the solid-state and solution structures for complex 3c.

Notizen: Chiral [2H] -labelled methylene groups flanked by two double bonds within (poly)unsaturated fatty acids are readily available from trans-2,3-epoxy[2,3-2H2] alk-4-yn-l-ols, obtained in their turn by asymmetric epoxidation of the corresponding (E)-[2,3-2H2] alk-2-en-4-yn-l-ols (see Scheme 3). The procedure is exemplified for (8S,3Z,6Z,9Z)-[7,8-2H2] trideca-3,6,9-trienoic acid ((8S)-11) and (8R)-11 (Scheme 4) as well as for (5S,3Z,6Z)-[4,5-2H2]deca-3,6-dienoic acid ((5S)-13) and (5R)-13 (Scheme 5).

Notizen: Separation and Quantitation of All Eight Stereoisomers of α-Tocopherol by ChromatographyThe results of the analysis of several derivatives of (all-rac)-α-tocopherol by HPLC on a chiral stationary phase and by capillary GC on a achiral stationary phase are reported. Consecutive application of both methods to the ethyl-ether derivative allows the separation and quantification of all eight possible stereoisomers of (all-rac)-α-tocopherol.

Notizen: The Mediterranean alcyonacean Alcyonium ( = Parerythropodium) coralloides (Pallas, 1766) is shown here to contain coralloidolide F ( = (+)-(3a-R*, 7R*, 8R*, 9R*, 12R*, 12aS*)-8,9-epoxy-1,3a,6,7,8,9,10,11,12,12a-decahydro-3a-hydroxy-12-isopropenyl-2,5-dimethyl-1-oxocyclopfintacycloundecene-9,7-carbolactone; (+)-2), the first example of a 2,6-cyclized cembranolide. Structural assignments are mainly based on ID and 2D NMR and MS data.

Notizen: Cyclohex-2-enones 1a-1c undergo photocycloaddition to tetramethoxyethylene in benzene to afford 1-oxa-spiro[3.5]non-5-enes 3 in very good yields. In MeCN as solvent, higher relative amounts of bicyclo[4.2.0]octan-2-ones 4 are formed. Results from similar experiments with the same enones and 2,3-dimethylbut-2-ene or 1,1-dimethoxyethene indicate that the driving force for oxetane formation is a sufficiently large difference in redox potentials between Ered of the enone and Eox of the alkene. A mechanism is proposed for cycloalk-2-enone + alkene photocycloadditions wherein the cyclobutane adducts arise from an exciplex intermediate and the oxetanes from a subsequently formed contact ion-pair.

Notizen: The Synthesis of Some 2H-Pyran-2-one DerivativesDerivatives of 6-unsubstituted 2H-pyran-2-one have been synthesized by several different methods. The 4-chloro-2H-pyran-2-one (9) is the most important, since it serves as starting material for the synthesis of different 4-substituted 2H-pyran-2-ones (Scheme 2). Also described are simple transformations of cumalic-acid derivatives producing 5-(2,2-dichlorovinyl)-2H-pyran-2-one (23), 2-oxo-2H-pyran-2-carbonitrile (26), and 4,5-bis(trifluoromethyl)-2H-pyran-2-one (32) (Scheme 3 and 4).

Notizen: (±)-Muscone ((±)-1) has been synthesised in three steps from 2-(2′-methylprop-2′-enyl)cyclododecan-1-one (2). The synthesis involves two key transformations: a Lewis-acid-mediated intramolecular ene reaction (2→3) and the β-cleavage of the bicyclic potassium alkoxide 3a′ to the macrocyclic enone (Z)-11.

Notizen: The thermal and hydrolytic degradation of tetrahydrolipstatin (THL, 1) was investigated. All main degradation products were isolated, characterized, and synthesized. Labile intermediates unavailable to isolation were detected and identified by GC/MS analysis of their silylated derivatives, and whenever possible, compared with independently prepared reference compounds. The identified degradation products represent at least 97% of the total degradation mixture. Two main reaction pathways arc proposed. Pharmacological data are reported for the degradation mixture and the main degradation products.

Notizen: Natural primapterin (80 μg) was isolated from 200 ml of urine of a patient with mild hyperphenylalaninemia. The CD curve of the compound showed that it belongs to the L-series of 7-(polyhydroxypropyl)pterins.

Notizen: A New Method for the Stereochemical Analysis of Acyclic Terpenoid Carbonyl CompoundsA new method for the determination of the enantiomeric and diastereoisomeric composition of terpenoid carbonyl compounds is presented. Separation of the diastereoisomeric (+)-L-diisopropyl-tartrate acetals derived from dihydrocitronellal (6), hexahydropseudoionone (3), hexahydrofarnesal (7), and hexahydro far nesy lace tone (4), the C10, C13, C15, and C18 intermediates in various syntheses of naturally occurring tocopherols and vitamin K1, can be achieved by capillary GC on a cyanopropylsilicon-coated glass column under standardized conditions. This technique, presenting a significant improvement over existing methodologies, is considered to be particularly useful for the analysis of highly enriched samples, typically obtained by present-day asymmetric synthesis. With reproducibilities of ± 0.3%, and, therefore, safe for routine analysis, the complete Stereochemical characterization of terpenoids with 15 and 18 C-atoms bearing two stereogenic centres is performed in a single operation for the first time.

Notizen: Synthetic procedures have been developed for the preparation of ligands bearing two to six pendent, unsubstituted or substituted 2, 2′-bipyridine groups attached to acyclic (tripode, tetrapode) and macrocyclic (triazanonade-cane, cyclam, hexacyclen, bis(bipyrido)hexaazamacrocycle) polyamines. Ligands 1-5 have been obtained in high yield by condensation of 6-(bromomethyl)-2, 2′-bipyridine (9b) with the corresponding amines in the presence of NaOH, H2O, and MeOH. Ligands 6-8 have been prepared in good yield by condensation of 9b or the di- or tetrasubstituted mono (bromomethyl) bipyridine 10b or 11b, respectively, with the corresponding amines in the presence of Na2CO3 and MeCN. Ligand 1 forms hemi-cage complexes with RuII, FeI, CrII, and CrIII cations and trinuclear complexes with [RuCl2(bpy)2] and [ReCl(CO)5]. Tetrapode 2 and hexapode 4 gave tetranuclear and dinuclear complexes, respectively, by reaction with Fe11 salts. These complexes possess a variety of interesting physical and chemical properties.

Notizen: The recently developed general principle of ion-selective optode membranes, based on conventional ionophores, was employed to design a new approach to the determination of enantiomeric excess. Highly lipophilic chiral crown derivatives, exhibiting a high selectivity for a chiral ammonium guest cation, are combined with a H+-selective chromoionophore in a plasticized PVC membrane. The enantiomer recognition process is translated by this sensor with an optical transduction into a signal easily measured by a conventional spectrophotometer, and enantiomeric excess can be determined without the need for polarized light. Characteristics and a theoretical description of these new optode membranes are given.

Notizen: ‘tert-Amino Effect’ on Acidic Treatment of (Pyrrolidin-l-yl)azadienesThe behaviour of 4-morpholino- and 4-(pyrrolidin-l-yl)-2-aza-1. 3-diene-l, l-dicarbonitriles 3, and 4 and 10, respectively, in acidic medium is described. The former gives with HBr/AcOH 3-bromopyrazine-2-carbonitrile 6. On the other hand, pyrrolidin-1-yl derivatives 4 and 10 furnish, by a [1, 5]-H shift, pyrrolo[l, 2]pyrazine structures 5 and 11, respectively.

Notizen: The convergent syntheses of 3-deazapurine 2′-deoxy-β-D-ribonucleosides and 2′,3′-dideoxy-D-ribonucleosides, including 3-deaza-2′-deoxyadenosine (1a) and 3-deaza-2′,3′-dideoxyadenosine (1b) is described. The 4-chloro-lH-imidazo[4,5-c]pyridinyl anion derived from 5 was reacted with either 2′-deoxyhalogenose 6 or 2′,3′-dideoxyhalogenose 10 yielding two regioisomeric (N1 and N3) glycosylation products. They were deprotected and converted into 4-substituted imidazo[4,5-c]pyridine 2′-deoxy-β-D-ribonucleosides and 2′,3′-dideoxy-D-ribonucleosides. Compounds 1a and 1b proved to be more stable against proton-catalyzed N-glycosylic bond hydrolysis than the parent purine nucleosides and were not deaminated by adenosine deaminase.

Notizen: The acid-catalyzed rearrangement of N-(1′,1′-dimethylprop-2′-ynyl)-, N-(1′-methylprop-2′-ynyl)-, and N-(1′-arylprop-2′-ynyl)-2,6-, 2,4,6-, 2,3,5,6-, and 2,3,4,5,6-substituted anilines in mixtures of 1N aqueous H2SO4 and ROH such as EtOH, PrOH, BuOH etc., or in CDCl3 or CCl4 in the presence of 4 to 9 mol-equiv. trifluoroacetic acid (TFA)has been investigated (cf. Scheme 12-25 and Tables 6 and 7). The rearrangement of N-(3′-X-1′,1′-dimethyl-prop-2′-ynyl)-2,6- and 2,4,6-trimethylanilines (X = Cl, Br, I) in CDCl3/TFA occurs already at 20° with τ1/2 of ca. 1 to 5 h to yield the corresponding 6-(1-X-3′-methylbuta-1,2′-dienyl)-2,6-dimethyl- or 2,4,6-trimethylcyclohexa-2,4-dien-1-iminium ions (cf. Scheme 13 and Footnotes 26 and 34) When the 4 position is not substituted, a consecutive [3,3]-sigmatropic rearrangement takes place to yield 2,6-dimethyl-4-(3′-X-1′,1′-dimethylprop-2′-ynyl)anilines (cf. Footnotes 26 and 34). A comparable behavior is exhibited by N-(3′-chloro-1′-phenylprop-2′-ynyl)-2,6-dimethylaniline (45., cf. Table 7). The acid-catalyzed rearrangement of the anilines with a Cl substituent at C(3′) in 1N aqueous H2SO4/ROH at 85-95°, in addition, leads to the formation of 7-chlorotricyclo[3.2.1.02,7]oct-3-en-8-ones as the result of an intramolecular Diels-Alder reaction of the primarily formed iminium ions followed by hydrolysis of the iminium function (or vice versa; cf. Schemes 13,23, and 25 as well as Table 7). When there is no X substituent at C(1′) of the iminium-ion intermediate, a [1,2]-sigmatropic shift of the allenyl moiety at C(6) occurs in competition to the [3,3]-sigmatropic rearrangement to yield the corresponding 3-allenyl-substituted anilines (cf. Schemes 12,14-18, and 20 as well as Tables 6 and 7). The rearrangement of (-)-(S)-N-(1′-phenylprop-2′-ynyl)-2,6-dimethylaniline ((-)-38; cf. Table 7) in a mixture of 1N H2SO4/PrOH at 86° leads to the formation of (-)-(R)-3-(3′-phenylpropa-1′,2′-dienyl)-2,6-dimethylaniline ((-)-91), (+)-(E)- and (-)-(Z)-6-benzylidene-1,5-dimethyltricyclo[3.2.1.02′7]oct-3-en-8-one ((+)-(E)- and (-)-(Z)-92, respectively), and (-)-(S)-2,6-dimethyl-4-( 1′-phenylprop-2′-ynyl)aniline((-)-93). Recovered starting material (10%) showed a loss of 18% of its original optical purity. On the other hand, (+)-(E)- and (-)-(Z)-92 showed the same optical purity as (minus;)-38, as expected for intramolecular concerted processes. The CD of (+)-(E)- and (-)-(Z)-92 clearly showed that their tricyclic skeletons possess enantiomorphic structures (cf. Fig. 1). Similar results were obtained from the acid-catalyzed rearrangement of (-)-(S)-N-(3′-chloro-1′phenylprop-2′-ynyl)-2,6-dimethylaniline ((-)-45; cf. Table 7). The recovered starting material exhibited in this case a loss of 48% of its original optical purity, showing that the Cl substituent favors the heterolytic cleavage of the N-C(1′) bond in (-)-45. A still higher degree (78%) of loss of optical activity of the starting aniline was observed in the acid-catalyzed rearrangement of (-)-(S)-2,6-dimethyl-N-[1′-(p-tolyl)prop-2′-ynyl]aniline ((-)-42; cf. Scheme 25). N-[1′-(p-anisyl)prop-2-ynyl]-2,4,6-trimethylaniline(43; cf. Scheme 25) underwent no acid-catalyzed [3,3]-sigmatropic rearrangement at all. The acid-catalyzed rearrangement of N-(1′,1′-dimethylprop-2′-ynyl)aniline (25; cf. Scheme 10) in 1N H2SO4/BuOH at 100° led to no product formation due to the sensitivity of the expected product 53 against the reaction conditions. On the other hand, the acid-catalyzed rearrangement of the corresponding 3′-Cl derivative at 130° in aqueous H2SO4 in ethylene glycol led to the formation of 1,2,3,4-tetrahydro-2,2-dimethylquinolin-4-on (54; cf. Scheme 10), the hydrolysis product of the expected 4-chloro-1,2-dihydro-2,2-dimethylquinoline (56). Similarly, the acid-catalyzed rearrangement of N-(3′-bromo-1′-methylprop-2′-ynyl)-2,6-diisopropylaniline (37; cf. Scheme 21) yielded, by loss of one i-Pr group, 1,2,3,4-tetrahydro-8-isopropyl-2-methylquinolin-4-one (59).

Notizen: Fluorescence measurements have been used to follow the build-up of photoproducts during the direct and benzophenone-sensitized irradiation of the title compounds 1-IN, 1-BrN, and 1-ClN (HN = naphthalene). Compounds 1-IN and 1-BrN react by homolytic dissociation through their lowest triplet and singlet excited states, respectively. Compound 1-ClN does not undergo C-Cl bond fission, except through electron transfer in the presence of an amine A, In the absence of this electron transfer, 1-ClN reacts only through substitution and oxidation processes.

Notizen: Thermolysis of Heterocyclic Azidinium TetrafluoroboratesThe thermolysis of some azidinium salts was investigated. It led to a large variety of products which were isolated or identified by GC/MS. Reaction mechanisms are discussed to explain the product formation.

Notizen: Reduction of indolin-2-ones with lithium aluminium hydride (LAH) or diisobutylaluminum hydride (DIBAL) and desulfurization of indoline-2-thiones with Raney-Ni were investigated. Treatment of indoline-2-ones 1 with LAH or DIBAL yield indoles 4 and/or indolines 3 in moderate-to high yield depending on the substituents at N and C(3) of 1. Indoline-2-thiones 2 were desulfurized with Raney-Ni to give indoles 4 and/or indolines 3.

Notizen: 14-Methoxymetopon (= 5,14-O-dimethyloxymorphone; 4)and 14-ethoxymetopon (5) were synthesized from 14-hydroxy-5-methylcodeinone (6). In the AcOH-writhing test in mice, compound 4 was found to be ca. 20000 times more potent than morphine.

Notizen: A new versatile and efficient regio-, diastereo-, and enantioselective synthesis of vicinal diols s-trans-4, s-trans-5, and s-cis-4 is described. Symmetrical ketones are converted into their SAMP-or RAMP-hydrazones which are then silylated with (isopropyloxy)dimethylsilyl chloride, followed by ozonolysis to afford the α-silyl ketones (R)-2 of high enantiomeric purity (ee 90- ≥ 98%). On the other hand, methyl ketones, after conversion into the corresponding (-)-(S)-1-amino-2-(methoxymethyl) pyrrolidine (SAMP) hydrazones, are silylated and then alkylated with RI to afford unsymmetrical α-silyl ketones (S)-3 of high enantiomeric purity (ee 90- ≥ 98%). The reduction of the above obtained α-silyl ketones with L-Selectride, followed by oxidative cleavage of the C—Si bond gives rise to s-trans-4, s-trans-5, and s-cis-4 with high diastereoselectivity (de 95- ≥ 98%) and without racemization (ee ≥ 90- ≥ 98%).

Notizen: The absolute configuration of the 2-(phenylmethyl)pyridine derivatives 1-9 had been established by X-ray diffraction and chemical correlation. Their CD spectra have been studied in different solvents for the free and protonated forms. It has now been found that, from the sign of the strong CD couplet between 270 and 220 nm, which was observable for all these compounds besides 7 and 9, their absolute configuration can be determined much quicker.

Notizen: Further Contributions to the Synthesis of (+)-AspicilinThere are two reasons to try to find out. whether the initial and final parts of the ‘photochemical synthesis’ of the 18-membered lichen macrolide (+)-aspicilin (5a) can be improved (cf. Schemes 1 and 2). This synthesis acts as an indicator for the utility of the earlier introduced photolactonization and as a source of large-ring-sized lactones, objects for computer-assisted conformational analysis.

Notizen: Continuing studies of the global extracts from cultures of the marine deuteromycete Dendryphiella salina have led to the isolation of novel compounds that add to the scarce list of marine fungal metabolites. Besides (22E)-ergosta-4.6,8(14),22-tetraen-3-one which, though known from basidiomycetes, was unknown in the sea, they are an unusual glyceryl ester, i.e. glycer-1-yl dendryphiellale A (= (+)-(2R)-2,3-dihydroxyprop-l-yl (6S,2E,4E)6-methylocta-2,4-dienoate; (+)-1), a trinor-eremophilane, i.e. dendryphiellin A1 ( = (+)-(3R*,4E,6E)-7-{[(1R*,2S*,7R*,8aR*)-1,2,6,7,8,8a-hexahydro-7-hydroxy-1,8a-dimethyl-6-oxonaphthalen-2yl]oxycarbonyl}-3-methylhepta-4,6-dienoic acid; (+)-11), and two eremophilanes, i.e. dendryphiellin El ( = (+)-(1R*, 2S*, 7S*,8aR*)-1,2,6,7,8,8a-hexahydro-1,8a-dimethyl-7-(1-methylethenyl)-6-oxonaphthalen-2-yl(6S,2E,4E)-6-methyl-octa-2,4-dienoate; (+)-13) and dendryphiellin E2 ( = (+)-(1R*, 2S*, 8aR*)-1,2,6,7,8,8a-hexahydro-7-isopropyl-idene-1,8a-dimethyl-6-oxonaphthalen-2-yl (6S,2E,4E)-6-Methylocta-2,4-dienoate; (+)-14). Absolute configurations have been established for (+)-1 via total synthesis and for the acid portion of (+)-13 and (+)-14 via transesterification in NaOMe/MeOH which gave in both cases melhyl dendryphiellate A ((+)-16) of known configuration and the free alcoholic moiety of (+)-14, i.e. (+)-17.

Notizen: Stereoselective Syntheses of Substituted Tricarbonyl[tris(methylen)methan]iron(0) ComplexesThe complexes 3, 9, 10, 22, and 23 with one, two, and three Me substituents at the tris(methylen)methane moiety have been synthesized from the (acyloxy-1,3-diene)(tricarbonyl)iron(0) complexes 1, 4, 5, 20, and 21, respectively, by ionic hydrogenation with BF3 and Et3SiH at -78° in CH2C12. These reductions are completely stereoselective, and their course can be predicted by assuming a dominant stereoelectronic control of the reaction. Formation of the carbocationic intermediates 11 from 4 and 12 from 5, e.g., takes place only if the dissociating O—C bond is antiperiplanar to the donor C(β)—Fe bond. Fast H-transfer then converts the intermediate 11 to 9 and 12 to 10. The configurations of 17 and 20 can be deduced from the structure of 22 and those of 18 and 21 from that of 23. An X-ray structure determination of (1R,4S)camphanoate (-)-13 derived from alcohol (-)-7 confirms the configuration of 5 deduced above, The structures of the complexes 9 and 10, 22 and 23 were determined by their unique NMR spectra. The diastereoisomeric complexes 6 and 7 have been synthesized from aldehyde 8 with MeMgI, the diastereoisomers 17 and 18 analogously from 16 or from methyl ketone 19 by reduction with LiAlH4. Optically active starting materials (+)-1, (-)-13, (+)-20, and (+)-21 gave, by ionic hydrogenation, the complexes (-)-(3R)-3, (+)-(2S,4S)-10, (-)-(R,R, S)-22, and (-)-(R,R,R)-23 respectively, with known absolute configurations.

Notizen: Using extended Hückel wave functions, molecular electrostatic potentials (MEP's) have been calculated for several model clusters representative of zeolites of offretite type. The clusters studied, which are all made of a central unit comprising 2 AlO4 and 16 SiO4 tetrahedra, differ only by the relative positions of the Al-atoms occupying the same crystallographic sites (T2) within the zeolite framework. using the MEP values as a color-coded acidity index for the various clusters, three-dimensional representations of their molecular surfaces are generated as solid models on a performing computer graphics system. Important differences in acidity are predicted for the clusters which can he classified into two types according to the distribution of Al-atoms: the first one is characterized by nearly independent acid sites localized around the main channel of zeolite (Figs. 3 and 6) whereas the second one exhibits interacting acid sites located longitudinally along the channel of the same gmelinite cage (Figs. 4 and 5). The possible relationship between the structure of the clusters and their catalytic activity towards organic species is discussed.

Notizen: Starting from D-glutamic acid (5), the bicyclic compounds 4a and 4b were synthesized via 17 (Schemes 1 and 2). The reaction leading to 4g and 4h with LiCuPh2 was not successful. But treatment of the N-protected model lactams 19, 21, and 22 with Li2Cu(CN)Ph2 gave the amino ketones 24, 26, and 27, respectively (Scheme 3). The desired compound 23 was obtained from 20. Conversion of the unprotected lactams 28, 31, and 32 gave the phenyl derivative 34 in excellent yields. Ester 35 was transformed to the α -amino-γ- oxo-acid derivative 36. This conversion opens a novel access to this type of compounds.

Notizen: Bare Fe(I) cations act in the gas phase as dehydrosulfurization catalysts for butyl isothiocyanate by specifically coupling the S-atom with remote H-atoms from the ω and (ω - l) position of the alkyl chain. Other losses induced by Fe(I) are due to ‘remote functionalization’, the formation of ion/dipole intermediates, and insertion/β-hydrogen shift processes.

Notizen: Syntheses and Chemical Properties of Heterocyclic Tetracyanodimethanes of a Heterocyclic N,N′-Dicyanodiimine and of Fully Substituted Monocyclic TetracyanodimethanesIn the presence of different bases, 4,8-diethoxy-3H,7H-benzo[1,2-c:4,5-c′]diisoxazole-3,7-dione (3) reacts with malonodinitrile or β-oxobenzenepropanenitrile to the coloured salts 4a,b and 5, respectively, which are alkylated to the tetracyanoquinodimethane-like heterocycles 2a,b and to the bis [benzoyl(cyano)methylidene]-substituted heterocycle 6 (Scheme 1). Hydrogenation of 2a,b affords the fully substituted 7a,b, and with 2-(1,3-dithiol-2-ylidene)-1,3-dithiole, 2a gives the 1:1 charge-transfer complex 8. Heterocyclic quinone 9 is transformed to the monocyarioimino derivative 10, and 3 reacts with cyanamide and NaH to the N,N′-dicyanodiimine salt 12.

Notizen: The ability of the monensin-producing organism Streptomyces cinnamonensis to bioconvert the (E)-and (Z)-isomers of nerolidol (= 3,7,1 1-trimethyldodeca-1,6,10-trien-3-ol) into new oxygenated products has been investigated. When a 3H-labelled racemic form of each sesquiterpene was added to fermentations of S. cinnamonensis, several new 3H-labelled products could be detected. Two products were isolated from bioconversion of (E)-nerolidol, the amide 8 and the 9 (Scheme 2), whereas four products were isolated from the bioconversion of (Z)-nerolidol, the epoxydiol 10, triols 11 and 12, and the tetrahydrofuryl alcohol 13 (Scheme 4). Products 9-13 were obtained as a 1 : 1 mixture of diastereoisomers, and 12 was shown to arise by the overall anti addition of two OH groups to the trisubstituted (Z)-double bond of (Z)-nerolidol. Both isomers of nerolidol as well as the acetylene 7 are inhibitors of monensin production in shake cultures of S. cinnamonensis.

Notizen: It is shown that the nudibranch mollusc Armina maculata and its prey, the pennatulacean octocoral Veretillum cynomorium, of east Pyrenean waters contain a novel cembranoid, preverecynarmin ((+)-8), besides the known cembranoid cembrene C (9) and three further briarane diterpenoids (verecynarmin E ((-)-5), F ((-)-6), and G ((-)-7)). A biogenetic scheme is proposed.

Notizen: Biomimetic syntheses of racemic aristomakinine ((±)-3) and aristomakine ((±)-4), an unusual indole alkaloid bearing an N-isopropyl group, are described. The key step is a Grob-type fragmentation of anti-15-aristotelinyl methanesulfonate ((±)-2) to the intermediate iminium ion I which, upon subsequent hydrolysis, furnished aristomakinine ((±)-3). On the other hand, the same intermediate could be reduced in situ to aristomakine ((±)-4). The controversial relative configurations of the two alkaloids have been firmly established by means of NOE difference experiments.

Notizen: Synthesis of two naturally occurring macrocyclic lactones is described. (-)-(R)-Phoracantholide I ((-)-1; Scheme 2) was synthesized by asymmetric and chemoselective reduction of the side-chain C=O group of (-)4-(1-nitro-2-oxocyclohexyl)butan-2-one ((-)-6) with (R)-Alpine-Hydride (47% ee). It was shown that the formation of only one diastereoisomer of the hemiacetal 5, by methylation with (i-PrO)2TiMe2 of ketoaldehyde (-)-2 is thermodynamically controlled. (+)-(S)-Tetradecan-13-olide ((+)-10) was obtained by reduction of diketone (±)-11 with optically active borohydrides followed by denitration (Scheme 3).

Notizen: The synthesis of 2,2-bis(hydroxymethyl)-4-methyl-5-phenylfuran-3(2H)-one (9), 5-[(1S,2S,Z)-1,2-(ethylidenedioxy)hex-3-enyl]-2,2-bis(hydroxymethyl)-4-methylfuran-3(2H)-one (24), and 5-[(1S,2S,Z)-1,2-(ethylidenedioxy)hex-3-enyl]-2-(hydroxymethyl)-4-methylfuran-3(2H)-one (28), which represent more advanced, suitably functionalized intermediates for the synthesis of pseurotin A (1), a secondary metabolite of Pseudeurotium ovalis STOLK, is described.

Notizen: The absorption band maximum of solvated electrons, λmax(e-s), in 3- or 4-methylcyclohexanols is observed at longer wavelengths (818-837 nm), if the OH group is axial, and at shorter wavelengths (721-723 nm), if it is equatorial. It is surmised that the size of cavity for the solvated electron is larger in the former case and smaller in the latter.

Notizen: Boscialin (1), a new compound structurally related to the ionones and abscisic acid, and its 4′-O-glucoside 2 were isolated from the MeOH extract of the leaves of the African medicinal plant Boscia salicifolia. The structures of the two compounds were determined mainly by NMR spectroscopy and by acid hydrolysis of the glycoside.

Notizen: Energy profiles for nitrogen inversion in ammonia (1), aziridine (2), 1 H-azirine (3), trans-2,3-difluoro-aziridine (4), cis-2,3-difluoroaziridine (5), 2,3-difluoro-1H-azirine (6), methanimine (7), and 2,2-difluoro-methammine (8) have been calculated at the 6-31 G** and 4-21G* levels. If the reaction coordinate is chosen as the angle τ between the N—H bond and the C—N—C plane (or the N—C line for the imines 7 and 8), the energy is reproduced quite well by a quartic function V(τ) = aτ4 - bτ2 in all cases. Moreover, for this series of molecules the ratio a/b is approximately constant, which means that the inversion barrier is directly proportional to the quadratic force constant of the equilibrium structure along the reaction coordinate. The use of this and other simple relationships for automerization reactions is discussed. Some of the molecules studied show features that can be nicely interpreted in terms of stereoelectronic factors.

Notizen: Structure of the Valenciaxanthins and ValenciachromesValenciaxanthin, a carotenoid first isolated from Californian Valencia orange juice in 1952/1954 by American scientists, was re-isolated from fresh Spanish ‘Navelinas’ and shown, by spectroscopical and chiroptical examination, to have the unexpected (9Z)-10′-apo-11′,12′-dihydroviolaxantin-10′-ol structure 6. A further, very minor component represents the (all-E)-structure 7. Therefore, the Valenciachromes are the furanoid rearrangement products of 6 and 7 and, thus, stereoisomers of the 10′-apo-11′,12′-dihydroauroxanthiiv 10′-ols 8. Valenciaxanthin represents a modification of the common cleavage of carotenoids in higher plants according to the scheme C40 → C27 + C13, insofar as the reduction step not only includes the aldehyde function but also the subsequent conjugated double bond.

Notizen: Dipolar 1:1 Adducts from the Reaction of 3-Amino-2H-azirines with 1,3,4-Oxadiazol- and 1,3,4-Thiadiazol-2(3H)-ones3-Amino-2H-azirines 1 react with 5-(trifluoromethyl)-1,3,4-oxadiazol-2(3H)-one (2) as well as with different 5-substituted 1,3,4-thiadiazol-2(3H)-ones (5a-e) in 2-propanol at room temperature to give dipolar 1:1 adducts of type 3 and 6, respectively, in reasonable-to-good yields (Schemes 3 and 6, Tab. 1 and 2). The structure of two of these dipolar adducts, 6a and 6e, which are formally donor-acceptor-stabilized azomethin imines, have been elucidated by X-ray crystallography (Figs. 1-4). In the reaction of 2 and sterically crowded 3-amino-2H-azirines 1c-e with a 2-propyl and 2-propenyl substituent, respectively, at C(2), a 4,5-dihydro-1,2,4-triazin-3(2H)-one of type 4 is formed as minor product (Scheme 3 and Table 1). Independent syntheses of these products proved the structure of 4. Several reaction mechanisms for the formation of compounds 3 and 4 are discussed, the most likely ones are described in Scheme 4: reaction of 2 as an NH-acidic compound leads, via a bicyclic zwitterion of type A, to 3 as well as to 4. In the latter reaction, a ring-expanded intermediate B is most probable.

Notizen: A theoretical study of the enantioselective Michael-type addition of chiral secondary enamines to enones has been achieved. In a first step, the structures of various free enamines have been investigated at the ab initio and MNDO levels. The results clearly show that upon substitution of the prototype vinylamine, the N-center is pyramidalized. The study of enamines with chiral N-substituents such as (S)-Ph(Me)CH or (S)-cyclohexyl(Me)CH reveals a very complex pattern, where up to 8 local energy minimums are characterized whose examination shows that no prediction can be. done regarding the final enantioselectivity of their reaction with enones. These sets of conformers can be regarded as nearly energetically degenerate, at least for the three or four ones of lowest energy. The study of the compact complexes formed between the latter optimal conformers and acrylaldehyde shows that: (i)syn complexation with respect to the N lone pair is the only one which remains possible for steric reason, (ii) small geometrical rearrangements take place as the complexation proceeds, (iii) no clear-cut correspondence exists between the relative sequence of the low-energy conformers of the free enamines and the sequence of the low-energy complexes, (iv) the examination of the relative gradients of the complexation energies provides an index for predicting the relative facilities of the enantiometric pathways, in good agreement with the experimental facts. Our study emphasizes the great complexity of systems of realistic size and brings about critical conclusions regarding classical ad hoc models.

Notizen: In three steps, 2-deoxy-D-ribose has been converted into a phosphoramidite building block bearing a (t-Bu)Me2Si protecting group at the OH function of the anomeric centre of the furanose ring. This building block was subsequently incorporated into DNA oligomers of various base sequences using the standard phosphoramidite protocol for automated DNA synthesis. The resulting silyl-oligomers have been purified by HPLC and selectively desilylated to the corresponding free apurinic DNA sequences. The hexamer d (A-A-A-A-X-A) (X representing the apurinic site) which was prepared in this way was characterized by 1H- and 31P-NMR spectroscopy. The other sequences as well as their fragments, which formed upon treatment with alkali base, were analyzed by polyacrylamide gel electrophoresis.

Notizen: An X-ray diffraction analysts of two N-acyl derivatives of symmetrical dialkylureas, N-[Nα-(benzyloxycarbonyl)-L-valyl] -N, N′-diisopropylurea (1) and N-{Nα(tert-butyloxy)carbonyl -L-valyl}-N-N′-dicyclohexylurea (2), and one N-acyl derivative of an unsymmetrical N-N′-dialkylurea, N-[Nα-(benzyloxycarbonyl)-L-valyl] -N′-(tert-butyl)-N-ethylurea (3), has been performed. It was established that it is the least hindered O-acylisourca N-atom that attacks intramolecularly the carbonyl group of the Nα-protected amino acid activated by the unsymmetrical carbodiimide to form the major rearrangement product. The occurrence and nature of intra- and intermolecularly H—bonded forms of the N-acylureas in the crystal state were also assessed. It was also shown that soluble N-acylureas may compete with intermolecular (peptide)N—H…O=C(peptide) H-bonds in CH2Cl2.

Notizen: The 1,4-addition of vinylmagnesium bromide/CuBr-SMe2 to (+)-(4s)-cryptone ((+)-6) in THF in the presence of Me3SiCI gives the silylenol ether 7 which partly undergoes hydrolysis to ketone 8 on aqueous workup; residual 7 is hydrolyzed with pyridinium p-toluenesulfonate (PyTsOH) to give 8 which is protected in situ with ethylene glycol and then ozonolized to give aldehyde (—)-10. The latter, on addition of 3-lithiofuran followed by dehydration and deprotection with Py TsOH, gives the unnatural (4S)-enantiomer (+)-2 of noroxopenlanfuran. All processes, except 11 → (+)-2, are of good yield. On the basis of previous chemical transformations, this also establishes the (4R)-configuration for penlanfuran ((-)-1) and other sesquiterpenoids of the sponge Dysidea fragilis from the North-Brittany sea. Non viable routes to (±)-noroxoperlanfuran ((±)-2) are also discussed.

Notizen: The use of [Pd(H2O)2(Ph2PCH2CH2PPh2)] (CF3SO3)2 as a catalyst for the acetalisation of a variety of aldehydes and ketones and for trans-acetalisation is described. It is also shown that Pt(H2O)2(PH2PCH2CH2PPh2) (CF3SO3)2 is at least as effective as the corresponding Pd compound, while much lower reaction rates are observed with [Rh(MeOH)2(Ph2PCH2CH2PPh2)] [BF4].

Notizen: Pd-Catalyzed Deuterium Exchange of Octa(silsesquioxane) H8Si8O12 to D8Si8O12Deuterium exchange on octa(silsesquioxane) H8Si8O12 to D8Si18O12 catalyzed by palladium on carbon is reported.

Notizen: Alkylation of 1,4,7-tritosyl-1,4,7,11-tetraazacyclotetradecane with CH2O/KCN or acrylonitrile gave the corresponding cyanomethyl or 2-cyanoethyl derivatives, which, by treatment with Na in BuOH, were detosylated and reduced to the macrocyclic pentaamines 1 and 2. The Ni2+ and Cu2+ complexes with 1 and 2 show a reversible pH-dependent change in geometry, in which the side-chain amino group is either coordinated to the metal ion (basic form) or protonated and, thus, non-coordinated (acidic form). The length of the side chain determines the log Ka values of these protonation/deprotonation equilibria: 1.89 and ∼ 2.0 for the Cu2+ and Ni2+ complexes of ligand 1 with the 2-aminoethyl side chain, and 6.17 and 7.43 for the Cu2+ and Ni2+ complexes of ligand 2 with the 3-aminopropyl side chain.

Notizen: Cyclic Phenyl Carbamates and Their Action on AcetylcholinesteraseSeveral six-, seven-, and eight-membered cyclic phenyl carbamates of the miotin type have been synthesised and their in vitro potency as inhibitors of acetylcholinesterase determined. The eight-membered rings were found to be the most potent and are comparable with physostigrnin or miotin. It was concluded that, for maximum potency, the orientation of the carbamate group relative to the aromatic plane has to be close to orthogonal.

Notizen: A New Synthetic Route to UbiquinonesUbiquinones 11 have been prepared employing a new strategy: as key step, the Diels-Alder reaction of 1,1,2-trichloroethene 3 with 2,5-bis[(trimethylsilyl)oxy]-3-methylfuran (2) has been used for the construction of the quinone part. After methanolysis of the [4 + 2] adducts 4a/4b, further reaction with cyclopentadiene and substitution of the Cl-atoms by MeO groups, the intermediate 7 is obtained. Diketone 7 can easily be alkylated with the desired polyprenyl side chain 9 (X = Br) using a strong base to yield, after a retro-Diels-Alder reaction, the corresponding ubiquinones 11 in high yields.

Notizen: Three new synthetic procedures for and thermal 1,6-electrocyclizations of acceptor-substituted 2,3-divinyl-1H-indoles leading to functionalizing carbazoles are described. The scope and limitations as well as some mechanistic aspects of the methodologies are discussed. The key strategies employed include Pd(II)-catalyzed coupling and Wittig procedures.

Notizen: Cis-3-(trans-1,2-Epoxybut-3-enyl)-4-vinylcyclopentene ((±)-4, caudoxirene) is a new gamete-releasing and gamete-attracting pheromone from the marine brown alga Perithalia caudata (Sporochnales). The key step of its synthesis is the diastereoselective alkylation of the aldehyde 8 with the [(phenylthio)allyl]titanium reagent 9 to yield the erythro-β-hydroxy sulfide 10 which affords 4 on sequential treatment with Me3O·BF4 and aq. NaOH. The lowest effective concentration of (±)-4 for gamete-release is found at 1.4 × 10-11 mol/l seawater.

Notizen: The isolation and structure elucidation of the new Spirostaphylotrichins N (2), O (3), P (4), and T (7) from a mutant strain of S. coccosporum are described. The biogenetic relationship of the known spirostaphylotrichins is discussed.

Notizen: Baker's yeast reduction of 4-methoxy-5,6,7,8-tetramethylidenebicyclo[2.2.2]octan-2-one (11) under fermenting conditions afforded (-)-(1S,2S,4R)-4-methoxy-5,6,7,8-tetramethylidenebicyclo[2.2.2]octan-2-ol ((-)-13) in 60% yield with an e.e. 〉 99.5%. Its methanesulfonate (-)-14 was hydrolyzed and rearranged with high stereo-selectivity into (+)-(1S,2S,5S)-5-methoxy-3,4,6,7-tetramethylidenebicyclo[3.2.1]octan-2-ol ((+)-15). The absolute configuration of (-)-13 was deduced from the CD spectrum of its 4-(dimethylamino)benzoate ((+)-22) applying the chiral exciton-coupling method. The CD spectrum of (+)-15 and of its (tert-butyl)dimethylsilyl ether ((+)-23) showed exciton-split type of Cotton effects attributed to through-space interactions between the s-gauche-buta-diene and s-cis-butadiene chromophores of these systems.

Notizen: Synthesis of (3S,4R,3′S,4′R)- and (3S,4S,3′S,4′S)-Crustaxanthins and Further Compounds with 3,4-Dihydroxy β-End-groupsStarting from 3, the enantiomerically pure title compounds were synthesized in eight steps. Spectra and HPLC systems are presented that allow a distinction between these isomers.

Notizen: A simple synthesis of 5-deoxy-L-[5-2H1]arabinose was performed to obtain L-[3′-2H1]biopterin. The reduced form of this model substance is needed to investigate the pathway of 7-substituted pterins in patients with primapterinuria.

Notizen: We describe a new principle for the purification of oligodeoxynucleotides using a purification handle which leads to a covalent linkage of the desired DNA sequence to a solid matrix. Truncated sequences are removed by washing steps. The release of the pure target sequence is performed in such a way that it is obtained directly in its 5′-phosphorylated form which represents a further advantage. In addition, the system can be used for 5′-thiol modifications of synthetic DNA.

Notizen: Total Synthesis of Naturally Occurring α-Tocopherol. Asymmetric Alkylation and Asymmetric Epoxidation as Means to Introduce (R)-Configuration at C(2) of the Chroman MoietyBased on the reductive, stereospecific ring closure of (2R,4′R,8′R)-α-Tocophcrylquinone′ or corresponding analogues with a short, functionalized side chain (B, Scheme 1) to 1 resp. the chroman system of 1 (C), two different approaches for the introduction of the required tertiary methyl-substituted alcohol structure in the side chain of the aromatic precursors (A, Scheme 1) were developed. The first approach uses asymmetric alkylation in three different versions featuring (a) diastereoselective steering with chiral auxiliaries I-IV (Scheme 2) attached as esters to a-keto acids, (b) intermediate transfer of chirality in an ester enolate (from 18, Scheme 4) derived from an optically active α-hydroxy acid, (c) enantioselective alkylation of phytenal (20) and subsequent ring closure with chirality transfer (Schemes 5-7). The second approach is based on the asymmetric epoxidation of β-metallylalcohol (Sharpless epoxidation), the corresponding epoxyalcohol being converted in situ to the (S)-or (R)-chlorodiol (S)-and (R)-29, respectively, for isolation (Schemes 8 and 9). Nucleophilic epoxide opening with a (3R 7R)-3,7,11-trimethyldodecyl (C15**) and an ArCH2 unit in appropriate sequence is used to assemble the C-framework of the target molecule via corresponding epoxide intermediates from either chlorodiol. Combined with the use of the methoxymethyl-ether function for protection of the hydroquinone system, the epoxide approach provides a short route to 1 (Scheme 10).

Notizen: The metastable ions of Fe+ complexes of aldimines R1N=CHR2 exhibit a unique behaviour in that sequential loss of olefin/H2 follows two distinct pathways: one corresponds to the familiar pattern of double remote functionalization, involving either alkyl chain R1 and R2. In addition, based on labeling studies, evidence is presented demonstrating that the consecutive elimination of C2H4/H2 from the Fe+ complex of C6H13N=CHC3H7 involves exclusively the C6H13 part of the substrate. These and other Fe+-mediated C—H/C—C bond activations of aldimines are controlled by chain-length effects, reflecting the preferential formation of metallacyclic intermediates of particular ring sizes.

Notizen: Compound (Z)-8a has been found to display interesting antiinflammatory activity. In order to prepare derivatives with a wide variety of substituents in the aromatic part of the molecule, a new synthesis of the key intermediates 9a-g was developed starting from thiophene-3-carboxylic acid (11) and substituted benzyl bromides. The conversion of 9a-g to 10a-g follows a known procedure. Ketones 10a-g, on reaction with alkyl (dialkoxy-phosphoryl)acetate, followed by isomer separation and alkaline ester hydrolysis, yielded the desired derivatives (Z)-8a-g and (E)-8a-g. The biologically most interesting compound (Z)-8a is currently undergoing clinical trials.

Notizen: The infrared quasi-resonance stepwise-multiphoton-dissociation spectra of the molecular ions of 1-bromo-propene, 2-bromopropene, 3-bromopropene, and bromocyclopropane have been obtained at selected wavelengths between 9. 2 and 10. 7 μm in a Fourier -transform mass spectrometer. The resulting spectra and the photo fragmentation kinetics suggest that these molecular ions retain their identity upon ionization, and can, thus, provide fingerprint spectral identifications for the ions.

Notizen: The absorption spectra, luminescence spectra, excited-state lifetimes, and electrochemical behavior of the cyclometalated [Rh(ppz)2bpy]+, [Rh(3-Cl-ppz)2(bpy)]+, [Rh(4-NO2-ppz)2(bpy)]+, [Rh(ppz)2(biq)]+ and [Rh(4-NO2-ppz)2(biq)]+ complexes (ppz-, 3-Cl-ppz-, and 4-NO2-ppz- are the ortho-C-deprotonated forms of 1-phenylpyrazole, l-(3-chlorophenyl)pyrazole and l-(4-nitrophenyl)pyrazole, respectively) have been investigated. The results obtained have been compared with those concerning the free protonated ligands and some previously studied mixed-ligand cyclometalated Rh(III) complexes. Luminescence originates from the lowest ligand-centered (LC) excited state, which involves the diimine ligands in all cases except for [Rh(4-NO2-ppz)2(bpy)]+, where it involves the ortho-metalating ligand. s. In the absorption spectra, LC and metal-to-ligand charge-transfer (MLCT) bands, involving the diimine and/or the ortho-metalating ligands, have been assigned, and correlations between spectroscopic and electrochemical data are discussed.

Notizen: The phosphonic acids 3 and 4 were prepared to compare their inhibitory activity on Vibrio cholerae sialidase with the one of the corresponding N-acetyl-2-deoxyneuraminic acids 5 and 6. Thus, hydrogenation and benzylation of methyl N-acetyl-2,3-didehydro-2-deoxyneuraminate (1MeNeu2en5Ac; 7) gave a mixture of the fully O-benzylated benzyl and methyl esters 9 and 10, the partially O-benzylated benzyl and methyl esters 11 and 12, and the fully O-and N-benzylated benzyl and methyl esters 13 and 14 (Scheme 1). Transesterification of 9 to 10 and hydrolysis of 10 gave the acid 15. Oxidative decarboxylation of 15 with Pb(OAc)4 gave a 1:9 mixture of the α-and β-D-glycero-D-galacto-acetates 16 and 17. Phosphonoylation of 17 with P(OMe)3 and Me3SiOTf gave a 1.3:1 mixture of the phosphonates 18 and 19, which were deprotected to give the (4-acetamido-2,4-dideoxy-D-glycero-α-and β-D-galacto-octopyranosyl)phosphonic acids 3 and 4, respectively. The acid 6 was obtained by epimerization of the tert-butyl ester 23 with lithium N-cyclohexylisoproylamide and deprotection. The phosphonic acids 3 (Ki 5.5 10-5 M) and 4 (Ki 2.3.10-4 M) are stronger inhibitors of Vibrio cholerae sialidase than the anomeric N-acetyl-2-deoxyneuraminic acids 5(Ki 2.3 10-3 M) and 6. Both 3 and 4 inhibit the Vibrio cholerae sialidase, while only the carboxylic acid 5, possessing an equatorial COOH group is an inhibitor.

Notizen: Zero-current counter-transport studies as well as electrodialytic transport experiments on solvent polymeric membranes doped with ionophores for anions have been carried out and were compared with potentiometric measurements on the same membranes. A theoretical description of the observed phenomena corroborates that lipophilic complexes of Co(III) (e. g. aquacyano[heptakis(2-phenylethyl)]Co(III) cobyrinate perchlorate) and Mn(III) (e. g. lipophilic Mn(III)porphyrin complexes) act as positively charged carriers for anions, whereas a lipophilic Ru(II)porphyrin complex has to be described as an electrically neutral carrier for anions.

Notizen: In four series of strictly related organocobalt complexes, derived from cobaloximes by replacement of the O…H…O with O…-BF2…O and/or (CH2)3 groups, the trends of 59Co-NMR shielding and electrochemical data are discussed. A largely parallel behaviour of the plots of E1/2(I) values for the first Co(III)/Co(II) electron transfer vs. the 59Co chemical shifts reflects the similar sensitivity of the two parameters to a change in electron affinity of the central metal ion due to a variation of the organic group R. E1/2(II) values for the second Co(II)/CO(I) electron transfer are less sensitive to the change of R, but the trend of the plot vs. δ(59Co) is still parallel in the four series. Consistent deviations from a roughly linear dependence of E1/2(I) on pKa of the hydrocarbon acid corresponding to R, on Taft constant s̰* and on 59Co shielding are noticed for the isopropyl derivatives and attributed to a steric effect. This was confirmed in a series of R—Co(DMG)pyridine complexes in which 59Co shielding decreases steadily with increasing steric parameter Es (Taft) of the alkyl group. There is experimental evidence from X-ray data that δ(59Co) decreases with an increase of the Co—C bond length, illustrating steric hindrance in alkyl coordination to be responsible for the decreased shielding of the 59Co nucleus. The relative displacements of the graphic displays for the different series reflect the effect of changes in electron affinity of the redox center, due to the equatorial ligand, which, in turn, is caused by variations in the electron-withdrawing power due to the introduction of the BF2 group and by the change from -2 to -1 valence of the (CH2)3-capped ligands.