bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of 4‐acetylcolchicine
Authors: Kouroupis Pavlos , Linden Anthony , Hansen Hans‐Jürgen
Published: December 2004

The synthesis of 4‐acetylcolchicine (1) by Swern dehydrogenation of the corresponding mixture of 4‐[(R)‐1‐hydroxyethyl]‐ and 4‐[(S)‐1‐hydroxyethyl]colchicine (3a and 3b, respectively) is described (cf. Scheme). The X‐ray analysis of 1 (cf. Fig.), crystallized from MeOH, showed the presence of MeOH in the crystals.
Synthesis of (15N2)[17O]Urea, (15N2)[O2, O4‐17O2]Uridine, and (15N3)[O2‐17O]Cytidine
Authors: Amantea Antonio , Henz Matthias , Strazewski Peter
Published: December 2004

A general synthetic approach for the synthesis of 15N‐ and 17O‐doubly labelled pyrimidine nucleosides is described. The 15N isotopes in uridine and the 17O isotope in the urea‐derived carbonyl group of uridine and cytidine originate from (15N2)[17O]urea (5) which was synthesized from 15NH4Cl, thiophosgene (1), and H2[17O]. The third 15N isotope of cytidine in 4‐position stems from the substitution of the 1,2,4‐triazole moiety of (15N2)[O2‐17O]uridine derivative 8a/b with 15NH4OH. Hydrolysis of the same key intermediate 8a/b with Na[17O]H/H2[17O] introduced the second 17O isotope into the 4‐position of uridine. The 15N‐ and 17O‐NMR spectra of the target compounds 12 and 14 in phosphate‐buffered H2O serve as references for heteronuclear NMR spectra of labelled RNA fragments.
Ring‐Opening Reaction of a Dihydrozirconafuran (= 2,5‐Dihydro‐1,2‐oxazirconole): An equilibrium studied by NMR methods, and its chemical consequences
Authors: Baumann Wolfgang , Ohff Andreas , Ebener Michael
Published: December 2004

The dihydrozirconafuran 3 (2,2‐di(cyclopenta‐2,4‐dien‐l‐yl)‐2,5‐dihydro‐5,5‐dimethyl‐3,4‐bis(trimethylsilyl)‐1,2‐oxazirconole) is a valuable synthetic equivalent to the 14‐electron fragment Cp2Zr

Throughout this paper, Cp=η5−C5H5

. The reactions of this metallacycle suppose an equilibrium with an ‘opened’ form [ZrCp2(RCCR)(acetone)], the latter paving the way to numerous ligand replacements. In a solution containing the dihydrozirconafuran and acetone, these reactions are reversible and degenerate, and can be studied by NMR methods: by two‐dimensional spectroscopy and by observation of the isotope‐induced chemical shifts that occur upon incorporation of (D6)acetone into the metallacycle. The findings give an indirect proof of the described equilibrium.
Ein alternativer Zugang zum PQQ‐Triester
Authors: Sicker Dieter , Stehfest Ekkehard , Wilde Horst , Martin Pierre
Published: December 2004

An Alternative Approach to the PQQ‐Triester

A novel approach to triethyl 5‐methoxy‐1H‐pyrrolo[2,3‐f]quinoline‐2,7,9‐tricarboxylate (6), a close precursor of the redox cofactor PQQ of bacterial dehydrogenases, is described. Diethyl 2‐oxopent‐3‐ynedioate (5) was used as building block for the annelation of the quinoline unit. The annelation proceeds in two steps via the diastereoselective formation of diethyl (Z)‐4‐{[2‐(ethoxycarbonyl)‐5‐methoxyindol‐6‐yl]amiono}‐2‐oxopent‐3‐enedioate ((Z)‐7) followed by acid‐catalyzed cyclocondensation.
ESR Study of Nitroxide Radicals Generated from Triaz‐2‐en‐1‐ols
Authors: Omelka Ladislav , Vrábel Imrich , Erentová Katarína , Dauth Jochen , Deubzer Bernward , Weis Johann
Published: December 2004

The triazenols 4‐R1C6H4NNN(OH)R2 (1), oxidized with t‐BuO radicals, produced nitroxide radicals R1C6H4N(O⋅)NN(R2) +O− (5). The suggested radical structure was confirmed by 15N‐labeling. The reaction of triazenols 1 with PbO2 proceeded under N2 elimination, in which case nitroxides R1C6H4N(R2)O⋅(2) were observed as the final radical products. The intermediate R1C6H radicals were identified by spin‐trapping.
Synthese monodisperser linearer und cyclischer Oligomere der (R)‐3‐Hydroxybuttersäure mit bis zu 128 Einheiten
Authors: Lengweiler Urs D. , Fritz Monica G. , Seebach Dieter
Published: December 2004

Monodisperse Linear and Cyclic Oligo[(R)‐3‐hydroxybutanoates] Containing up to 128 Monomeric Units

Using benzyl ester/(tert‐butyl)diphenylsilyl ether protection, (COCl)2/pyridine esterification conditions, and a fragment‐coupling strategy (with H2/Pd‐C debenzylation and HF · pyridine desilylation), linear oligomers of (R)‐3‐hydroxybutanoic acid (3‐HB) containing up to 128 3‐HB building blocks (mol. weight > 11 000 Da) are assembled (Schemes 1,2,5, and 6). In contrast to the previously employed protecting‐group combination, and due to the low‐temperature esterifying conditions, this procedure leads to monodisperse oligomers: all steps occur without loss of single 3‐HB units. The product oligomers with two, one, and no terminal protecting groups (mostly prepared in multi‐gram amounts) are characterized by all standard spectroscopic methods, especially by mass spectroscopy (Figs. 2 and 3), by their optical activity, and by elemental analyses. Cyclization of the oligo[(R)‐3‐hydroxybutanoic acids] with up to 32 3‐HB units, using thiopyridine activation and CuBr2 for the ring closure, produces oligolides consisting of up to 128 ring atoms (Scheme 7). Mixed oligolides containing 3‐HB and (R)‐3‐hydroxypentanoic units are prepared from the corresponding linear trimers, using Yamaguchi's method for the ring closure (Scheme 8 and Fig.4 (X‐ray crystal structures of two folded conformers)). Comparisons of melting points (Table 1), of [α] values (Tables 2 and 3), of 1H‐NMR coupling constants (Table 3), and of molecular volume/hydroxyalkanoate unit (Table 4) of linear and cyclic oligomer derivatives and of the high‐molecular‐weigh polymer show that the monodisperse oligomers appear to be surprisingly good models for the polymer. Besides this insight, our synthesis is supplying the samples to further test the role of P(3‐HB) (ca. 140 units) as a component of complexes forming channels through cell‐wall phospholipid bilayers.
Synthesen von 2,3‐Dioxoalkylphosphonaten und anderer neuartiger β‐Ketophosphonate sowie eines Phosphinopyruvamids ( = (Alkyloxyphosphinyl)pyruvamids)
Authors: Neidlein Richard , Feistauer Helmut
Published: December 2004

Syntheses of 2,3‐Dioxoalkylphonates and Other Novel β‐Ketophosphonates As Well As of a Phosphinopyruvamide ( = (Alkyloxyphosphinyl)pyruvamide)

The new 3‐(diethoxyphosphoryl)‐2‐oxopropanoates 5 and 6 and ‐propanamides 1–4 with various amino substituents at C(3) were prepared (Scheme 2). These compounds exist, depending on N‐substitution, as pure (E)‐enols (in the case of1 and 5) or as a mixture of three tautomeric forms (in the case of 1–4 and 6). The configuration could be unambiguously assigned from the 1H‐, 13C‐, and 31P‐NMR spectra. Phosphinopyruvamide ( = (alkyloxyphosphinyl)pyruvamide) 9 was prepared in a similar manner in spite of the instability of phosphinate derived carbanions. Some 3‐(ethoxyimino)‐2‐oxobutylphosphonates, 11–13 (Scheme 5), and various 3,3‐dimethoxy‐2‐oxoalkylphosphonates, 19–23 and 26–33 (Scheme 6), were available from the reaction of lithioalkylphosphonates with 2‐(ethoxyimino)propanoates and 2,2‐dimethoxyalkanoates, respectively. The 3,3‐dimethoxybutylphosphonates 20, and 26–30 were cleaved to give 2,3‐dioxobutylphosphonates 34–39 (Scheme 6). This method provides easy access to a new class of potentially pharmaceutically useful compounds.
Mimicking the Vancomycin Carboxylate Binding Site: Synthetic receptors for sulfonates, carboxylates, and N‐protected α‐amino acids in water
Authors: Hinzen Berthold , Seiler Paul , Diederich François
Published: December 2004

The novel H2O‐soluble cyclophanes 1 and 2 incorporating different anion‐recognition sites were prepared in short synthetic routes (Schemes 1 and 2) as first‐generation mimics of the natural, D‐Ala‐D‐Ala binding antibiotic vancomycin. The X‐ray crystal structure of 1, a tris(hydrochloride)salt, revealed an open, preorganized cavity of sufficient size for the incorporation of small aliphatic residues (Fig. 3). In the crystal, molecules of 1 are arranged in parallel stacks, generating two types of channels, an ‘intra‐stack’ channel passing through the cyclophane cavities and an ‘inter‐stack’ channel located between cyclophane stacks (Fig. 4). The strongest intermolecular interactions between macrocycles in the crystal are CO…︁HN H‐bonds between the carboxamide residues of adjacent cyclophanes in neighboring stacks (Fig. 5). The ‘intra‐’ and ‘inter‐stack’ channels incorporate the three ordered Cl− counterions and several, partially ordered solvent molecules (4 MeOH, 1 H2O) (Fig. 6). Counterion Cl(2) is located within the ‘intra‐stack’ channel and interacts with a protonated piperazinium N‐atom and both ‘intra‐stack’ MeOH molecules. The two other counterions, Cl(1) and Cl(3), are located within the ‘inter‐stack’ channel. They are connected to two MeOH and one H2O molecules and also interact both with the NH group of the protonated spiropiperidinium ring in 1, forming an infinite, chain‐like H‐bonding network …︁Cl(1)…︁HOH…︁MeOH…︁Cl(3)…︁HNH…︁Cl(1′)…︁. Both ‘intra‐’ and ‘inter‐stack’ MeOH molecules undergo weak CH…︁π interactions with neighboring aromatic rings. Cyclophane 1 complexed aromatic sulfonates in 0.5M KCl/DCl buffer in D2O, whereas the tetrakis(quaternary ammonium) receptor 2 bound the sodium salts of aliphatic and aromatic carboxylates and sulfonates, of N‐acylated α‐amino acids as well as of N‐acetyl‐D‐alanyl‐D‐alanine (Ac‐D‐Ala‐D‐Ala), a substrate of vancomycin, in pure H2O. In all of these complexes, ion pairing between the cationic recognition site in the periphery of the cyclophane receptor and the anionic substrates represents the major driving force for host‐guest association. The 1H‐NMR analysis of complexation‐induced changes in chemical shift clearly demonstrated that, in solution, this ion pairing exclusively takes place outside the cavity. Nevertheless, the macrocyclic bridges are essential for the efficiency of the anion‐recognition sites in the two cyclophane receptors 1 and 2. Control compounds 3 and 4 possess nearly the same anion‐recognition sites than 1 and 2, but lack their macrocyclic preorganization; as a consequence, they do not form stable ion‐pairing complexes with mono‐anionic substrates in the considered concentration ranges ( < 50 mM) in D2O.
Analogs of Cinchona Alkaloids Incorporating a 9,9′‐Spirobifluorene Moiety
Authors: Winter‐Werner Barbara , Diederich François , Gramlich Volker
Published: December 2004

The Cinchona alkaloid analogs (+)‐ and (−)‐5 with a quinuclidine‐2‐methanol residue attached to C(2) of a 9,9′‐spirobifluorene moiety were prepared as a racemic mixture by reacting lithiated 2‐bromo‐9,9′‐spirobifluorene 7 with (2‐ethoxycarbonyl)quinuclidine (±)‐6 to give ketone (±)‐8, followed by diastereoselective reduction with diisobutylaluminum hydride (DIBAL‐H). The absolute configuration at C(9) and C(8), i.e., at the methanol bridge and the adjacent quinuclidine C‐atom, in the two enantiomers of 5 is identical to the configuration at the corresponding centers in (−)‐quinine (1) and (+)‐quinidine (2), respectively. For the optical resolution of (±)‐5, a chiral stationary phase for HPLC was prepared by covalently bonding quinine via a thiol spacer to a silica‐gel surface. The enantiomer separation was accomplished at an α value of 1.61 with (±)‐5 being eluted last, in agreement with 1H‐NMR studies in CDCl3 which showed that (+)‐5 underwent a more stable host‐guest association with quinine than (−)‐5. 1H{1H} Nuclear Overhauser effect (NOE) difference spectroscopical analysis of the host‐guest associations with quinine in CDCl3, combined with computer‐model examinations, allowed the assignment of the absolute configurations as (+)‐(8R,9S)‐5 and (−)‐(8S,9R)‐5. A detailed conformational analysis displayed excellent agreement between the results of computational methods (Monte Carlo multiple minimum simulations, analyses of the total energy as a function of the flexible dihedral angles in the molecule) and 1H{1H}‐NOE difference spectroscopical data. It was found that (−)‐5 and (+)‐5 differ significantly in their conformational preference from their natural counterparts quinine (1) and quinidine (2). Whereas the natural alkaloids prefer the ‘open’ conformation, with the quinuclidine N‐atom pointing away from the quinoline ring, analog (±)‐5 adopts preferentially (by ca. 4 kcal mol−1) a ‘closed’ conformation, in which the quinuclidine N‐atom points into the cleft of the 9,9′‐spirobifluorene moiety. Since the basic quinuclidine N‐atom in the ‘closed’ conformation is sterically shielded from forming strong H‐bonds, the new Cinchona alkaloid analogs form less stable host‐guest associations via H‐bonding than quinine or quinidine.
The Diels‐Alder Reactivity of 2,2′‐Ethylidenebis[3,5‐dimethylfuran] and Exploratory Chemistry of the Mono‐adducts
Authors: Ancerewicz Jacek , Vogel Pierre , Schenk Kurt
Published: December 2004

In the presence of Me3Al, 1‐cyanovinyl acetate added to 2,2′‐ethylidenebis[3,5‐dimethylfuran] (1) to give a 20:10:1:1 mixture of mono‐adducts 4,5,6, and 7 resulting from the same regiocontrol (‘para’ orienting effect of the 5‐methyl substituent in 1). The additions of a second equiv. of dienophile to 4–7 were very slow reactions. The major mono‐adducts 4 (solid) and 5 (liquid) have 2‐exo‐carbonitrile groups. The molecular structure of 4(1RS,1′RS,2SR,4SR)‐2‐exo‐cyano‐4‐[1‐(3,5‐dimethylfuran‐2‐yl)ethyl‐7‐oxabicyclo[2.2.1]hept‐5‐en‐2‐endo‐yl acetate) was determined by X‐ray single‐crystal radiocrystallography. Mono‐adducts 4 and 5 were saponified into the corresponding 7‐oxanorbornenones 8 and 9 which were converted with high stereoselectivity into (1RS,1′SR,4RS,5RS,6RS)‐4‐[1‐(3,5‐dimethyl furan‐2‐yl)ethyl]‐6‐exo‐methoxy‐1,5‐endo‐dimethyl‐7‐oxabicyclo [2.2.1]heptan‐2‐one dimethyl acetal (12) and its (1′RS‐stereoisomer 12a, respectively. Acetal hydrolysis of 12a followed by treatment with (t‐Bu)Me2SiOSO2CF3 led to silylation and pinacol rearrangement with the formation of (1RS,1′RS,5RS,6RS)‐4‐[(tert‐butyl)dimethy lsilyloxy]‐1‐(3,5‐dimethylfuran‐2‐yl)ethyl]‐5‐methoxy‐6‐methyl‐3‐methylidene‐ 2‐oxabicyclo[2.2.1]heptane (16). In the presence of Me3Al, dimethyl acetylenedicarboxylate added to 12 giving a major adduct 19 which was hydroborated and oxidized into (1RS,1′RS,2″RS,3″RS,4SR,4″RS,5 SR,6SR)‐dimethyl 5‐exo‐hydroxy‐4,6‐endo‐dimethyl‐1‐[1‐(3‐exo,5,5‐trimeth oxy‐2‐endo,4‐dimethyl‐7‐oxabicyclo[2.2.1]hept‐2‐yl)ethyl]‐7‐oxabicyclo [2.2.1]hept‐2‐ene‐2,3‐dicarboxylate (20). Acetylation of alcohol 20 followed by CC bond cleavage afforded (1′RS,1″SR,2RS,2′″SR,3RS, 3″SR,4RS,4″SR,5RS)‐dimethyl {3‐acetoxy‐2,3,4,5‐tetrahydro‐2,4‐dimethyl‐5‐[1‐(3‐exo,5,5‐trimethoxy −2‐endo,4‐dimethyl‐7‐oxabicyclo[2.2.1]hept‐1‐yl)‐ethyl]furan‐2,5‐diyl} bis[glyoxylate] (24).
Biosynthesis of Dodecano‐4‐lactone in Ripening Fruits: Crucial Role of an Epoxide‐Hydrolase in Enantioselective Generation of Aroma Components of the Nectarine (Prunus persica var. nucipersica) and the Strawberry (Fragaria ananassa)
Authors: Schöttler Michael , Boland Wilhelm
Published: December 2004

Early steps in the biosynthesis of dedecano‐4‐lactone in ripening nectarines (Prunus persica var. nucipersica) and strawberries (Fragaria ananassa) were studied using cis‐9,10‐([18O]epoxy)heptadecanoic acid (5), instead of the natural C18‐precursor epoxystearic acid 1. In nectarines, an epoxide hydrolase catalyzed, in a highly regio‐ and enantioselective reaction, the attack of H2O at C(9) of epoxy acid 5 yielding preferentially (9R,10R)‐dihydroxyheptadecanoic acid 6a as an early intermediate and, after further metabolization, undecano‐4‐lactone 7a. In strawberries, the same transformation exhibited only a moderate regio‐ and enantioselectivity. Besides the previously established function of phytogenic epoxide hydrolases involved in generating oxygenated fatty‐acid derivatives, which are used in cutin monomer production and plant defence, a new rǒle for these enzymes now emerges in the enantioselective production of aroma components of ripening fruits. The cis‐9,10‐([18O]epoxy)heptadecanoic acid (≥ 98% 18O; 5) was obtained in good overall yield (68%) from isopropyl (9Z)‐heptadec‐9‐enoate using 18O2 gas in a free‐radical chain reaction in the presence of 2‐methylbutanal.
Stereoselektive Synthese des Nitrit‐reduzierenden Cofaktors Häm d1 ausgehend von Hämatoporphyrin
Authors: Romanowski Frank , Mai Gerhard , Kusch Dirk , Montforts Franz‐Peter , Bats Jan W.
Published: December 2004

Steroselective Synthesis of the Nitrite‐Reducing Cofactor Heme d1 from Hematoporphyrin

The nitrite‐reducing cofactor heme d1 has been synthesized in a few synthetic steps, starting from readily accessible hematoporphrin dimethyl ester (rac‐4a). A single‐crystal structure analysis of the synthesized target molecule rac‐10a unequivocally established the constitution and the relative configuration of heme d1 (3).
Säurekatalysierte Umlagerung von 9‐Hydroxyfuranoeremophilanen zu Eremophilanlactonen
Authors: Siegenthaler Peter , Neuenschwander Markus
Published: December 2004

Acid‐Catalyzed Rearrangement of 9‐Hydroxyfuranoeremophilanes to Eremophilanlactones

9‐Hydroxyfuranoeremophilanes 1–3 are the main components of freshly harvested rhizomes of P. hybridus (furanopetasin chemovar, Table, Fig. 1). They easily and quantitatively rearrange in the presence of traces of acid to give an epimeric mixture of 8‐H‐eremophilanlactones 4–6 (eremophilenolides, Table, Figs. 4 and 5). Besides subsequent oxidation (see 4 → 7), this is the most important reaction occuring during drying and storage of rhizomes of P. hybridus (Figs. 1 and 3). A reasonable mechanism of the rearrangement is presented, and spectroscopic structure elucidation of 8‐H‐eremophilanlactones is discussed.
Asymmetric Synthesis of 3‐Hydroxyprolines by Photocyclization of C(1′)‐Substituted N‐(2‐Benzoylethyl)glycine Esters
Authors: Steiner Andrê , Wessig Pablo , Polborn Kurt
Published: December 2004

The chiral N‐(2‐benzoylethyl)‐N‐tosylglycine esters 5a–h and the α‐amino‐γ‐keto ester 6 were prepared from γ‐(tosylamino) alcohols 7a–h. Irradiation of compounds 5a–c, e gave cis‐3‐hydroxyproline esters 20–23 (Scheme 6), partly with complete asymmetric induction by the C(1′)‐substituent, whereas 6 gave enantiomerically pure 4‐hydroxy‐4‐phenyl‐L‐proline esters 24 in good yield but low de (Scheme 6). The de of the photocyclization depended on the nature and/or size of the C(1′)‐substituents. Irradiation of ketones 5d and 5f, bearing H‐atoms at C(γ) with respect to the keto function, gave cyclobutanols (Scheme 9) in low yields besides the preferred Norrish‐type‐II cleavage product. Cyclopentanol 25 was a by‐product of the photocyclization of 5c as a result of HC(δ) abstraction from the t‐Bu group. The structure of products 20, 22, and 24a, b was established by NMR or X‐ray analyses.
Synthesis and Odor of Chiral Partial Structures of Khusimone. Part 1
Authors: Sprdizer Helmut , Pichler Andrea , Holzer Wolfgang , Toth Irene , Zuchart Bettina
Published: December 2004

Khusimone (1), one of the main odor‐donating compounds of vetiver oil is subject of the following study on structure/odor relationship. The omittance of the ethano bridge of the tricyclic khusimone leads to a bicyclic system. The stereoselective approach to this degraded structure is described, and the olfactory properties are studied. The key step of the synthesis of the hydrindane nucleus is based on a highly diastereoselective conjugate addition to a chiral oxo‐cyclopentene‐2‐carboxylate.
Ringöffnungen von sterisch gehinderten spirocyclischen 2, 5‐Dihydro‐1, 3, 4‐thiadiazolen mit cycloaliphatischen, sekundären Aminen
Authors: Miostoń Grzegorz , Romańsld Jaroslaw , Linden Anthony , Heimgartner Heinz
Published: December 2004

Ring Opening of Sterically Crowded Spirocyclic 2, 5‐Dihydro‐l, 3, 4‐thiadiazoles by Cycloaliphatic Secondary Amines

At room temperature, the spirocyclic 2, 5‐dihydro‐l, 3, 4‐thiadiazole 3 reacted with cyclic secondary amines 6 via ring opening to give N‐alkylidene‐hydrazones of type 7 (Scheme 2). A reaction mechanism via a base‐catalyzed transformation of the dihydrothiadiazole ring to the corresponding thiolate 19 and the intermediate thioaldehyde 21 is proposed in Scheme 6. An analogous reaction occurred with the mixture of the dispiro compounds 4/5 and morpholine (6a) or azetidine (6d), leading to a mixture of isomeric dihydrazones 8 and 9 (Scheme 3). The structure of the symmetrical isomer 8a was established by X‐ray crystallography. In addition to 8a and 9a, the thiirane lOa (Scheme 3) was isolated as a minor product.
3′‐(β‐D‐Glycopyranosyloxy)flavylium Ions: Synthesis and investigation of their properties in aqueous solution. Hydrogen bonding as a mean of colour variation
Authors: Hajji Hakima El , Dangles Olivier , Figueiredo Paulo , Brouillard Raymond
Published: December 2004

This work describes a straightforward synthesis of two 3′‐(β‐D‐glycopyranosyloxy)flavylium ions thought to be good models of natural anthocyanins (pigments). For both pigments and for the non‐glycosylated flavylium ion taken as a reference, H2O addition and proton‐transfer reactions as well as formation of molecular complexes with chlorogenic acid and caffeine (copigmentation) are quantitatively investigated in mildly acidic aqueous solution. A remarkable affinity of caffeine for the trans‐chalcone form of the pigments is demonstrated. Moreover, the differences in the flavylium pKa values are interpreted in terms of possible intramolecular H‐bonding between the glycosyl residue and the chromophore. The discussion is then extended to a series of malonylated anthocyanins recently reported for their unusual pigmentation properties. A possible role for the malonyl group (frequently encountered in the structure of naturally occurring anthocyanins) in plant colour expression is outlined for the first time.
Wechselwirkungen in Kristallen. 106. Mitteilung. Die Klaviatur der Na⊕‐Koordinationszahlen in ihren Carbazolanion‐Salzen
Authors: Bock Hans , Arad Claudia , Nather Christian , Havlas Zdenek
Published: December 2004

Interaction in Crystals: The Keyboard of Na⊕ Coordination Numbers in Its Carbazole Anion Salts

Some local minima in the shallow potential of the system carbazole anion, sodium cation, and the ethers tetrahydrofuran, 1,2‐dimethoxyethane, diglyme, triglyme, tetraglyme, 15‐crown‐5 as well as 2.2.1‐cryptand are explored experimentally and by quantum‐chemical calculations. Three prototype contact‐ion multiples of Na⊕‐solvated carbazole anion M⊖ salts have been crystallized and structurally characterized: polyether‐solvated monomers [M⊖Na⊕solv]1, solvent‐shared dimers [M⊖Na⊕solv]2, and solvent‐separated polyions [(M⊖)nNa⊖solv](n−1)− [Na⊕solv](n−1). The Na⊕ coordination numbers stretch from 3 to 7 as illustrated by the compounds [(M−)3Na+]⊖⊖[Na+(2.2.1‐crytand)]2 for 3 and 7, [(M−)2Na+(THF)2]⊖ [Na⊕(2.2.1‐cryptand)] for 4 and 7, [M− Na+(diglyme)]2 for 5, or [M− Na+(l 5‐crown‐5)] for 6. Structural comparison is based on literature analogies as well as on results of MNDO calculations concerning charge distribution and enthalpies of formation. Taken together, the results demonstrate the delicate energy balance, by which cation solvation can influence the formation of organic salts.
Synthesis of Modified Tripeptides and Tetrapeptides as potential bisubstrate inhibitors of the epidermal growth factor receptor protein tyrosine kinase
Authors: Rossé Gérard , Séquin Urs , Mett Helmut , Furet Pascal , Traxler Peter , Fretz Heinz
Published: December 2004

The synthesis of a series of bisubstrate inhibitors of the epidermal growth factor receptor protein kinase (EGF‐R PTK) consisting of small pep tides linked covalently to adenosine via appropriate triphosphate substitutes is described. Boc‐Glu(OtBu)‐Tyr‐Leu‐OBzl (5) and Ac‐Glu(OtBu)‐Tyr‐Leu‐Arg(Pmc)‐NH2 (8; Pmc = 2,2,5,7,8‐pentamethylchroman‐6‐sulfonyl) were prepared by standard peptide chemistry, (Scheme 1), then modified at the OH group of tyrosine either with adipic anhydride or with 4‐(chlorosulfonyl)benzoic acid, 4‐(chlorosulfonyl)‐2‐hydroxybenzoic acid, or benzene‐1,4‐disulfonyldichloride (Scheme 2), and finally coupled with the 5′‐OH group of 2′,3′‐O‐isopropylideneadenosine (Scheme 3). In addition, N6‐[(benzyloxy)carbonyl]‐2′,3′‐O‐isopropylidene‐adenosine 5′‐(hydrogenhexanedioate) (26), an ATP substitute, was coupled with the morpholide of 5 (Scheme 4). Removal of the protecting groups gave the bisubstrate analogs 23, 24, and 28. The compounds synthesized were tested as inhibitors of the EGF‐R PTK. The most active bisubstrate‐type inhibitor was 24, composed of the tripeptide sequence H‐Glu‐Tyr‐Leu‐OBzl, the 2‐hydroxy‐4‐sulfonylbenzoyl moiety, and adenosine; it showed an IC50 value of 33 μM.
Synthèse de (3‐aminopropyl)arylsilanes, comportant un ou deux motifs hétérocycliques, fongicides potentials
Authors: Garandeau Par Jean‐Marc , Chollet Jean‐FrançOis , Miginiac Léone
Published: December 2004

Synthesis of (3‐Aminopropyl)arylsilanes, Including One or Two Heterocyclic Patterns, Potential Fungicides

Flusilazole is an effective silylated fungicide used on a large scale for plant protection. We synthesized several flusilazole analogs and also copied the tebuconazole design, an other very efficient fungicide, which has four atoms between the aromatic group and the heterocyclic moiety. In contrast to flusilazole, we obtained dissymetric structures around the Si‐atom by using successively two different Grignard reagents. In another way, the 1H‐1,2,4‐triazole moiety was exchanged in several cases by other N‐heterocycles such as 1H‐imidazole, piperidine, and 2,6‐dimethylmorpholine, already present in other fungicidal compounds. Finally, several compounds having two N‐heterocycles of the same or different nature were prepared.
Synthesis of Cyclic Depsipeptides and Peptides via Direct Amide Cyclization
Authors: Villalgordo José M. , Heimgartner Heinz
Published: December 2004

The 2,2‐disubstituted 2H‐azirin‐3‐amines 7 (2,2‐disubstituted 3‐amino‐2H‐azirines) were used as amino‐acid synthons in the preparation of medium‐sized cyclic depsipeptides and peptides derived from salicylic acids 6 and anthranilic acid 19, respectively (Schemes 2‐‐4 and 5, resp.). The combination of the ‘azirine/oxazolone method’ for the synthesis of linear peptides containing α,α‐disubstituted α‐amino acids and the acid‐catalyzed amide cyclization in DMF at 60° proved to be an excellent preparative route to ten‐membered cyclic depsipeptides and peptides. In the case of the anthranilic‐acid derivative, a transannular ring‐closure reaction was observed (24 → 25). Larger rings proved to be extremely sensitive to hydrolysis.
Quantitative Analysis of Enzyme‐Mediated Hydrolytic Processes and Their Products Using HPLC and NMR Techniques
Authors: Wimmer Zdenêk , Zarevúcka Marie , Rejzek Martin , Šaman David , Zhao Qiu‐Yu , Legoy Marie‐Dominique
Published: December 2004

Second derivatives of the UV spectra of 2‐(4‐alkoxybenzyl)cyclopentan‐1‐ols and their acetates were used for the quantitative analysis of reaction kinetics of enzyme‐mediated hydrolytic process. To determine the enantiomeric purity of the products using non‐chiral HPLC columns, their diastereoisomeric esters of 3,3,3‐trifluoro‐2‐methoxy‐2‐phenylpropanoic acid(MTPA) were prepared. The absolute configuration of the products was established using a combination of the results of a HPLC analysis and 1H/19F‐NMR measurements of the diastereoisomeric MTP esters. The analytical method described consists of an easy routine HPLC analysis which can sometimes be used as a quick on‐line analysis of the reaction kinetics and as a quick stepwise analysis of the optical purity and the absolute configuration of the products.
Diazoaldehyde Chemistry. Part 4vilsmeier‐haack formylation of diazo compounds: A re‐investigation
Authors: Sezer Özhan , Dabak Kadir , Anaç Olcay , Akar Ahmet
Published: December 2004

Diazomethyl ketones (2‐diazoethanones) were reacted with the Vilsmeier reagent ((chloromethylidene)dimethylammonium chloride) to yield α‐diazo‐β‐oxoaldehydes and chloromethyl ketones. 2′,4′‐Dimethoxy‐α‐diazoacetophenone gave 2‐chloro‐1‐(2,4‐dimethoxyphenyl)‐3‐(dimethylamino)prop‐2‐en‐1‐one (5) in addition to the expected products. Phenyldiazomethanes gave the corresponding benzyl chlorides but not the (phenyl)diazoacetaldehydes even at temperatures as low as −60°. The diazo‐transfer reactions of phenylacetaldehydes and 2‐azido‐1‐ethylpyridin‐1‐ium tetrafluoroborate also did not yield the expected(phenyl)diazoacetaldehydes.
Chiral 2‐Aryl‐2‐methyl‐2H‐1‐benzopyrans: Synthesis, characterization of enantiomers, and barriers to thermal racemization
Authors: Harié Guenäelle , Samat André , Guglielmetti Robert , van Parys Inge , Saeyens Wim , de Keukeleire Denis , Lorenz Klaus , Mannschreck Albrecht
Published: December 2004

The ease of thermal breaking of the C(sp3)O bond of the 2‐aryl‐2‐methyl‐2H‐1‐benzopyrans 1–9 was evaluated by measuring the free energy (ΔG) of the racemization reaction of optically active compounds. The variation of ΔG of the thermal ring opening in terms of structural modifications is discussed. The synthesis of the studied compounds, the preparative separation of enantiomers by liquid chromatography, the determination of enantiomeric purity, the circular dichroism of enriched enantiomers, and the measurement of rate constants of enantiomerization by monitoring the decrease of the polarimetric angle of rotation at suitable temperatures are described.
Synthesis and Evaluation of 2‐{[(2‐Oxo‐1H‐quinolin‐8‐yl)oxy]methyl}‐Substituted α‐Methylidene‐γ‐butyrolactones
Authors: Tzeng Cherng‐Chyi , Chen Yeh‐Long , Wang Chyi‐Jia , Wang Tai‐Chi , Chang Ya‐Ling , Teng Che‐Ming
Published: December 2004

O‐Alkylation of 8‐hydroxy‐1H‐quinolin‐2‐one (1) afforded 8‐(2‐oxopropoxy)‐1H‐quinolin‐2‐one (2) which was immediately cyclized to form the tricyclic 2,3‐dihydro‐3‐hydroxy‐3‐methyl‐5H‐pyrido[1,2,3‐de][1,4]benzoxazine,‐5‐one (3). The Reformatsky‐type condensation of 3 furnished antiplatelet 8‐[(2,3,4,5‐tetrahydro‐2‐methyl‐4‐methylidene‐5‐oxofuran‐2‐yl)melhoxy]‐1H‐quinolin‐2‐one (4). Its counterparts 7a–f, Ph‐substituted at C(2) of the furan ring, were obtained from 1 via alkylation and the Reformatsky‐type condensation. Although compound 4 was less active against platelet aggregation than 7a–f, it was the only compound which exhibited significant inhibitory activity on high‐K+ medium, Ca2+‐induced vasoconstriction and was more active than most of its Ph‐substituted counterparts against norepinephrine‐induced vasoconstrictions.
Reformulating the Kinetic Approach of Column Chromatography for a Single Component
Authors: Kuznetsov Alexander M. , Giraultb Hubert H.
Published: December 2004

The kinetic model of column chromatography is revisited to explicitly show that this approach yields, when neglecting axial dispersion, a rather simple analytical expression depending only on two dimensionless parameters, namely a dimensionless kinetic retention parameter and a dimensionless time parameter. An expression for the time corresponding to the maximum of the peak is also proposed.
Design and Synthesis of Potent Macrocyclic Benzolactam Growth Hormone Secretagogues
Authors: De Vita Robert J. , Frontier Alison J. , Schoen William R. , Wyvratt Matthew J. , Fisher Michael H. , Cheng Kang , Chan Wanda W.‐S. , Butler Bridget S. , Smith Roy G.
Published: December 2004

The synthesis of a variety of potent macrocyclic growth hormone secretagogues, i.e. 5, 9, 12, and 20–22, based on the known lead structure L‐692,429 (1) is described. These conformationally constrained growth hormone secretagogues were prepared by joining the two essential pharmacophores, the amino‐acid side chain at the 1H‐1‐benzazepine moiety and the 1,1′‐biphenyl moiety with a variety of linkers. The most potent analog was found to be L‐744,080 (21), a derivative in which a 2′‐carboxamide moiety at 1,1‐biphenyl is N,O‐joined to the OH group of the (2‐hydroxypropyl)amino‐acid side chain by a C4 ester linker. This potent analog may be useful in determining the bound conformation of the benzolactam class of growth hormone secretagogues at the newly identified GHS receptor, L‐744,080 (21) with an ED50 of 20 nM was up to fifty times more potent than the seco‐acid precursor and 3‐fold more potent than the parent 2′‐tetrazole compound L‐692, 429 (1).
Cyclic Heptapeptides Axinastatin 2, 3, and 4: Conformational analysis and evaluation of the biological potential
Authors: Mechnich Oliver , Messier Gerhard , Kessler Horst , Bernd Michael , Kutscher Bernhard
Published: December 2004

The conformational analysis of naturally occurring cytostatic cyclic heptapeptides axinastatin 2, 3, and 4 was carried out by two‐dimensional NMR spectroscopy in combination with distance‐geometry (DG) and molecular‐dynamics (MD) calculations in explicit solvents. The synthesized secondary metabolites were examined in (D6)DMSO. Axinastatin 2 was also investigated in CD3OH. In all structures, Pro2 is in the i + 1 position of a βI turn and Pro6 occupies the i + 2 position of a βVIa turn about the cis amide bond between residue 5 and Pro6. In all peptides, a bifurcated H‐bond occurs between residue 4 CO and the amide protons of residue 1 and 7. For axinastatin 2 and 3, an Asn Ig turn was found about Asn1 and Pro2. We compared these structures with conformations of cyclic heptapeptides obtained by X‐ray and NMR studies. A β‐bulge motif with two β turns and one bifurcated H‐bond is found as the dominating backbone conformation of cyclic all‐L‐heptapeptides. Axinastatin 2, 3, and 4 can be characterized by six trans and one cis amide bond resulting in a β/βVI(a)‐turn motif, a conformation found for many cyclic heptapeptides. Detailed biological tests of the synthetic compounds in different human cancer cell lines indicates these axinastatins to be inactive or of low activity.
Novel Heterospirocyclic 3‐Amino‐2H‐azirines as Synthons for Heterocyclic α‐Amino Acids
Authors: Strässler Christoph , Linden Anthony , Heimgartner Heinz
Published: December 2004

The heterospirocyclic N‐methyl‐N‐phenyl‐2H‐azirin‐3‐amines (3‐(N‐methyl‐N‐phenylamino)‐2H‐azirines) 1a‐d with a tetrahydro‐2H‐thiopyran, tetrahydro‐2H‐thiopyran, and a N‐protected piperidine ring, respectively, were synthesized from the corresponding heterocyclic 4‐carboxamides 2 by consecutive treatment with lithium diisopropylamide (LDA), diphenyl phosphorochloridate (DPPCI), and sodium azide (Scheme 4). The reaction of these aminoazirines with thiobenzoic acid in CH2Cl2 at room temperature gave the thiocarbamoyl‐substituted benzamides 13a‐d in high yield. The azirines 1a‐d were used as synthons for heterocyclic α‐amino acids in the preparation of tripeptides of the type Z‐Aib‐Xaa‐Aib‐N(Ph)Me (18) by following the protocol of the ‘azirine/oxazolone method’: treatment of Z‐Aib with 1 to give the dipeptide amide 15, followed by selective hydrolysis to the corresponding acid 16 and coupling with the 2,2‐dimethyl‐2H‐azirin‐3‐amine 17 gave 18, again in high yield (Scheme 5). With some selected examples of 18, the selective deprotection of the amino and the carboxy group, respectively, was demonstrated (Scheme 6). The solid‐state conformations of the protected tripeptides 18a‐d, as well as that of the corresponding carbocyclic analogue 18e, were determined by X‐ray crystallography (Figs. 1‐3 and Tables 1‐3). All five tripeptides adopt a β‐turn conformation of type III or III′. The solvent dependence of the chemical shifts of the NH resonances (Fig. 6) suggests that there is an intramolecular H‐bond between H‐N(4) and O(11) in all cases, which is an indication that a relatively rigid β‐turn structure also persists in solution. Surprisingly, the tripeptide acid 20a shows no intramolecular H‐bond in the crystalline state (Fig. 7); O(11) is involved in an intermolecular H‐bond with the OH group of the carboxy function.
Syntheses and Chiroptical Properties of the 13‐membered spermidine alkaloids (−)‐(S)‐celacinnine, (0)‐(S)‐celabenzine, (−)‐(S)‐celafurine, and (+)‐(S)‐viburnine
Authors: Kuehne Paul , Guggisberg Armin , Hesse Manfred
Published: December 2004

The title alkaloids were prepared from the common chiral precursor (−)‐(2S)‐2‐phenyl‐1, 5, 9‐triazacy‐clotridecan‐4‐one (4) which we had synthesized earlier. The spectral data for the spermidine macrocycles are in good agreement with the data reported for the isolated samples. Our experimental results indicate that the originally reported [α]D value of −2.6 (c = 0.10, MeOH) for natural (S)‐viburnine is erroneous and should be + 17.0 (c = 0.92, MeOH). As a result of the chiroptical study conducted, it can be shown empirically that all alkaloids of the ‘celacinnine’ type have the (S)‐configuration.
Nucleotides. Part LIV. Synthesis of condensed N1‐(2′‐deoxy‐β‐D‐ribofuranosyl)lumazines, New fluorescent building blocks in oligonucleotide synthesis
Authors: Rosler Angelika , Pfleiderer Wolfgang
Published: December 2004

Various condensed areno[g]lumazine derivatives 2, 3, and 5–7 were synthesized as new fluorescent aglycones for glycosylation reactions with 2‐deoxy‐3, 5‐di‐O‐(p‐toluoyl)‐α/β‐D‐erythro‐pentofuranosyl chloride (10) to form, in a Hilbert‐Johnson‐Birkofer reaction, the corresponding N1‐(2′‐deoxyribonucleosides) 15–21. The β‐D‐anomers 15, 17, 19, and 21 were deblocked to 24–27 and, together with N1‐(2′‐deoxy‐β‐D‐ribofuranosyl)lumazine (22) and its 6, 7‐diphenyl derivative 23, dimethoxytritylated in 5′‐position to 28–33. These intermediates were then converted into the 3′‐(2‐cyanoethyI diisopropylphosphoramidites) 34–39 which function as monomeric building block in oligonucleotide syntheses as well as into the 3′‐(hydrogen succinates) 40–45 which can be used for coupling with the solid‐support material. A series of lumazine‐modified oligonucleotides were synthesized and the influence of the new nucleobases on the stability of duplex formation studied by measuring the Tm values in comparison to model sequences. A substantial increase in the Tm is observed on introduction of areno[g]lumazine moieties in the oligonucleotide chain stabilizing obviously the helical structures by improved stacking effects. Stabilization is strongly dependent on the site of the modified nucleobase in the chain.
Glycosylidene Carbenes. Part 24 Reactivity modulation by protecting groups of the addition of glycosylidene carbenes to electron‐rich alkenes
Authors: Waldraff Christian , Bernet Bruno , Vasella Andrea
Published: December 2004

The reactivity of glycosylidene carbenes derived from pivaloylated vs. benzylated diazirines 1 and 2 towards enol ethers have been examined. The pivaloylated 1 led to higher yields of spirocyclopropanes than the benzylated 2. Among the enol ethers tested, dihydrofuran 6 proved most reactive, yielding 71–72% of the spiro‐linked tetrahydrofuran 7, while the benzylated diazirine 2 afforded only 33% of the analogue 8 (Scheme 1 ). Other enol ethers proved much less reactive. The addition of 1 and 2 to the dihydropyran 10 and the 2, 3‐dihydro‐5‐methyl‐furan 15 gave low yields of single cyclopropanes (→ 12, 14, and16), and the glycals 17 and 18, and (E)‐1‐methoxy‐oct‐1‐ene (23) did not react. The main products of these reactions were the azines (Z, Z)‐ 11 and (Z, Z)/( E, E)‐13. Similarly, 1 and 2 reacted poorly with (Z)‐1‐methoxyoct‐1‐ene (24), leading to cyclopropanes 25/26/27 and 28/29/30/31 (Scheme 2). Main products were again the azines (Z, Z)‐11 and (Z, Z)/(E, E)‐13. The structure of 70 and 25 was established by X‐ray analysis (Figs. 1 and 2). The mechanism of addition of glycosylidene carbenes to enol ethers is discussed, AMI Calculations indicate that the LUMOcarbene/HOMOalkoxyalkene interaction is dominant at the beginning of the reaction, while the transition states are characterized by a dominant interaction of the doubly occupied, sp2‐hybridized orbital of the carbene with the LUMO of the enol ether. The relative reactivity of the carbenes towards either the enol ethers or the diazirines determine type and yields of the products.
Control of regio‐, diastereo‐, and enantioselectivity in the [Ti(OTs)2(TADDOLato)]‐catalyzed 1,3‐dipolar cycloaddition reaction between 3‐acryloyloxazolidin‐2‐one and nitrones
Authors: Jensen Kim B. , Gothelf Kurt V. , Jørgensen Karl Anker
Published: December 2004

Catalytic control of regio‐, diastereo‐, and enantioselectivity in the 1,3‐dipolar cycloaddition of 3‐acryl‐oyloxazolidin‐2‐one (4) with different nitrones 2 by the application of a [TiX2(TADDOLato)] complex as the catalyst was developed (TADDOL = α,α,α′,α′‐tetraaryl‐1,3‐dioxolane‐4,5‐dimethanol). In the absence of a catalyst, the 1,3‐dipolar cycloaddition of 4 with 2 proceeded to give a mixture of regioisomers, whereas, in the presence of a catalyst, the regioselectivity of the reaction could be controlled. Three asymmetric [TiX2(TADDOLato)] catalysts were tested, and it was found that use of the [Ti(OTs)2(TADDOLato)] complex gave complete regioselectivity, high ‘endo’‐selectivities (> 90% d.e.), and enantioselectivities corresponding to 48–70% e.e.
Preparation of ortho‐aryl‐benzaldehyde derivatives via free‐radical ipso‐substitution of an amidomethyl group
Authors: Giraud Luc , Lacǒte Emmanuel , Renaud Philippe
Published: December 2004

Preparation of 2‐biarylcarbaldehydes using an intramolecular free‐radical ispo‐substitution is described. The two aryl moieties to be coupled are pre‐associated using a glycolamide derivative. An unusual amidomethyl leaving group was successfully employed in this process.
Oligosaccharide analogues of polysaccharides. Part 14:. Carbocyclic cyclodextrin analogues. Synthesis of all trimeric and tetrameric isomers by homo‐ and heterocoupling of 1,4‐cis‐diethynylated 1,5‐anhydroglucitols
Authors: Bürli Roland , Vasella Andrea
Published: December 2004

Hetero‐ or homocoupling of protected 1,4‐cis‐diethynylated 1,5‐anhydroglucitols leads to two isomeric cyclotrimers and to four isomeric cyclotetramers. The C3‐symmetric cyciotrimer 31, the C4‐symmetric cyclotetramer 35, and the D2‐symmetric cyclotetramer 6 have been prepared before. We have now synthesized the C1‐symmetric cyciotrimer 13, and the C1‐ and the C2‐symmetric cyclotetramers 22 and 27, respectively. The cyclotrimer 13 was prepared by intramolecular, oxidative homocoupling and, alternatively, by a one‐pot trimerization/cyclization of the monomer 36 (Schemes 1 and 5, resp.). Oxidative homocoupling was used for the cyclization of the tetramers 19 and 25, leading to 22 and 27. The tetramer 19 was made by sequential Cadiot‐Chod‐kiewicz coupling (Scheme 2)and the tetramer 25 by a combination of a Cadiot‐Chodkiewicz reaction and an intermolecular, oxidalive homocoupling (Scheme 3). The acetates 34 and 38, corresponding to 35 and 27, respectively, were also made by a one‐pot dimerization/cyclization of the dimer 37 (Scheme 5). Intramolecular oxidative heterocoupling is also feasible and results in an alternative, more convenient synthesis of the acetylated cyclotrimer 30 and the acetylated cyclotetramer 34 (corresponding to 31 and 35, resp.; Scheme 4). The solid‐state conformation of the C4‐symmetric cyclotetramer 34 corresponds well to the one predicted by force‐field calculations. We compared the water‐solubilities of the cyclotrimers 13 and 31 and the tetramers 6, 22, 27, and 35, their calculated conformations (MM3*), and the D‐adenosine binding properties of the cyclotetramers 6, 27, and 35.
An Efficient Synthesis of Enantiomeric Ribonucleic Acids from D‐Glucose
Authors: Pitsch Stefan
Published: December 2004

Enantiomeric oligoribonucleotides (= ent‐RNA) up to a sequence length of thirty‐five and consisting of the (L‐configurated) nucleosides ent‐adenosine, ent‐guanosine, ent‐cytidine, ent‐uridine, and 1‐(β‐L‐ribofuranosyl)thymine were prepared by automated synthesis from appropriate building blocks, carrying a known photo‐labile 2′‐O‐protecting group. A simple large‐scale synthesis of the new, prefunctionalized L‐ribose derivative 5 from D‐glucose (Scheme 1) and its straightforward conversion into the five phosphoramidites 28–32 and five solid supports 38–42, respectively, were elaborated (Scheme 4). Within this project, a novel, superior strategy for the synthesis of the 2′‐O‐{[(2‐nitrobenzyl)oxy]methyl}‐substituted key intermediates 18–22 by regioselective alkylation of their 5′‐O‐dimethoxytritylated precursors 13–17 was developed. Furthermore, an improved set‐up for the final light‐induced cleavage of the 2′‐O‐protecting groups from the oligonucleotide sequences was designed (Scheme 5 and Fig. 1). The correct composition of all ent‐oligoribonucleotides prepared was established by their MALDI‐TOF mass spectra. The 1H‐NMR‐spectroscopic data of a dodecameric ent‐RNA sequence was in excellent agreement with the published data of its natural counterpart, synthesized by conventional methods. The known specific cleavage of a tetradecamer sequence by a 35mer ribozyme structure could be reproduced by ent‐oligoribonucleotides, synthesized by the presented methods (Fig. 4).
Metal Complexes with Macrocyclic Ligands. Part XLVI. Synthesis and structures of dinuclear metal complexes of bis‐macrocycles having a pyrazole bridging unit
Authors: Weller Harald , Siegfried Liselotte , Neuburger Markus , Zehnder Margareta , Kaden Thomas A.
Published: December 2004

Three bis‐macrocyclic ligands consisting of two N3‐, N2S‐, or NS2‐cyclononane rings, i.e., of two octahydro‐1H‐1,4,7‐triazonine, octahydro‐1,4,7‐thiadiazonine, or hexahydro‐5H‐1,4‐7‐dithiazonine rings, connected by a 1H‐pyrazolediyl unit were prepared. They form dinuclear CuII and NiII complexes which are able to bind one additional exogenous bridging molecule such as Cl−, Br−, N, SO, and 1H‐pyrazol‐1‐ide. The structures determined by X‐ray diffraction show that each Cu2+ is coordinated by the three donor atoms of the macrocyclic ring, by a pyrazolidodiyl N‐atom, by an atom of the exogenous bridging ligand, and sometimes by a solvent molecule. In the majority of the Cu2+ cases, the metal ion exhibits square‐pyramidal or trigonal‐bipyramidal coordination geometry, except in the sulfato‐bridged complex, in which one Cu2+ is hexacoordinated with the participation of a water molecule. The X‐ray structure of the azide‐bridged dinuclear Ni2+ complex was also solved and shows that both Ni2+ centres have octahedral coordination geometries. In all complexes, the 1H‐pyrazolediyl group connecting the macrocycles is deprotonated and bridges the two metal centres, which, depending on the exogenous ligand, have distances between 3.6 and 4.5 Å. In the dinuclear Cu2+ complexes, antiferromagnetic coupling is present. The azido‐bridged complex shows a very strong interaction with −2J ≥ 1040 cm−1; in contrast, the H‐pyrazol‐1‐ide and chloride bridged species have −2J values of 300 and 272cm−1, respectively. Cyclic voltammetry of the Cu2+ complexes in MeCN reveals a strong dependence of the potentials CuII/Cu‐II → CuII/CuI → CuI/CuI on the nature of the donor atoms of the macrocycle as well as on the type of bridging molecule. The more S‐donors are present in the macrocycle, the higher is the potential, indicating a stabilization of the Cu1 oxidation state.