bluuebunny/crossref_metadata_2025 huggingface dataset:
Reactivity of 5,10:8,14‐Disecosteroids: An unusual rearrangement of cyclodecene‐1,4‐dione systems to five‐membered‐ring spiro‐γ‐lactones
Authors: Lorenc Ljubinka , Bondarenko‐Gheorghiu Lidija , Krstić Natalija , Fuhrer Hermann , Kalvoda Jaroslav , Mihailović Mihailo Lj.
Published: December 2004

Upon heating in AcOH, the stereoisomeric (Z)‐ and (R)‐6,9‐dioxocyclodex‐3‐enyl derivatives, 5 and 6, respectively, obtained by HgO/I2 oxidation of 5‐hydroxy‐8‐oxo‐8,14‐seco‐5α‐androstane‐3β,17β‐diyl diacetate (3), undergo an unusual intramolecular rearrangement to give the corresponding unsaturated (5R,9R)‐ and (5R,9S)‐spiro‐lactones 7 and 8, respectively. Hydroxylation of the CC bond in 7 and 8, and subsequent glycol cleavage of the resulting diols 9 and 10 afforded the epimeric spiro‐lactones (5R,9S)‐11 and (5R,9R)‐14, respectively, and in both cases, the ring‐D‐containing fragments 12 and 13.
Carbenoid Reactions in Rhodium(II)‐Catalyzed Decomposition of Iodonium Ylides
Authors: Müller Paul , Fernandez Daniel
Published: December 2004

The intermediacy of metallocarbenes in decomposition reactions of iodonium ylides with [Rh2(OAc)4] was established by comparison with reactions of the corresponding diazo compounds. The sensitivity of the RhII‐catalyzed intermolecular cyclopropane formation from substituted styrenes and bis(methoxycarbonyl)(phenyliodono)methanide (1a) or dimethyl diazomalonate (1b) is identical. The Hammett plot (with σ+) has a slope of −0.47. Iodonium ylides and diazo compounds afford the same products in [Rh2(OAc)4]‐catalyzed cyclopropane formations, cycloadditions, and intramolecular CH insertions, and exhibit the identical selectivity in intramolecular competitions for cyclopropane formation and insertion. The intramolecular CH insertion of the ylide 20c, when carried out in the presence of a chiral catalyst ([Rh2{(−)‐(S)‐ptpa}4]), results in formation of 21a having an ee of 67%, identical to the ee obtained with the diazo compound 20b.
Efficient Control of the Stereoselectivity in Reactions of 2‐Oxy‐Substituted Benzylic Radicals
Authors: Moufid Nadira , Renaud Philippe , Hassler Carla , Giese Bernd
Published: December 2004

The stereoselectivity in reactions of 2‐oxy‐substituted radicals of type B was investigated. As expected, minimization of allylic 1,3‐strain was the major controlling factor. Under standard conditions, only a modest level of stereoselectivity was observed. E.g., deuteration of the benzylated radical (R1 = benzyl) gave diastereoisomer ratios ≤ 2:1. Use of a bulky protective group on the O‐atom (R1 = (t‐Bu)Ph2Si) enhanced slightly the selectivity (ratio 4.1:1). However, a dramatic increase of the stereoselectivity (ratio 13:1) was obtained, when the reaction was performed with the free alcohol after treatment with bulky methylaluminium bis(phenoxide) derivatives (methyl‐aluminium bis[2,6‐di(tert‐butyl)‐4‐methylphenoxide] (MAD) and methylaluminium bis(2,6‐diphenylphenoxide) (MAPH)).
exo/endo‐Selectivity in the Reaction of ‘Bare’ FeO+ with Bicyclo[2.2.1]heptane (Norbornane)
Authors: Schwarz Joseph , Schwarz Helmut
Published: December 2004

‘Bare’ FeO+ reacts in the gas phase with norbornane with collision efficiency, and the most prominent cationic products correspond to [FeC5H6]+ (32%), [FeC7H8]+ (19%), [FeC3H6O]+ (19%) and [FeC6H6]+ (14%), which are structurally characterized by ligand exchange as well as collision‐induced dissociation experiments. Circumstantial evidence is provided which indicates that the complexes [FeC5H6]+, [FeC7H8]+, and [FeC6H6]+ originate from an Fe(norbornene)+ intermediate which itself is formed by elimination of H2O from the [FeO(norbornane)]+ encounter complex. Although the reactions are preceded and/or accompanied by partial H/D exchange, the isotope distribution in the productions clearly points to a preferential endo‐attack of bare FeO+, with an endo/exo‐ratio of ca. 10.3 and kinetic isotope effects kH/kD for the endo‐abstraction of 2.4 and of 7.7 for approaching an exo‐CH bond. The preferred endo‐approach of bicyclo[2.2.1]heptane by ‘bare’ FeO+ is in distinct contrast to the P‐450‐mediated or the iron(III)porphyrin‐catalyzed hydroxylation of this substrate which favor reactions at the exo‐face.
Erstes Beispiel einer H‐Verschiebung in ‘Thiocarbonyl‐aminiden’ (N‐(Alkylidensulfonio)aminiden)
Authors: Mlostoń Grzegorz , Romański Jaroslaw , Linden Anthony , Heimgartner Heinz
Published: December 2004

First Example of an H‐Shift in ‘Thiocarbonyl Aminides’ (N‐(Alkylidenesulfonio)aminides)

Reaction of benzyl azide (15a) with the sterically hindered CS group of 4,4‐dimethyl‐1,3‐thiazole‐5(4H)‐thiones 14 (Scheme 3) and 1,1,3,3‐tetramethylindane‐2‐thione (17, Scheme 4) at 80° leads to the corresponding imines in high yield, without formation of any by‐product. In contrast, 15a and 2,2,4,4‐tetramethyl‐3‐thioxocyclobutanone (7) under the same conditions yielded, in addition to imine 19, products 20a and 21 (Scheme 5). For the formation of 20a, a reaction mechanism via [1,4]‐H shift in the intermediate ‘thiocarbonyl aminides’ 23 is proposed (Scheme 6). Product 21 as well as the dithiazole derivative 22, which is formed only in the reaction with 4‐nitrobenzyl azide (15c), are formal adducts of the dipole 23. Whereas precedents are known for the formation of cycloadducts of type 22, the pathway to 21 is not known. Two possible mechanisms of its formation are proposed in Schemes 8 and 9.
Solid‐State Photocyclodimerization of 1‐Thiocoumarin (= 2H‐1‐Benzothiopyran‐2‐one)
Authors: Klaus Christian P. , Thiemann Carolin , Kopf Jürgen , Margaretha Paul
Published: December 2004

Irradiation (λ > 390 nm) of 2H‐1‐benzothiopyran‐2‐one (1) in the solid state affords selectively 6aα,6bα,12bα,12cα ‐tetrahydrocyclobuta[1,2‐c:4,3‐c′]bis[1]benzothiopyran ‐6,7‐dione (2), the head‐to‐head (HH) cis‐cisoid‐cis‐dimer, while irradiation of 1 in the solid state using shorter wavelengths (λ > 340 nm) affords a mixture of all four cis‐fused tricyclic dimers 2–5. These results represent a novel wavelength effect in solid‐state photochemistry.
Synthesis and First Applications of a New Chiral Auxiliary (tert‐butyl 2‐(tert‐butyl)‐5,5‐dimethyl‐4‐oxoimidazolidine‐1‐carboxylate)
Authors: Studer Armido , Hintermann Tobias , Seebach Dieter
Published: December 2004

Both enantiomers of tert‐butyl 2‐(tert‐butyl)‐5,5‐dimethyl‐4‐oxoimidazolidine‐1‐carboxylate (11; Bbdmoic) were prepared from L‐alanine (Schemes 1 and 2). The parent heterocycle, 2‐tert‐butyl‐5,5‐dimethylimidazolidin‐4‐one (12; from 2‐aminoisobutyramide, H‐Aib‐NH2, and pivalaldehyde) was also available in both enantiomeric forms by resolution with O,O′‐dibenzoyltartaric acid. The compound (R)‐ or (S)‐11 was used as an auxiliary, but also as a chiral Aib building block in a dipeptide synthesis. The 3‐propanoyl derivative 13 of (R)‐11 was used for the preparation of enantiomerically pure 2‐methyl‐3‐phenylpropanoic acid (enantiomer ratio (e.r.) 99.5:0.5), by benzylation of the Zn‐enolate (→ 14; Scheme 3). Oxidative coupling of the bis‐enolate derived from heptanedioic acid and (S)‐11 (→ 23) and methanolysis of the auxiliary gave dimethyl trans‐cyclopentane‐1,2‐dicarboxylate (26) with an e.r. of 93:7 (Scheme 5, Fig. 5). The 3‐(Boc‐Gly)‐Bbdmoic derivative 29 was doubly deprotonated and, after addition of ZnBr2 alkylated with alkyl, benzyl, or allyl halides to give the higher amino‐acid derivatives with excellent selectivities (e.r. > 99.5:0.5, Schemes 6 and 7). Michael additions of cuprates to [(E)‐MeCHCHCO]‐Bbdmoic 36 occurred in high yields, but high diastereoselectivities were only observed with aryl cuprates (diastereoisomer ratio (d.r.) 99:1 for R = Ph, Scheme 8). Finally, 3‐(Boc‐CH2)‐Bbdmoic 17 was alkylated through the ester Li‐enolate with primary and secondary alkyl, allyl, and benzyl halides with diastereoselectivities (ds) ranging from 91 to 98%, giving acetals of Boc‐Aib‐Xxx‐O(t‐Bu) dipeptides (Scheme 4). The effectiveness of Bbdmoic is compared with that of other chiral auxiliaries previously used for the same types of transformations.
Formation of Heptaleno[1,2‐c]furans and Heptaleno[1,2‐c]furanones
Authors: Uebelhart Peter , Mohler Peter , Fallahpour Reza‐Ali , Hansen Hans‐Jürgen
Published: December 2004

The dehydrogenation reaction of the heptalene‐4,5‐dimethanols 4a and 4d, which do not undergo the double‐bond‐shift (DBS) process at ambient temperature, with basic MnO2 in CH2Cl2 at room temperature, leads to the formation of the corresponding heptaleno[1,2‐c]furans 6a and 6d, respectively, as well as to the corresponding heptaleno[1,2‐c]furan‐3‐ones 7a and 7d, respectively (cf. Scheme 2 and 8). The formation of both product types necessarily involves a DBS process (cf. Scheme 7). The dehydrogenation reaction of the DBS isomer of 4a, i.e., 5a, with MnO2 in CH2Cl2 at room temperature results, in addition to 6a and 7a, in the formation of the heptaleno[1,2‐c]‐furan‐1‐one 8a and, in small amounts, of the heptalene‐4,5‐dicarbaldehyde 9a (cf. Scheme 3). The benzo[a]heptalene‐6,7‐dimethanol 4c with a fixed position of the CC bonds of the heptalene skeleton, on dehydrogenation with MnO2 in CH2Cl2, gives only the corresponding furanone 11b (Scheme 4). By [2H2]‐labelling of the methanol function at C(7), it could be shown that the furanone formation takes place at the stage of the corresponding lactol [3‐2H2]‐15b (cf. Scheme 6). Heptalene‐1,2‐dimethanols 4c and 4e, which are, at room temperature, in thermal equilibrium with their corresponding DBS forms 5c and 5e, respectively, are dehydrogenated by MnO2 in CH2Cl2 to give the corresponding heptaleno[1,2‐c]furans 6c and 6e as well as the heptaleno[1,2‐c]furan‐3‐ones 7c and 7e and, again, in small amounts, the heptaleno[1,2‐c]furan‐1‐ones 8c and 8e, respectively (cf. Scheme 8). Therefore, it seems that the heptalene‐1,2‐dimethanols are responsible for the formation of the furan‐1‐ones (cf. Scheme 7). The methylenation of the furan‐3‐ones 7a and 7e with Tebbe's reagent leads to the formation of the 3‐methyl‐substituted heptaleno[1,2‐c]furans 23a and 23e, respectively (cf. Scheme 9). The heptaleno[1,2‐c]furans 6a, 6d, and 23a can be resolved into their antipodes on a Chiralcel OD column. The (P)‐configuration is assigned to the heptaleno[1,2‐c]furans showing a negative Cotton effect at ca. 320 nm in the CD spectrum in hexane (cf. Figs. 3–5 as well as Table 7). The (P)‐configuration of (–)‐6a is correlated with the established (P)‐configuration of the dimethanol (–)‐5a via dehydrogenation with MnO2. The degree of twisting of the heptalene skeleton of 6 and 23 is determined by the Me‐substitution pattern (cf. Table 9). The larger the heptalene gauche torsion angles are, the more hypsochromically shifted is the heptalene absorption band above 300 nm (cf. Table 7 and 8, as well as Figs. 6–9).
On the Funicolides, Briaranes of the Pennatulacean Coral Funiculina quadrangularis from the Tuscan Archipelago: Conformational preferences in this class of diterpenes
Authors: Chiasera Giuseppe , Guerriero Antonio , D'Ambrosio Michele , Pietra Francesco
Published: December 2004

Kinetic and equilibrium NMR studies of briarane diterpenes isolated from the pennatulacean coral Funiculina quadrangularis showed that funicolide A (1), funicolide D (5), and brianthein W (6), with R2 = Hβ, undergo slow flipping by rotation of the C(1)C(2)C(3)C(4) dihedral angle, giving rise to two observable conformers in a 4:96 population ratio, both having an axial AcOC(14) and C(16) pointing ‘downwards’, but differing for pseudoaxial or pseudoequatorial position of R1O, respectively. δ(C) for the minor conformers could be quickly assigned by an original emulation methodology. Similar studies revealed that funicolide B (2), 7‐epifunicolide A (4), funicolide E (7), and unnatural epibrianthein W (8) undergo similar motions, where, however, the nature of the α‐positioned substituent R2 determines which conformer predominates: axial R1O for R2 = Hβ (4 and 8) or equatorial R1O for R2 α‐OH, (2 and 7). In contrast, funicolide C (3) proved to undergo slow conformational motions that involve also the cyclohexene ring, resulting in two observable conformers characterized by either an equatorial AcOC(14) and trans‐diaxial C(2)/C(9) or an axial AcOC(14) and trans‐diequatorial C(2)/C(9) in a 9:1 population ratio, respectively. These observations, and molecular‐mechanics calculations for briaranes known to exhibit broad NMR signals, lead to general views on the conformational preferences of diterpenes of this class.
4‐Amino‐1,5‐dihydro‐2H‐pyrrol‐2‐one aus Bortrifluorid‐katalysierten Umsetzungen von 3‐Amino‐2H‐azirinen mit Carbonsäure‐Derivaten
Authors: Hugener Martin , Heimgartner Heinz
Published: December 2004

4‐Amino‐1,5‐dihydro‐2H‐pyrrol‐2‐ones from Boron Trifluoride Catalyzed Reactions of 3‐Amino‐2H‐azirines with Carboxylic Acid Derivatives

Reaction of 3‐amino‐2H‐azirines 1 with ethyl 2‐nitroacetate (6a) in refluxing MeCN affords 4‐amino‐1,5‐dihydro‐2H‐pyrrol‐2‐ones 7 and 3,6‐diamino‐2,5‐dihydropyrazines 8, the dimerization product of 1 (Scheme 2). Thus, 6a reacts with 1 as a CH‐acidic compound by CC bond formation via C‐nucleophilic attack of deprotonated 6a onto the amidinium‐C‐atom of protonated 1 (Scheme 5). The scope of this reaction seems to be rather limited as 1 and 2‐substituted 2‐nitroacetates do not give any products besides the azirine dimer 8 (see Table 1). Sodium enolates of carboxylic esters and carboxamides 11 react with 1 under BF3 catalysis to give 4‐amino‐1,5‐dihydro‐2H‐pyrrol‐2‐ones 12 in 50–80% yield (Scheme 3, Table 2). In an analogous reaction, 3‐amino‐2H‐pyrrole 13 is formed from 1c and the Li‐enolate of acetophenone (Scheme 4). A reaction mechanism for the ring enlargement of 1 involving BF3 catalysis is proposed in Scheme 6.
Preparation, Structure, and Properties of All Possible Cyclic Dimers (Diolides) of 3‐Hydroxybutanoic Acid
Authors: Seebach Dieter , Hoffmann Torsten , Kühnle Florian N. M. , Kinkel Joachim N. , Schulte Michael
Published: December 2004

In connection with the proposed structure of a trans‐membrane cellular ion channel consisting of a complex between poly[(R)‐3‐hydroxy butanoate] (P(3‐HB)) and calcium polyphosphate, CaPPi (ca. 150 units each), which is supposed to contain s‐cis‐bonds or even more highly strained ester conformations, we have prepared and studied the properties of the cyclic dimer of 3‐HB, the diolide 1. All possible forms of 1, the rac‐, the meso‐, and the enantiomerically pure (R,R)‐ and (S,S)‐compounds were prepared, purified, and characterized. The synthesis (Scheme 1) started from dimethyl succinate with the key step being the Baeyer‐Villiger oxidation of the rac‐ and meso‐2,5‐dimethylcyclohexane‐1,4‐diones 5. The rac‐diolide 1 was resolved by preparative chromatography on a Chiralcel OD column (Fig.1). The crystal structures of rac‐ 1 (Fig.3) and of meso‐ 1 (Fig.5) were determined by X‐ray diffraction: the diolides 1 contain s‐cis‐ester bonds and an ester group with a conformation half way to the transition state of rotation (Fig.2). Strain energies for the diolides 1 of up to 17.8 kcal/mol are suggested. Accordingly, these compounds show reactivities similar to those of carboxylic‐acid anhydrides or even acid chlorides. They cannot be chromatographed on silica gel, and they react with primary, secondary, and tertiary alcohols, and with amines to form derivatives of open chain 3‐HB ‘dimers’, hydroxy acids 6, esters 7, and amides 8 (Scheme 2). The rate of acid‐catalyzed ring opening of the diolides 1 with alcohols has been measured (Fig.6 and 7). From the results described, we conclude that it is unlikely for strained and reactive ester conformations to occur as part of ion channels through phospholipid bilayers of cells.
Reaction of 5,6,7,8‐Tetrahydropterin with Iron(III) Acetylacetonate. Detection of Radical Cations by Electrospray Ionization Mass Spectrometry
Authors: Schäfer Andrea , Hesse Manfred , Viscontini Max , Paul Henning , Fischer Berthold
Published: December 2004

The experimental conditions developed for the detection of rather stable radical cations in solution by electrospray‐ionization mass spectrometry (ESI‐MS) of a FeII complex of 2‐amino‐5,6,7,8‐tetrahydro‐5‐methylpteridin‐4 (3H)‐one (1c) are used to observe the formation of the more unstable radical cations formed from 2‐amino‐5,6,7,8‐tetrahydropteridin‐4(3H)‐one (1a) and tris(pentane‐2,4‐dionato)iron(III) ([FeIII(acac)3]; 4) and to monitor their oxidation to the corresponding p‐quinonoid dihydropterin complexes. These results contribute to the understanding of the important role played by 6β‐5,6,7,8‐tetrahydro‐L‐biopterin (1b; a homologue of 1a) together with iron as constituent of some cofactors. The complexes obtained from 1a and iron may be considered, e.g. as a model of the cofactor of the phenylalanine hydroxylase. Moreover, we describe an improved synthesis of 1c.
Glycosylidene Carbenes. Part 22. α‐D‐Selectivity in the Glycosidation by Carbenes Derived from 2‐Acetamido‐hexoses
Authors: Vasella Andrea , Witzig Christian
Published: December 2004

Glycosylidene carbenes derived from the GlcNAc and AllNAc diazirines 1 and 3 were generated by the thermolysis or photolysis of the diazirines. The reaction of 1 with i‐PrOH gave exclusively the isopropyl α‐D‐glycoside of 5 besides some dihydrooxazole 9 (Scheme 2). A similar reaction with (CF3)2CHOH yielded predominantly the α‐D‐anomer of 6, while glycosidation of 4‐nitrophenol (→7) proceeded with markedly lower diastereoselectivity. Similarly, the Allo‐diazirine 3 gave the corresponding glycosides 12–14, but with a lower preference for the α‐D‐anomers (Scheme 3). The reactions of the carbene derived from 1 with Ph3COH (→8) and diisopropylideneglucose 10 (→11) gave selectively the α‐D‐anomers (Scheme 2). The αD‐selectivity increases with increasing basicity (decreasing acidity) of the alcohols. It is rationalized by an intermolecular H‐bond between the acetamido group and the glycosyl acceptor. This H‐bond increases the probability for the formation of a 1,2‐cis‐glycosidic C–O bond. The gluco‐intermediates are more prone to forming a N–H…︁(H)OR bond than the allo‐isomers, since the acetamido group in the N‐acetylallosamine derivatives forms an intramolecular H‐bond to the cis‐oriented benzyloxy group at C(3), as evidenced by δ/T and δ/c experiments.
The Directionality of d‐Orbitals and Molecular‐Mechanics Calculations of Octahedral Transition‐Metal Compounds
Authors: Comba Peter , Ströhle Marc , Hambley Trevor W.
Published: December 2004

A novel approach to modeling the angular geometry about the metal centre in transition‐metal complexes, using a variation of classical molecular‐mechanics calculations, is presented. The approach is based on the combination of 1,3‐nonbonded interactions around the metal centre and a harmonic sine function with a ligandfield‐dependent force constant for the L–M–L′ terms. Force‐field parameters for four‐, five‐, and six‐coordinated first‐row transition‐metal coordination centres and a variety of ligands containing N‐, S‐, and O‐donor sets are given. The new ‘electronically doped’ force field is shown to generally lead to computed structures with higher accuracy than those obtained when the coordination geometries are modeled with 1,3‐nonbonded interactions alone.
Cascade Cyclizations of Terpenoid Polyalkenes Triggered by Photoelectron Transfer – Biomimetics with Photons
Authors: Warzecha Klaus‐Dieter , Xing Xuechao , Demuth Martin , Goddard Richard , Kessler Magnus , Krüger Carl
Published: December 2004

Light‐induced cyclizations of suitably functionalized polyalkene terpenoids, such as geranyl, all‐trans‐farnesyl, and all‐trans‐geranylgeranyl derivatives, via formation of radical cations are proven to be a powerful method for the single‐step synthesis of mono‐ and mostly all‐trans‐fused polycyclic compounds from readily available precursors. Whereas some of these highly stereo‐ and chemoselective transformations required the use of micel ar media, they can now be conveniently performed in homogeneous solutions upon suitable choice of the electron acceptors and of the functionality pattern of the polyalkene substrates. Moreover, the mode of cyclization, i.e., 6‐ vs. 5‐membered ring formation and termination of the cyclization cascades, are steered efficiently by the substituents of the polyalkenes (polyalkenyl acetate vs. α,β‐unsaturated ethyl polyalkenoate and polyalkene‐1,1‐dicarbonitrile). At the same time, the protic solvents used add highly stereoselectively to the ω‐alkene sites of the polyalkens in anti‐Markovnikov sense which strongly suggests that radical cations are intercepted. Interestingly, the transformations achieved here upon photoelectron transfer parallel the biosynthetic paths of non‐oxidative terpene cyclizations which are thought to occur purely by protonation of the isoprenoid polyalkenes.
Fullerene‐Acetylene Molecular Scaffolding: Chemistry of 2‐functionalized 1‐ethynylated C60, oxidative homocoupling, hexakis‐adduct formation, and attempted synthesis of C
Authors: Timmerman Peter , Witschel Lars E. , Diederich François , Boudon Corinne , Gisselbrecht Jean‐Paul , Gross Maurice
Published: December 2004

On the way to the fullerene‐acetylene hybrid carbon allotropes 2 and 6, the oxidative homocoupling of the 2‐functionalized 1‐ethynylated C60 derivatives 11, 12, 14, and 15 was investigated. Under Glaser‐Hay conditions, the two soluble dumbbell‐shaped bisfullerenes 17 and 18, with two C60 moieties linked by a buta‐1,3‐diynediyl bridge, were formed in 52 and 82% yield, respectively (Scheme 2). Cyclic‐voltammetric measurements revealed that there is no significant electronic communication between the two fullerene spheres via the buta‐1,3‐diynediyl linker. Removal of the 3,4,5,6‐tetrahydro‐2H‐pyran‐2‐yl (Thp) protecting groups in 18 gave in 80% yield the highly insoluble dumbbell 19 with methanol groups in the 2,2′‐positions of the buta‐1,3‐diynediyl‐bridged carbon spheres. Attempted conversion of 19 to the all‐carbon dianion 6 (C) via base‐induced elimination of formaldehyde was not successful presumably due to exo‐dig cyclization of the formed alkoxides. The occurrence of this cyclization under furan formation was proven for 2‐[4‐(trimethylsilyl)buta‐1,3‐diyn‐1‐yl][60]fullerene‐1‐methanol (21), a soluble model compound for 19 (Scheme 3). To compare the properties of ethynylated fullerene mono‐adducts to those of corresponding higher adducts, hexakis‐adducts 26 and 28 with an octahedral functionalization pattern resulting from all‐e (equatorial) additions were prepared by the reversible‐template method of Hirsch (Scheme 4). Reaction of the ethynylated mono‐adducts 25 or 13 with diethyl 2‐bromomalonate/1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) in the presence of 1,9‐dimethylanthracene (DMA) as reversible template led to 26 and 28 in 28 and 22% yield, respectively. Preliminary experiments indicated a significant change in reactivity and NMR spectral properties of the fullerene addends with increasing degree of functionalization.
The Self‐Recognition and Self‐Assembly of Folic Acid Salts in Isotropic Water Solution
Authors: Gottarelli Giovanni , Mezzina Elisabetta , Spada Gian Piero , Carsughi Flavio , Nicola Giovanni Di , Mariani Paolo , Sabatucci Annalaura , Bonazzi Stefania
Published: December 2004

The self‐assembly of alkaline folates in isotropic water solutions, with or without added salts, has been investigated by small‐angle neutron‐scattering, circular‐dichroism, and NMR techniques. The assembled species are chiral, cylindrical aggregates of finite length, composed of stacked tetramers; each tetramer is formed by Hoogsteen‐bonded folate residues. The assembly process is more efficient in the presence of an excess of NaI ions, leading to longer aggregates with stronger tetramer‐tetramer‐tetramer interaction. In pure water, the rods are shorter and the tetramer‐tetramer interaction weaker. Association between folates can be detected by circular‐dichroism spectroscopy starting from a concentration of 6· 10−4 mol l−1, well below the critical concentration for the formation of the cholesteric mesophase (ca. 0.5 mol l−1).
Synthesis of a Building Block for a Nucleic‐Acid Analog with a Chiral, Flexible Peptide Backbone
Authors: Savithri Dhanalekshmi , Leumann Christian , Scheffold Rolf
Published: December 2004

We present here a nine‐step synthesis of the thymine‐containing amino ester 1, starting from commercially available methyl N‐[(tert‐butoxy)carbonyl]‐L‐serinate. Amino ester 1 is considered as a building block for the preparation of a new nucleic‐acid analog with a chiral, flexible polyamide backbone. Key steps in the synthesis are the vitamin‐B12‐catalyzed addition of 3‐bromo‐N‐[(tert‐butoxy)carbonyl]‐L‐alaninate 2 to ethyl acrylate and the homologation of the corresponding N‐protected α‐amino acid 4 into the β‐amino ester 6 by Arndt‐Eistert chemistry. The latter was found to proceed with 10% inversion of configuration at the asymmetric center in 6. Resolution to enantiomerically pure material, however, was easily achieved by simple crystallization of 1.
Chiral Acylsilanes in Organic Synthesis. Part 3. Silicon‐directed stereoselective preparation and Ireland ester‐enolate rearrangement of O‐acyl‐substituted α‐silylated allyl alcohols
Authors: Enev Valentin , Stojanova Diana , Bienz Stefan
Published: December 2004

Stereocontrolled addition of alk‐1‐enylmetal reagents to the chiral (alkoxymethyl)‐substituted acylsilanes (±)‐6 gave rise to α‐silylated allyl alcohols, which were converted to the corresponding acetates or propionates 11–16 (Scheme 2). Deprotonation and silylation with Me3SiCl afforded – in an Ireland ester‐enolate‐accelerated Claisen rearrangement – stereoselectively αδ‐silylated γδ‐unsaturated carboxylic acids 18–24 (Scheme 4). The Me3Si groups in α‐position to the COOH group of these compounds were removed chemoselectively in presence of the chiral silyl group in δ‐position by treatment with Bu4NF · 3 H2O or Et3N · 3 HF (→ 27–32; Scheme 5). The reaction sequence allows a novel stereocontrolled access to chiral C‐frameworks possessing a vinylsilane moiety with its full reaction potential.
The Tandem Pauson‐Khand Reaction
Authors: Thommen Marc , Veretenov Andrei L. , Guidetti‐Grept Régine , Keese Reinhart
Published: December 2004

The conditions for the novel tandem Pauson‐Khand reaction have been explored. The highly functionalized tetracyclic compounds 11c, 11d, and 16 were prepared from the ene‐diynes 4c, 4d, and 10 by treatment with 2 equiv. of [Co2(CO)8] and 4‐methylmorpholine N‐oxide (NMO) or Me3NO in yields of 24, 22, and 53%, respectively (Table). In the presence of 1–3 equiv. of H2O added to the NMO used for induction of the Pauson‐Khand reaction of 6d, a mixture of cyclopentanones 17/18 and cyclopentenones 12/13 was obtained (Scheme 5). The first example of a [Co2(CO)6]‐induced highly stereoselective ene reaction is described. To account for these results, the formation of intermediates are proposed (Schemes 6 and 7) which hitherto have not been considered in the mechanistic description of the Pauson‐Khand reaction.
Synthesis of 1,6‐Dideoxynojirimycin, 1,6‐Dideoxy‐D‐allo‐nojirimycin, and 1,6‐Dideoxy‐D‐gulo‐nojirimycin via Asymmetric Hetero‐Diels‐Alder Reactions
Authors: Defoin Albert , Sarazin Hervé , Streith Jacques
Published: December 2004

Asymmetric Diels‐Alder reaction of sorbaldehyde O‐methyloxime 1d with chiral chloronitroso derivative 2 of D‐mannose, followed by osmylation of the primary cycloadduct, led to diol 6a with excellent enantioselectivity (ee > 99%; Scheme 1). Catalytic hydrogenolysis of 6a gave 1,6‐dideoxy‐D‐allo‐nojirimycin (7a). Nucleophilic ring opening of cyclic sulfate 8 allowed a straightforward synthesis of 1,6‐dideoxynojirimycin (11) and of 1,6‐dideoxy‐D‐gulo‐nojirimycin (12; Scheme 2).
Anion Cryptates: Synthesis, Crystal Structures, and Complexation Constants of Fluoride and Chloride Inclusion Complexes of Polyammonium Macrobicyclic Ligands
Authors: Dietrich Bernard , Dilworth Brid , Lehn Jean‐Marie , Souchez Jean‐Paul , Cesario Michèle , Guilhem Jean , Pascard Claudine
Published: December 2004

Three macrobicyclic octamines 1–3 and the macrotricyclic hexadecamine 14 have been synthesized. The octamines 1–3 bind anionic substrates when protonated. The stability constants of the complexes between the protonated forms of the macrobicyclic polyamines and halide anions have been determined by pH‐metric measurements. The stability constants in H2O are very high; 1 in its hexaprotonated form binds F− with high selectivity (selectivity F−/Cl− > 108), while 3 exhibits strong stability constants for both F− and Cl−. Three X‐ray structures have been obtained, one where F− is held inside the cavity of 1 · 6H+, one where Cl− is included in 3 · 6H+, and 3 · 6H+ where the cavity is empty.
Perrhenat‐katalysierte Umlagerung von Ethinyl‐β‐ionol
Authors: Arnold Wolf , Bonrath Werner , Pernin Renaud , Thum Andreas
Published: December 2004

Perrhenate‐Catalyzed Rearrangement of Ethinyl‐β‐ionol

The rearrangement of 2‐ethinyl‐β‐ionol (1) to α,β‐unsaturated carbonyl compounds using tetraalkylammonium perrhenate catalysts was studied. It was found that the Rupe‐Kambli product, ketone 2, is the main product (ca. 70%) of this rearrangement. The by‐product 4 (ca. 15%) is formed in a ring‐closure reaction.
The Active Centres of Agelastatin A, a Strongly Cytotoxic Alkaloid of the Coral Sea Axinellid Sponge Agelas dendromorpha, as Determined by Comparative Bioassays with Semisynthetic Derivatives
Authors: D'Ambrosio Michele , Guerriero Antonio , Pietra Francesco , Ripamonti Marina , Debitus Cécile , Waikedre Jean
Published: December 2004

Agelastatin A (1), an unusual alkaloid of the axinellid sponge Agelas dendromorpha from the Coral Sea, can be selectively acetylated (→7) or methylated at OHC(8a) (→4), peracetylated (→8) or permethylated at OHC(8a), NH(5), and NH(6) (→5), or, finally, subjected to C(9)C(8a) (→14) or C(5b)C(8a) β‐elimination (→11–13), in a regiospecific manner or not, depending on the reaction conditions. Under acidic conditions, compound 12 adds H2O or MeOH, regioselectively though not endo/exo stereoselectively, giving transoid/cisoid mixtures 1/18 or 4/19, respectively. Similarly 11 or 13 add MeOH to give mixtures (−)‐2/20 or 15/16, respectively. Compound 13 also adds AcOH giving mixture 8/17. The intermediate cisoid form obtained on treatment of 21 with H3O+ undergoes N(5)N(6) bridging affording pentacyclic 22 which constitutes a proof for the cisoid configuration. From conformational studies, rules are devised that allow assigning the configuration of these compounds from NMR data. In vitro comparative cytotoxicity assays of these compounds show that for high cytotoxic activity, such as of 1 in vivo, unsubstituted OHC(8a), HN(5), HN(6) moieties are needed in the natural B/D transoid configuration.
Computations of 57Fe‐NMR Chemical Shifts with the SOS‐DFPT Method
Authors: Bühl Michael , Malkina Olga L. , Malkin Vladimir G.
Published: December 2004

57Fe Shielding tensors of substituted iron‐carbonyl complexes have been computed employing the density‐functional‐based SOS‐DFPT method (sum‐over‐states density‐functional perturbation theory) with the IGLO (individual gauge for localized orbitals) choice of gauge origins and with large basis sets. The shieldings computed for [Fe(CO)5], [Fe(CO)3(H2CCHCHCH2)], [Fe(CO)3(cyclo‐C4H4)], [Fe(CO)4(H2CCHOMe)], [Fe(CO)4(H2CCHCN)], [Fe(CO)3(H2CCHCHO)], and [Fe(CO)2(C5H5)R] (R = Me, Bu, i‐Pr) correlate with the experimental δ(57Fe) values. However, the slope of the correlation line is 0.55 instead of 1, i.e., only about one half of the substituent effects on σ(Fe) is recovered in the calculations. Nearest‐neighbor effects appear to be described qualitatively (cf. in the [Fe(CO)2(C5H5)R] series, whereas effects of more remote substituents, e.g., for [Fe(CO)4(H2CCHX)] (X = MeO and CN)) are not reproduced. Dissociation energies of these species are discussed because of their relevance to experimental rate constants for substitution processes which are known to correlate with δ(57Fe). Even though the δ(13C) and δ(1H) data of ferrocene (7) are well reproduced theoretically, the computed σ(Fe) shielding of 7 deviates substantially from the σ(calc.)/δ(expt.) correlation, possibly indicating additional shortcomings in the theoretical description of this molecule.
Synthesis, and Solution and Solid‐State Structures of (η3‐Allyl){(4S)‐4‐benzyl‐2‐[2′‐(diphenylphosphino)phenyl]‐ 4,5‐dihydrooxazole‐P,N}palladium(II) Hexafluorophosphates. Comparison with Dichloro{(4S)‐2‐[2′‐(diphenylphosphino)phenyl]‐4,5‐dihydro‐4‐phenyloxazole‐P,N}zinc(II)
Authors: Baltzer Natalie , Macko Ludwig , Schaffner Silvia , Zehnder Margareta
Published: December 2004

Crystal and solution structures of the [PdII(η3‐allyl)] and of the [PdII(η3‐1,3‐diphenylallyl)] complexes, 4 and 5, respectively, with (4S)‐4‐benzyl‐2‐[2′‐(diphenylphosphino)phenyl]‐4,5‐dihydrooxazole (3) were determined by X‐ray crystallography and 2D‐NMR spectroscopy. Complex 4 proved to be disordered with both diastereoisomeric complexes in the crystal. The results of X‐ray and NMR experiments demonstrate a good agreement between solution and solid‐state equilibria of the two isomers. A comparison with dichloro{(4S)‐2‐[2′‐(diphenylphosphino)phenyl]‐4,5‐dihydro‐4‐phenyloxazole‐P,N}zinc(II) (2b) shows a surprising conformational stability of the coordinated phosphinooxazole ligand 3.
An Analysis of the Bonding Properties of Benz[a]azulene by X‐Ray, NMR, and Computational Studies
Authors: Bühl Michael , Koźmiński Wiktor , Linden Anthony , Nanz Daniel , Sperandio David , Hansen Hans‐Jürgen
Published: December 2004

The X‐ray crystal structures of 9‐phenylbenz[a]azulene (4) and the corresponding non‐benzannelated form, 4‐phenylazulene (5), have been determined (cf. Fig.2). In contrast to 5, the skeleton of which shows nearly equal C,C bond lengths (cf. Table 1), the seven‐membered ring of 4 exhibits clearly alternating C,C bond lengths (cf. Table 1). This is in agreement with a strong accentuation of the heptafulvene substructure in 4 by the [a] benzannelation. The alternating bond lengths of 4 and of its parent structure 3 are also reflected in the corresponding variations of the 3J(H,H) and 1J(13C,13C) values of these benz[a]azulenes (cf. Tables 4 and 5). Computations on the MP2/6‐31G* level as well as on the BP86/6‐31G* level for azulene (6), benz[a]azulene (3), and heptafulvene (7) are in good agreement with the experimental values (cf. Tables 6–8).
Total Synthesis of (+)‐(8S,13R)‐Cyclocelabenzine
Authors: Schultz Katja , Hesse Manfred
Published: December 2004

An asymmetric synthesis of the spermidine alkaloid (+)‐cyclocelabenzine (1a) and its (−)‐(13S)‐epimer 1b is described using optically active (+)‐(3S)‐3‐amino‐3‐phenylpropionic acid as the chiral building block. The isoquinolin‐1‐one fragment 15 was synthesized by a modified Bischler‐Napieralski reaction. The relative configuration of the (−)‐isomer was determined by an X‐ray crystal‐structure analysis, which enabled us to determine the absolute configuration of natural (+)‐1a as (8S,13R).
Three‐Component Reactions with Sterically Crowded 2,2,4,4‐Tetramethyl‐3‐thioxocyclobutanone, Phenyl Azide, and Electron‐Deficient C,C‐Dipolarophiles
Authors: Mlostoń Grzegorz , Romańnski Jaroslaw , Linden Anthony , Heimgartner Heinz
Published: December 2004

In order to trap ‘thiocarbonyl‐aminides’ A, formed as intermediates in the reaction of thiocarbonyl compounds with phenyl azide, a mixture of 2,2,4,4‐tetramethyl‐3‐thioxocyclobutanone (1), phenyl azide, and fumarodinitrile (8) was heated to 80° until evolution of N2 ceased. Two interception products of the ‘thiocarbonylaminide’ A (ArPh) were formed: the known 1,4,2‐dithiazolidine 3 (cf. Scheme 1) and the new 1,2‐thiazolidine 12 (Scheme 2). The structure of the latter was established by X‐ray crystallography (Fig.1). The analogous ‘three‐component reaction’ with dimethyl fumarate (9) yielded, instead of 8, in addition to the known interception products 3 and 6 (Scheme 1), two unexpected products 15 and 16 (Scheme 3), of which the structures were elucidated by X‐ray crystallography (Fig.2). Their formation is rationalized by a primary [2 + 3] cycloaddition of diazo compound 18 with 1 to give 19, followed by a cascade of further reactions (Scheme 4).
Synthesis, Conformational Properties, and Synthetic Applications of Novel Optically Pure α,α‐Disubstituted (R)‐ and (S)‐Glycines (‘α‐Chimeras’) Combining Side Chains of Asp, Glu, Leu, Phe, Ser, and Val
Authors: Obrecht Daniel , Abrecht Christine , Altorfer Michael , Bohdal Udo , Grieder Alfred , Kleber Martina , Pfyffer Patrick , Müller Klaus
Published: December 2004

A series of novel open‐chain and cyclic conformationally constrained α,α‐disubstituted (R)‐ and (S)‐glycine derivatives (‘α‐chimeras’) combining side chains of Asp, Glu, Leu, Phe, Ser, and Val have been efficiently synthesized by using α‐alkylation of racemic 4‐monosubstituted 2‐phenyl‐1,3‐oxazol‐5(4H)‐ones of type 5, resolution after reaction with (S)‐phenylalanine cyclohexylamide (8) as chiral auxiliary, a novel azlactone/dihydrooxazole interconversion reaction to synthesize optically pure α‐substituted (R)‐ and (S)‐serine derivatives coupled with succinimide‐ring formation of aspartic‐acid derivatives. Based on X‐ray structures of (R,S)‐9b, (R,S)‐11c, (R,S)‐18, and (S,S)‐30, the absolute configuration of these novel amino‐acid building blocks could be unambiguously determined and their preferred conformations in the crystalline state be assessed. The high preference of the open‐chain derivatives (R,S)‐1, (S,S)‐3, and (R,S)‐11c for β‐turn type‐I conformations, as well as of the succinimide derivatives (R,S)‐2, (S,S)‐19, (S,S)‐24, (S,S,S)‐26, and (R,S)‐29 for β‐turn type‐II conformations and of (S,S)‐4, (R,S)‐18, (R,S)‐23, and (S,S)‐30 for β‐turn type‐II′ conformations could be confirmed in solution by using CD and NMR spectroscopy. Finally, the spiro derivatives (R,S)‐29 and (S,S)‐30 incorporating the ‘α‐chimera’ of Asp/Glu constitute doubly constrained peptide building blocks combining the properties of α‐substituted prolines and aspartimides.
Polymer‐ and Dendrimer‐Bound Ti‐TADDOLates in Catalytic (and Stoichiometric) Enantioselective Reactions: Are pentacoordinate cationic Ti complexes the catalytically active species?
Authors: Seebach Dieter , Marti Roger E. , Hintermann Tobias
Published: December 2004

α,α,α′,α′‐Tetraaryl‐1,3‐dioxolane‐4,5‐dimethanols (TADDOLs), containing styryl groups either at C(2) of the heterocyclic ring or in the α‐position, were prepared in the usual way (18–22, 24, 25). These compounds were copolymerized with styrene and divinylbenzene in a suspension, yielding polymers (33–40, Scheme 3) as beads with a rather uniform particle‐size distribution (150–45 μm), swellable in common organic solvents. HOCH2‐ and BrCH2‐substituted TADDOLs were also prepared and used for attachement to Merrifield resin or to dendritic molecules (23, 26–32). The TADDOL moieties in these materials are accessible to form Ti (and Al) complexes (Scheme 4) which can be used as polymer‐ or dendrimer‐bound reagents (stoichiometric) or Lewis acids (catalytic). The reactions studied with these new chiral auxiliaries are: enantioselective nucleophilic additions to aldehydes (of R2Zn and RTi(OCHMe2)3; Scheme 5, Table 1) and to ketones (of LiAlH4, Table 2); enantioselective ring opening of meso‐anhydrides (Scheme 6); [4+2] and [3+2] cycloadditions of 3‐crotonyl‐1,3‐oxazolidin‐2‐one to cyclopentadiene and to (Z)‐N‐benzylidenephenylamine N‐oxide ( → 48, 49, Scheme 7, Tables 3, 4, and Fig. 5). The enantioselectivities reached with most of the polymer‐bound or dendritic TADDOL ligands were comparable or identical to those observed with the soluble analogs. The activity of the polymer‐bound Lewis acids was only slightly reduced as compared with that encountered under homogeneous conditions. Multiple use of the beads (up to 10 times), without decreased performance, has been demonstrated (Figs. 3 and 4). The poorer selectivity in the Diels‐Alder reaction (Scheme 7a), induced by the polymer‐bound Cl2Ti‐TADDOLate as compared to the soluble one, is taken as an opportunity to discuss the mechanism of this Lewis‐acid catalysis, and to propose a cationic, trigonal‐bipyramidal complex as the catalytically active species (Fig. 6). It is suggested that similar cations may be involved in other Ti‐TADDOLate‐mediated reactions as well.
The First Asymmetric Intramolecular Stetter Reaction. Preliminary Communication
Authors: Enders Dieter , Breuer Klaus , Runsink Jan , Teles J. Henrique
Published: December 2004

The first asymmetric intramolecular Stetter reaction is reported, using the chiral triazolium salt 1 as catalyst. Starting from the easily accessible 4‐(2‐formylphenoxy)but‐2‐enoates 2, this protocol opens up an enantioselective pathway to the benzo‐annulated pyran‐4‐ones (chroman‐4‐ones) 3a–h with good yields and enantiomeric excesses of up to 74%.
Hydrolytical Cleavage of TAR‐RNA, the trans‐Activation Responsive Region of HIV‐1, by a Bis(guanidinium) Catalyst Attached to Arginine
Authors: Kurz Kristina , Göbel Michael W.
Published: December 2004

Guanidinium compounds imitating the bis(arginine) structural motif of staphylococcal nuclease (e.g. 3) are known to be powerful catalysts for phosphoryl transfer reactions in dipolar aprotic solvents. Compound 3 also accelerates the hydrolysis of RNA (H2O, pH 7). However, due to diminished substrate affinity in H2O, the rate effects are less pronounced in aqueous than in aprotic solution. To test if a synthetic ribonuclease may be derived from the bis(guanidinium) moiety of 3 by the addition of RNA‐binding substructures, the TAR sequence of HIV‐1 was chosen as a target. The arginine residue of compound 4 serves as an extremely simplified mimic of tat, a protein responsible for boosting the viral transcription by complex formation with TAR. Here, we present the synthesis of 4 and its ability to bind and to cleave efficiently the truncated TAR sequence 1. In addition, the synthesis of an acridine arginine conjugate, 19, is reported in preliminary form. Compound 19 associates with 1 and completely blocks the cleavage induced by 4.
Electrospray‐Ionization Mass Spectrometry. Part III. Acid‐Catalyzed Isomerization of N,N′‐Bis[(E)‐3‐(4‐hydroxyphenyl)prop‐2‐enoyl]spermidines by the Zip Reaction
Authors: Bigler Laurent , Schnider Christian F. , Hu Wenqing , Hesse Manfred
Published: December 2004

The electrospray tandem mass spectra (ESI‐MS/MS) of the three N,N′‐bis[(E)‐3‐(4‐hydroxyphenyl)prop‐2‐enoyl]spermidines 1–3 displayed the same fragment‐ion signals. These isomers could not be differentiated by ESI‐MS/MS, since their fragmentation patterns are similar. (E,E)‐N‐(3‐[15N]Aminopropyl)‐3,3′‐bis(4‐ hydroxyphenyl)‐N,N′‐(butane‐1,4‐diyl)bis[prop‐2‐enamide] ([15N(1)])‐(1) was synthesized in order to get further information about the fragmentation mechanisms. The comparison of the ESI‐MS/MS of 1 and [15N(1)]‐1 revealed a transamidation, the Zip reaction, under mass‐spectral conditions of the [1 + H]+ ions. Because of this reaction, the three isomers 1–3 could not be distinguished.
Synthesis of Fused Triazoles as Probes for the Active Site of Retaining β‐Glycosidases: From Which Direction Is the Glycoside Protonated?
Authors: Heightman Tom D. , Locatelli Monica , Vasella Andrea
Published: December 2004

The structure of the β‐glycosidase inhibitors 1–7 and 10–13 suggests that protonation of O–C(1) (the glycosidic O‐center) of the substrate by a carboxy group of the retaining β‐glycosidases does not occur in the plane perpendicular to the ring of the glycon (β‐side; ‘from the top’), but in the plane of the ring (‘from the side’). The triazoles 17 and 18 have been prepared in six steps from the L‐xylofuranose 21. They possess a CH group instead of the N‐center of the related tetrazoles 4 and 5, corresponding to the glycosidic O‐atom, and a very similar structure, both in solution and in the solid state. Unlike the tetrazoles, however, which are good‐to‐medium inhibitors of retaining β‐glycosidases, the triazoles do not inhibit the β‐glycosidases from sweet almonds, snail, and bovine liver, and only slightly inhibit the β‐glucosidase from Caldocellum saccharolyticum. This is in keeping with the proposed direction of protonation in the plane of the saccharide ring and with modelling studies, docking 4 into the active site of the white clover cyanogenic β‐glucosidase and 6 into the E. coli β‐galactosidase and the Lactococcus lactis 6‐phospho‐β‐galactosidase.
Double‐Bond Shifts in [4n]Annulenes as a New Principle for Molecular Switches: First Results with Dimethyl Heptalene‐1,2‐ and ‐4,5‐dicarboxylates
Authors: Briquet Anne Andrée Sophie , Uebelhart Peter , Hansen Hans‐Jürgen
Published: December 2004

A new concept for molecular switches, based on thermal or photochemical double‐bond shifts (DBS) in [4n]annulenes such as heptalenes or cyclooctatetraenes, is introduced (cf. Scheme 2). Several heptalene‐1,2‐ and ‐4,5‐dicarboxylates (cf. Scheme 4) with (E)‐styryl and Ph groups at C(5) and C(1), or C(4) and C(2), respectively, have been investigated. Several X‐ray crystal‐structure analyses (cf. Figs. 1–5) showed that the (E)‐styryl group occupies in the crystals an almost perfect s‐trans‐conformation with respect to the CC bond of the (E)‐styryl moiety and the adjacent CC bond of the heptalene core. Supplementary 1H‐NOE measurements showed that the s‐trans‐conformations are also adopted in solution (cf. Schemes 6 and 9). Therefore, the DBS process in heptalenes (cf. Schemes 5 and 8) is always accompanied by a 180° torsion of the (E)‐styryl group with respect to its adjacent CC bond of the heptalene core. The UV/VIS spectra of the heptalene‐1,2‐ and ‐4,5‐dicarboxylates illustrated that it can indeed be differentiated between an ‘off‐state’, which possesses no ‘through‐conjugation’ of the π‐donor substituent and the corresponding MeOCO group and an ‘on‐state’ where this ‘through‐conjugation’ is realized. The ‘through‐conjugation’, i.e., conjugative interaction via the involved s‐cis‐butadiene substructure of the heptalene skeleton, is indicated by a strong enhancement of the intensities of the heptalene absorption bands I and II (cf. Tables 3–6). The most impressive examples are the heptalene‐dicarboxylates 11a, representing the off‐state, and 11b which stands for the on‐state (cf. Fig.8).
Pyranosyl‐RNA (‘p‐RNA’): NMR and Molecular‐Dynamics Study of the Duplex Formed by Self‐pairing of Ribopyranosyl‐(C‐G‐A‐A‐T‐T‐C‐G)
Authors: Schlönvogt Irene , Pitsch Stefan , Lesueur Catherine , Eschenmoser Albert , Jaun Bernhard , Wolf Romain M.
Published: December 2004

The solution structure of the duplex formed by self‐pairing of the p‐RNA octamer β‐D‐ribopyranosyl‐(2′→4′)‐(CGAATTCG) was studied by NMR techniques and, independently, by molecular‐dynamics calculations. The resonances of all non‐exchanging protons, H‐bearing C‐atoms, P‐atoms, and of most NH protons were assigned. Dihedral angle and distance constraints derived from coupling constants and NOESY spectra are consistent with a single dominant conformer and corroborate the main structural features predicted by qualitative conformational analysis. The duplex displays Watson‐Crick pairing with antiparallel strand orientation. The dihedral angles β and ϵ in the phosphodiester linkages differ considerably from the idealized values. Model considerations indicate that these deviations from the idealized model allow better interstrand stacking and lessen unfavorable interactions in the backbone. The average base‐pair axis forms an angle of ca. 40° with the backbone. The resulting interstrand π‐π stacking between either two purines, or a purine and a pyrimidine, but not between two pyrimidines, constitutes a characteristic structural feature of the p‐RNA duplex. A 1000‐ps molecular‐dynamics (MD) calculation with the AMBER force field resulted in an average structure of the same conformation type as derived by NMR. For the backbone torsion angle ϵ, dynamically averaged coupling constants from the MD calculation agree well with the experimental values, but for the angle β, a systematic difference of ca. 25° remains. The two base pairs at the ends of the duplex are calculated to be highly labile, which is consistent with the high exchange rate of the corresponding imino protons found by NMR.