bluuebunny/crossref_metadata_2025 huggingface dataset:
Conformational Analysis of the cis‐ and trans‐Isomers of FK506 by NMR and Molecular Dynamics
Authors: Mierke Dale F. , Schmieder Peter , Karuso Peter , Kessler Horst
Published: December 2004

The potent immunosuppressant drug FK506 (2) has been examined by 1H‐ and 13C‐NMR spectroscopy and NOE‐restrained molecular dynamics to elucidate the conformation in solution. A combination of two‐ and three‐dimensional NMR techniques was used to completely assign the 1H‐ and 13C‐NMR chemical shifts of the two configurational isomers resulting from the cis‐trans isomerization about the single amide bond. Hetero‐ and homonuclear coupling constants were measured to assign the diastereotopic methylene protons at C(16), C(18), and C(23). Intramolecular HH distances were defined from NOESY spectra recorded at −30° in CDCl3 and used as constraints in molecular‐dynamics simulations. The conformational preferences of 2 in solution are discussed in light of the constitutional features recently proposed to be necessary for binding and activity.
α‐Methylidene‐ and α‐Alkylidene‐β‐lactams from Nonproteinogenic Amino Acids
Authors: Buchholz Rainer , Hoffmann H. Martin R.
Published: December 2004

Treatment of methyl 2‐(1‐hydroxyalkyl)prop‐2‐enoates 1 with conc. HBr solution afforded methyl (Z)‐2‐(bromomethyl)alk‐2‐enoates 2, which were transformed regioselectively into N‐substituted methyl (E)‐2‐ (aminomethyl)alk‐2‐enoates 3 (SN2 reaction) and into N‐substituted methyl 2‐(1‐aminoalkyl)prop‐2‐enoates 4(SN2′ reaction). Regiocontrol of nucleophilic attack by amine was accomplished simply by choice of solvent, the SN2 reaction occurring in MeCN and the SN2′ reaction in petroleum ether. Hydrolysis and lactamization afforded β‐lactams 7 and 8, containing an exocyciic alkylidene and methylidene group at C(3), respectively.
Synthese von ‘Push‐Pull’‐Oligoacetylenen
Authors: Bartlome Andreas , Stämpfli Urs , Neuenschwander Markus
Published: December 2004

Synthesis of ‘Push‐Pull’‐OligoAcetylenes

‘Push‐pull’ triacetylenes 11a, b, c, as well as ‘push‐pull’ tetraacetylene 13b have been prepared by reaction of the corresponding trichloroene(oligoinyl)amines 9 and 10 with 2 mol‐equiv. of BuLi followed by acylation. The sequences (Schemes 3 and 4) are very simple and straightforward, they could in principle be applied to the synthesis of ‘push‐pull’ pentaAcetylenes 15 and hexaacetylenes 17 (Scheme 5). Main limitations are the moderate yields as well as the low thermal stability of push‐pull oligoacetylenes.
High‐Resolution Solid‐State MAS13C‐ and 1H‐NMR Spectra of Benzenoid Aromatics Adsorbed on Alumina and Silica: Successful Applications of 1D and 2D Pulse Experiments from Liquid‐State NMR
Authors: Ebener Michael , Fircks Gero Von , Günther Harald
Published: December 2004

Strong line‐narrowing effects in solid‐state, magic‐angle‐spinning (MAS) 13C‐ as well as 1H‐NMR spectra of benzenoid aromatics adsorbed at alumina or silica surfAccs indicate high mobility of the organic adsorbates. Even under modest spinning rales (1 kHz), dipolar couplings are sufficiently reduced to allow scalar 13C,1H couplings to be measured. Hetero‐ and homonuclear pulse sequences known from high‐resolution NMR in liquids, like SEFT, J‐RESOLVED, DEPT, COSY, and 13C,1H shift‐correlation experiments are successfully applicable. 13C spin‐lattice relaxation limes are as short as 0.5 s (CH) and 1.1 s (Cq), and T1(1H) values are in the order of 0.3 s.
Gas‐Phase Chemistry of Ti+ to Zn+ with Butyl Isothiocyanate
Authors: Eller Karsten , Akkök Semiha , Schwarz Helmut
Published: December 2004

Using a complete set of 2H‐labeled isotopomers, the gas‐phase reactions of Ti+ to Zn+ with butyl isothio‐cyanate are studied. The main product for most of the metal ions is MHNCS+ formed by an ion/dipole mechanism. Exceptions are Cr+, which yields significant amounts of H2 and H2S loss, Mn+, which is the only ion that does not form MHNCS+ at all but produces mainly C2H4 and C3H6, and Zn+, which predominantly reacts by charge transfer.
Preparative Resolution of Heterocyclic Acetals Derived from Glycine, Mercapto‐acetic Acid, β‐Alanine, and Formyl‐ or Acetylacetic Acid by Recycling Chromatography onChiraspherand Temperature Dependence of Separation Factors
Authors: Kinkel Joachim N. , Gysel Urs , Blaser Denis , Seebach Dieter
Published: December 2004

Chiraspher, a polymer of ethylN‐acryloylphenylalanine on spherical silica gel, is used for the preparative separation by recycling chromatography of the enantiomers of oxazolidinonesrac‐5, thioxolanonerac‐6, per‐hydropyrimidinonerac‐7, and dioxinonesrac‐9and10derived from the acids listed in the title (Figs.1–5). The oxazolidinonesrac‐1a,‐2, and‐4show a peculiar peak of the separation efficiences upon lowering theChiraspher‐column temperature to 15° (Fig.6). In some cases, multigram amounts of enantiomerically pure heterocycles could thus be prepared. The absolute configurations of most enantiomers are assigned. First applications of thetert‐butyl 5‐oxo‐2‐phenyloxazolidine‐3‐carboxylate (5) as a nucleophilic chiral glycine building block are described (products13–16,Scheme 2). A list of enantiomerically pure 1,3‐dioxinones is presented (Table 1), showing a correlation between their absolute configuration, sense of optical rotation, and elution behavior onChiraspher.
Studies for a Diastereoselective Synthesis of the Tetracyclic Diterpenic Diol Stemarin: A Model Study for a New Preparation of the Key Intermediate and the Synthesis of (+)‐18‐Deoxystemarin
Authors: Berettoni Marco , Bettolo Rinaldo Marini , Montanari Vittorio , Prencipe Teresa , Romeo Sergio
Published: December 2004

Methods for a stereoselective preparation of compounds of type 2b, a key intermediate of a previous synthesis of the tetracyclic diterpene stemarin (la), have been tested on model compounds 5a, 5c, and 8a. Thus, (±)‐(1RS,6SR,8SR,11SR)‐hydroxytricyclo[6.2.2.0l,6]dodecan‐9‐one (5a) was transformed by the Mitsunobu reaction into (±)‐(1RS,6SR,8SR,11RS)‐11‐(benzoyloxy)tricyclot[6.2.2.01,6]dodecan‐9‐one (6b; Scheme 2). The latter was also obtained from (±)‐(1RS,6SR,8SR,11RS)‐11‐[(4)‐toluenesulfonyloxy]tricyclo[6.2.2.01,6]dodecan‐9‐one (5c) by the action of Et4N (PhCOO) in acetone. Compound 6b was then converted into (±)‐(1RS,6RS,8RS,9RS)‐tricyclo[6.2.2.01,6]dodecan‐9‐ol (8b), a model for 2b. Compound 8b was also prepared from its epimer 8a by the Mitsunobu reaction via ester 7b. The inversion of configuration of bicyclo[2.2.2]octan‐2‐ols or derivates was not previously described. The model studies paved the way to the diastereoselective synthesis of (+)‐18‐deoxystemarin (1b) via 12β‐hydroxy‐13‐methyl‐9β,13β‐ethano‐9β‐podocarpan‐15‐one (10a) and 13‐methyl‐9β,13β‐ethano‐9β‐podpcarpan‐12α‐ol (11b).
Coenzyme F430 from Methanogenic Bacteria: Detection of a Paramagnetic Methylnickel(II) Derivative of the Pentamethyl Ester by 2H‐NMR Spectroscopy
Authors: Lin Shu‐Kun , Jaun Bernhard
Published: December 2004

A methylnickel(II) derivative of coenzyme F430 (1) was proposed as an intermediate in the enzymic process catalyzed by methyl‐CoM reductasc. Indirect evidence points to formation of CH3–F430MII in the reaction of F30M1 (obtained from F430MII (2)) with eleclrophilic methyl donors. The results presented here show, that such a compound does exist. A paramagnetic CD3–NiII derivative 5b of the pentamethyl ester 2 (F430M) of coenzyme F430 was prepared by in situ methylation with (CD3)2Mg and characterized by its isotropically shifted 2H‐NMR spectrum. At −40°, the very broad D‐signal of the axially coordinated CD3 group is found at −490 ppm. Comparison with the 2H‐ and 1H‐NMR spectra of mcthyl(tetramethylcyclam)nickel(II) derivatives 4 ([NiII(CH3))(tmc)]CF3SO3 (4a) is the only isolated CH3–Ni derivative of a N4macrocyclic NiII complex' shows that the large isotropic shift to high field is characteristic for a Me group axially bound to the Ni center. The temperature dependence of the isotropic shift of the CD3–Ni group in both 4b and 5b follows Curie's law and yields 2H hyperfine coupling constants of −0.65 (4b) and −0.85 MHz (5b), respectively. The 1H‐NMR spectrum indicates that, in contrast to the five‐coordinate monochloro complex [NiIICl(tmc)]+, intermolecular exchange of the axial ligand in [NiII(CH3)(tmc)]+ 4a is either slow at the NMR time scale or does not occur at all.
Isomerès optiques du naftidrofuryl ( = 2‐[(naphth‐1‐yl)méthyl]‐3‐(tétrahydrofur‐2‐yl)propanoate de 2‐(diéthylamino) éthyle)
Authors: Descours Denis , Festal Didier , Leger Jean‐Michel , Carpy Alain
Published: December 2004

Optical Isomers of Naftidrofuryl( = 2‐(Diethylamino)ethyl 2‐[(Naphth‐1‐yl)methyl]‐3‐(tetrahydrofur‐2‐yl)propanoate)

The four optical isomers of naftidrofuryl (1) were prepared in two ways, by separation and resolution of the two diastereoisomeric racemates and by synthesis from the enantiomers of tetrahydrofuran‐2‐methanol (6); see Scheme}. The absolute configuration of one of the isomer as a tartrate monohydrate was established by X‐ray crystallography thus allowing the deduction of the absolute configurations of the other three optical isomers.
Addition of Carbon Nucleophiles to Tricarbonylchromium Complexes of 1,2‐Dihydrocyclobutabenzene, Indane, 1,2,3,4‐Tetrahydronaphtbalene and ortho‐Xylene
Authors: Kündig E. Peter , Grivet Chantal , Wenger Eric , Bérnardinelli Gerald , Williams Alan F.
Published: December 2004

3‐Substituted 1,2‐dihydrocyclobutabenzenes (bicyclo[4. 2. 0]octa‐1,3,5‐triene) are readily accessible from [Cr(CO)3(1,2‐dihydrocyclobutabenzene)] (1) via a two‐step sequence which involves addition of a nucleophile and oxidation of the intermediate anionic cyclohexadienyl complex. Nucleophiles used include LiCMe2CN (A), LiCH2CN (B), LiC(Me)(OR)CN (C), (D), (E), LiCMe2CO2Me (F), and LiCH2CO2(t‐Bu) (G). [Cr(CO)3(Indane)] (2) also reacts highly regioselectively to give α‐substitution, whereas [Cr(CO)3(tetrahydronaphthalene)] (3) and [Cr(CO)3(o‐xylene)] (4) give mixtures of products. In several cases, the mixtures of the intermediate anionic cyclohexadienyl complexes can be equilibrated to give, after oxidation, β‐substituted derivatives of 1,2,3,4‐tetrahydronaphthalene and ortho‐xylene selectively. EHMO calculations were carried out, and they rationalize the observed α‐regioselectivity of nucleophilic addition under kinetic control, The X‐ray structures of 1 and 4 are reported and in both compounds the Cr(CO)3 group adopts in the solid state a staggered syn‐conformation with respect to the substituted aromatic C‐atonis.
Glycosylidene Carbenes. Part 5. Synthesis of Glycono‐1,5‐lactone Tosylhydrazones as Precursors of Glycosylidene Carbenes
Authors: Mangholz Sissi E. , Vaseha Andrea
Published: December 2004

The benzyl‐ and the acyl‐protected glyconolactone tosylhydrazones 6, 9, 12, 16, and 19 (Scheme 1) were prepared in good yields by treating the hemiacetals 4, 7, 10, 14, and 17 with N‐tosylhydrazine, to give the N‐glycosylhydrazines 5, 8,11,15, and 18, and by oxidizing these hydraz tries with N‐bromosuccinimide (NBS) in the presence of 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU), with CrO3–dipyridine complex or with pyridinium dichromate. Photolysis of the sodium sail 20 of 6 (Scheme 2) in the presence of N‐phenylmaleimide, dimethyl fumarate, or acrylonitrile gave the corresponding cyctopropanes 21–28 in satisfactory yields. Phololytic or thermolytic glycosidation of phenol and 4‐melhoxyphenol by 20 yielded the anomeric glycosides 29/30 and 31/32, yields being marginally higher for the Ihermolytic process. Phololytic glycosidation of propan‐2‐ol gave the glycosides 33 and 34 in low yields only. Yields and ratios of products were compared to those obtained with the diazirine 1 as a source of glycosylidene carbenes. While the yields from 20 are lower, the ratios of products obtained in the photolytic reactions are in agreement with the formation of a common intermediate from both carbene precursors.
Asymmetric Diels‐Alder Cycloadditions with Chiral Carbamoyl Dienophiles
Authors: Defoin Albert , Brouillard‐Poichet Agnès , Streith Jacques
Published: December 2004

Chiral acylnitroso dienophiles 14, which were obtained from L‐proline and from D‐mandelic acid, reacted with cyclohexa‐1,3‐diene to give the expected diastereoisomers 15 and 16 (Scheme 2 and Table 1). The d.e. values for these Diels‐Alder reactions were moderate; they are related to the molecular stiffness of the dienophiles. The absolute configuration of the major cycloadducts was interpreted in terms of HOMO/LUMO interactions, the approach being ‘endo’ and the acylintroso dienophiles reacting from their s‐cis‐conformation.
Catalytic asymmetric synthesis of Secondary (E)‐allyl alcohols from acetylenes and aldehydes via (1‐alkenyl)zinc intermediates. Preliminary Communication
Authors: Oppolzer Wolfgang , Radinov Rumen N.
Published: December 2004

Hydroboration of aliphatic 1‐alkynes with freshly prepared dicyclohexylborane (1 mol‐equiv., hexane), treatment of the resulting [(E)‐1‐alkenyl]boranes 5 with Et2Zn or Me2Zn (1.05 mol‐equiv.) followed by addition of (−)‐3‐exo‐(dimethylamino)isoborneol (DAIB, 8; 0.01 mol‐equiv.), subsequent addition of a solution of an aromatic or aliphatic aldehyde (1 mol‐equiv., hexane), and quenching with aq. NH4Cl provided (E)‐allyl alcohols 6 usually in 70–95% yield with 79–98% enantiomeric excess (Scheme 3 and Table).
Investigations of the Molecular Surface of a Few Sandalwood‐Odor Molecules and Related Structures: Conformational calculations on sandalwood odorants. VI
Authors: Buchbauer Gerhard , Leonhardsberger Karin , Winiwarter Susanne , Wolschann Peter
Published: December 2004

The calculated molecular surfaces for some Sandalwood‐odor molecules and structurally similar inactive compounds were compared with the calculated mean surface obtained from five Sandalwood odorants included in the set, and their individual agreement and deviations were estimated. Especially the investigation of selected parts of the surfaces seems very promising in finding structure subunits which might be important for an association to a possible receptor site.
Syntheses and X‐Ray Structures for Model Compounds of a Pyrimidinediyl‐Based Rigid‐Rod Aromatic Polyamide
Authors: Oertli Alfred G. , Meyer Werner R. , Suter Ulrich W. , Joho Felix B. , Gramlich Volker , Petter Walter
Published: December 2004

A variety of model compounds for the pyrimidinediyl‐based rigid‐rod polyamide poly[imino‐(pyrimidine‐2,5‐diyl)‐imino‐tetraphthaloyl] (PPYMT) was prepared, in order to compare their conformations to several model compounds of the related, fully aromatic polymer poly(p‐phenyleneterephthalamide) (PPTA). In particular, the structures of N‐(2‐pyrimidyl)benzamide (PYMB) and its complexed form bis[(N‐pyrimidin‐2‐yl)benzamide]nickel(II) dichloride (NiPYMB) were determined by X‐ray diffraction. The molecular packing in these crystals provides us with a model for the possible ‘cross‐linking’ of PPYMT fibers. The structures of the trimer model compounds N,N′ ‐bis(2‐pyrimidyl)terephthalamide (PYTA) and N,N′ ‐bis(benzoyl)‐2,5‐diaminopyrimidine (BDAP) yield information about the conformation of PPYMT chains and are compared to analogous model compounds of PPTA.
Multinuclear NMR Studies of Ligand‐Exchange Reactions on Analogous Technetium(V) and Rhenium(V) Complexes. Relevance to nuclear medicine
Authors: Helm Lothar , Deutsch Karen , Deutsch Edward A. , Merbach André E.
Published: December 2004

The kinetics of pyridine exchange on trans‐[MO2(py)4]+ have been followed by 1H‐NMR in CD3NO2 for M = Re, Tc: k298S−1 = (5.5 ± 0.1) × 10−6, 0.04 ± 0.02; ΔH≠/kJmol−1 = 111 ± 3, 101 ± 9; ΔS≠/JK−1mol−1 = +28 ± 10, +68 ± 35. For the Rev complex, pyridine and oxygen exchanges have been measured simultaneously by 1H‐ and 17O‐NMR in deuterated water: k298/s−1 = (8.6 ± 0.2) × 10−6 (py), (14.5 ± 0.3) × 10−6 (oxygen); ΔH≠/kJmol−1 = 111 ± 1, 91 ± 1; ΔS /JK−1mol−1 = +32 ± 3, −32 ± 4. For both complexes, the rate law for pyridine exchange is first‐order in complex and zero‐order in pyridine; together with the activation parameter values, and the fact that the rate does not depend significantly on the nature of the solvent, this strongly implies the operation of a dissociative mechanism. The ratio of pyridine exchange rates for the Tc and Re complexes at room temperature is ca. 8000. The consequences of these observations for radiopharmaceutical synthesis are discussed.
Cyclohexanecarboxylic‐Acid Derivatives from Psiadia trinervia
Authors: Wang Ying , Hamburger Matthias , Gueho Joseph , Hostettmann Kurt
Published: December 2004

From a MeOH extra of Psiadia trinervia, seven phenolic compounds were isolated by gel filtration and reversed‐phase chromatography. Six of them are known compounds, namely 3,4‐di‐O‐caffeoylquinic acid (2), 3,5‐di‐O‐caffeoylquinic acid (3), caffeic acid, and three 3‐methoxyflavonoids. Compound 1 is a 3,4‐di‐O‐caffeoyl derviative of (1S,3R,4R,5R)‐1,3,4, 5‐tetrahydroxycyclohexanecarboxylic acid, a novel steroisomer of (−)‐quinic acid. Following hydrolytic treatment of the MeOH extract, ethyl 3‐O‐caffeoylquinate (4), ethyl 3,4‐di‐O‐caffeoylquinate (5), and ethyl 3,5‐O‐caffeoylquinate (6) were isolated. The latter three compounds are artifacts. The configuration of 1‐3 was established by NMR and CD (exciton chirality method).
Electrochemical Oxidation of Ergolines
Authors: Seifert Karlheinz , Phuong Nguyen Minh , Vincent Beverly R.
Published: December 2004

An electrochemical procedure for the preparation of D‐3‐alkoxy‐halogen‐2,3‐dihydro‐6‐methyl‐2‐oxoergolines‐I is described.
Crystal Structure of Bis(η6‐mesitylene)iron(II) Hexafluorophosphate
Authors: Cameron T. Stanley , Linden Anthony , Sturge K. Craig , Zaworotko Michael J.
Published: December 2004

The crystal Structure of [Fe(η6‐mesitylene)2](PF6)2 (1) is reported. The Structure is intricately disordered with the Fe‐atom occupying an m3m cubic site, but nonetheless the conformation and bonding is confirmed. The structure is discussed in the general context of FeII sandwich complexes.
Absolute Configuration of 3‐Substituted 1‐Azabicyclo[2.2.1]heptanes
Authors: Boelsterli Jakob , Eggnauer Ursula , Pombo‐Villar Esteban , Weber Hans‐Peter , Walkinshaw Malcolm , Gould Robert O.
Published: December 2004

The l‐azabicyclo[2.2.1]heptan‐3‐exo‐ol (2) was resolved by fractional crystallisation of its hydrogen tartrate salts. The enantiomers (+)‐ and (−)‐2 were oxidised to the ketones (−)‐4 and (+)‐4, respectively (Scheme). CD spectroscopy suggested that (−)‐4 possesses the (1R,4S)‐configuration. This absolute configuration was confirmed by single‐crystal X‐ray diffraction of the derivative (+)‐(1R,4R)‐3‐(1,3‐dithian‐2‐ylidene)‐1‐azabicyclo [2.2.1]‐heptane ((+)‐5).
Synthesis of Multi‐O4‐phospho‐L‐tyrosine‐Containing Peptides
Authors: Bannwarth Willi , Kitas Eric A.
Published: December 2004

Multi‐O4‐phospho‐L‐tyrosine‐containing peptides can be synthesized by the global as well as the buildingblock approach. Thus, we prepared by both strategies the triphosphorylated and the three regioisomeric diphosphorylated insulin‐receptor‐(1142–1153)‐dodecapeptide derivatives 7 and 4–6, respectively, of the parent Thr‐Arg‐Asp‐Ile‐Tyr‐Glu‐Thr‐Asp‐Tyr‐Tyr‐Arg‐Lys (3). These phosphorylated peptides are valuable tools to study the regioselectivity of dephosphorylation by phosphatases.
Stereoselektive Synthese von (2S,6S)‐2,6‐Diaminoheptandisäure und von unsymmetrischen Derivaten der meso‐2,6‐Diaminoheptandisäure
Authors: Bold Guido , Allmendinger Thomas , Herold Peter , Moesch Luzia , Schär Hans‐Peter , Duthaler Rudolf O.
Published: December 2004

Stereoselective Synthesis of (2S,6S)‐2,6‐Diaminoheptanedioic Acid and of Unsymmetrical Derivatives of meso‐2,6‐Diaminoheptanedioic Acid

Specific inhibition of enzymes of the diaminopimelate pathway (L‐lysine biosynthesis) should, in principle, lead to selective antibacterial agents or herbicides. For this purpose, enantioselective syntheses were devised for (2S, 6S)‐2, 6‐diaminoheptanedioic acid (L, L‐diaminopimelate, 1), (2R,6S)‐2,6‐diamino‐2‐methylhept‐3‐enedioic acid (10), (2R, 6S)‐2, 6‐diaminohept‐3‐enedioic acid (9), (2R, 6S)‐2, 6‐diamino‐4‐fluorohept‐3‐enedioic acid (42), and (2S, 6S)‐2, 6‐diamino‐3‐chloroheptanedioic acid (5). The Schöllkopf bislactim‐ether methodology was applied to control the configuration of C(2) and C(6) of 1, C(2) of 10, as well as C(6) of 9 and 42. Semialdehyde derivatives of L‐glutamate afforded C(6) of 10 and 5, while the (R)‐configurated C(2) of 9 and 42 were derived from L‐serine. For this purpose, the synthesis of the Garner aldehyde 32 has been improved. As chromatographic purifications and the low temperatures for the reduction of the carboxylic acid are eliminated, this valuable intermediate can now be prepared in bulk quantities. An enantio‐ and diastereoselective aldol addition of a glycine titanium‐enolate was applied for the construction of 5 (C(2) and C(3)). As all chiral building blocks and reagents used are available in both enantiomeric forms, these routes should also be suitable for the selective synthesis of the other stereoisomers of these bis(α‐amino acids).
The 6Li,6Li‐INADEQUATE Experiment: A New Tool for 1D‐ and 2D‐NMR Studies of Organolithium Compounds
Authors: Eppers Oswald , Fox Thomas , Günther Harald
Published: December 2004

The 1D‐ and 2D‐6Li, 6Li‐INADEQUATE experiments are described as new tools for the detection of scalar coupled nonequivalent 6Li nuclei in organolithium clusters. Practical applications of these sequences are demonstrated for the 6Li‐NMR spectra of (E)‐1‐lithio‐2‐(2‐lithiophenyl)‐1‐phenylhex‐1‐ene (1) and (E)‐2‐lithio‐1‐(2‐lithiophenyl)‐1‐phenylpent‐1‐ene (2), where signals due to dimers and monomers can be distinguished. The performance of the 2D‐6Li, 6Li‐INADEQUATE and the 6Li, 6Li‐COSY‐45‐LR experiment are compared. The 6Li chemical shifts of 1 and 2 are discussed.
Synthese von 2‐substituierten und 2,3‐disubstituierten Alkyl‐ und Aryl‐thiophenen und 2,3‐anellierten Thiophen‐Derivaten aus Ketonen als C2‐Bausteine und Carbonodithiosäure‐O‐ethyl‐S‐(2‐oxoethyl)ester als C2S‐Baustein
Authors: Aldvogel Erwin
Published: December 2004

Synthesis of 2‐Substituted and 2,3‐Disubstituted Alkyl‐ und Aryl‐thiophenes and Related 2,3‐Anellated Thiophene Derivatives, Using Ketones and Carbonodithioic Acid O‐Ethyl S‐(2‐Oxoethyl) Ester as the Building Blocks

A simple method to synthesize 2‐substituted and 2,3‐disubstituted alkyl‐ and aryl‐thiophenes as well as related 2,3‐anellated thiophenes 6, starting from ketones 1 as C2‐fragment and the S‐protected carbonodithionic‐acid derivative 3 as a C2S‐fragment is described. The aldols 4 are intermediates of the two step process.
Structure and Reactivity of Five‐ and Six‐Ring N, N‐, N, O‐, and O, O‐acetals: A lesson in allylic 1, 3‐strain (A1, 3strain)
Authors: Seebach Dieter , Amatsch Bernd , Amstutz René , Beck Albert K. , Doler Max , Egli Martin , Fitzi Robert , Gautschi Markus , Herradön Bernardo , Hidber Pirmin C. , Irwin John J. , Locher Rita , Maestro Miguel , Maetzke Thomas , Mouriño Antoni , Pfammatter Elmar , Plattner Dietma A. , Schickli Christof , Schweizer W. Bernd , Seiler Paul , Stucky Gerhar , Petter Walter , Escalante Jaime , Juaristi Eusebio , Quintana Delia , Miravitlles Carlos , Molins Elies
Published: December 2004

The X‐ray structures of fifteen 1, 3‐imidazolidine, 1, 3‐oxazolidine, 1, 3‐dioxan‐4‐one, and hydropyrimidine‐4(1H)‐one derivatives are described (Table 2) and compared with known structures of similar compounds (Figs. 1–20). The differences between structures containing exocyclicN‐acyl groups and those lacking this structural element arise from the A1,3effect of the amide moieties. Event‐Bu groups are forced into axial positions of six‐ring half‐chair or into flag‐pole positions of six‐ring twist‐boat conformers by this effect (Figs. 16–20). In theN‐acylated five‐membered heterocycles, a combination of ring strain and A1, 3strain leads to strong pyramidalizations of the amide N‐atoms (Table 1) such that the acyl groups wind up on one side and the other substituents on the opposite side of the rings (Figs. 4–9andScheme 3). Thus, the acyl (protecting!) groups strongly contribute to the steric bias between the two faces of the rings. Observed, at first glance surprizing stereoselectivities of reactions of these heterocycles (Schemes 1and2) are interpreted (Scheme 3) as an indirect consequence of the amide A1, 3strain effect. The conclusions drawn are considered relvant for a better understanding of the ever increasing role which amide groups play in stereoselective syntheses.
Preparation of Campholenal Analogues: Chirons for the lipophilic moiety of sandalwood‐like odorant alcohols
Authors: Chapuis Christian , Brauchli Robert
Published: December 2004

In connection with structure‐activity relationship studies, analogues of campholenal ((+)‐4b), an important building block for sandalwood‐like odorants, were prepared. The five‐membered‐ring analogues 4 were obtained by epoxidation of the corresponding α‐pinene derivatives 2, followed by catalytic ZnBr2 isomerisation (Scheme 2). The six‐membered‐ring skeleton was obtained by ozonolysis of α‐campholenyl acetate ((−)‐14b), followed by intramolecular aldol condensation (Scheme 5). 13C‐NMR assignments are given.
New Heteroaromatic Complexing Agents and Luminescence of Their Europium(III) and Terbium(III) Chelates
Authors: Mukkala Veli‐Matti , Sund Christian , Kwiatkowski Marek , Pasanen Paavo , Högberg Marita , Kankare Jouko , Takalo Harri
Published: December 2004

Twelve heteroaromatic complexing agents 9a–I were synthesized with the purpose to develop suitable labels for time‐resolved luminescence‐based bioaffinity assays. The relative luminescence yields, excitation maxima, and emission decay constants of their europium(III) and terbium(III) chelates were determined. According to these results, 2,2′,2″,2‴‐[(2,2′‐bipyridine‐6,6′‐diyl)bis(methylenenitrilo)]tetrakis (acetic acid) (9e) and 2,2′,2″,2‴‐[(2,2′:6′,2″‐terpyridine‐6,6″‐diyl)bis(methylenenitrilo)] tetrakis(acetic acid) (91) are the most promising agents.
Conformational Analysis of 1,2:3,4‐Diepoxides: Ab Initio and semiempirical molecular‐orbital calculations
Authors: Nikles Martin , Bur Daniel , Séquin Urs , Huber Hanspeter
Published: December 2004

Using semiempirical and ab initio procedures, the most stable conformations of meso‐ and rac‐bioxirane and of some substituted 1,2:3,4‐diepoxides were calculated. For threo‐diepoxides (having the same relative configurations as rac‐bioxirane, 3), two stable conformations with CCCC dihedral angles of ca. 90 and ca. 270° were found. For erythro‐diepoxides (derivatives of meso‐bioxirane, 4) the calculations suggest three preferred conformations with corresponding dihedral CCCC angles of ca. 90°, ca. 180°, and ca. 270°. The calculations are in fair agreement with the experimental data available for the unsubstituted compounds 3 and 4.
A Complex Pyrrolo‐oxazinone and Its Iodo Derivative Isolated from a Tunicate
Authors: Yoshida Wesley Y. , Lee Kit K. , Carroll Anthony R. , Scheuer Paul J.
Published: December 2004

Two cytotoxic triphenylpyrrolo‐oxazinones were isolated from a tunicate and their structures elucidated by spectral methods. Lukianol A ( = 3,7,8‐tris(4‐hydroxyphenyl)pyrrolo[2,1‐c][1,4]oxazin‐1 (1H)‐one; 1) had MIC of 1 μg/ml in KB cytotoxicity tests; MIC value for 2 was 100 μg/ml.
Light‐Induced Cycloaddition of Furan and addition of methanol to a 4‐thiacyclohex‐2‐enone ( = 2,3‐dihydro‐4H‐thiin‐4‐one) and a 4‐thiacyclopent‐2‐enone ( = thiophen‐3(2H)‐one)
Authors: Kowalewski Ronald , Margaretha Paul
Published: December 2004

Irradiation of newly synthesized 2,2‐dimethyl‐2,3‐dihydro‐4H‐thiin‐4‐one (1) in furan affords the two [4 + 2] cycloadducts 3 and 4 and the [2 + 2] cycloadduct 5 in a 5:4:1 ratio (Scheme 1). Irradiation of 1 in MeOH gives a 3:2 mixture of 5‐ and 6‐methoxy‐2,2‐dimethylthian‐4‐ones 6 and 7. Irradiation in CD3OD affords the same (deuterated) adducts with the CD3O and D groups trans to each other, results compatible with cis‐addition of MeOH to a trans ‐configurated ground‐state enone. Irradiation of the same enone in furan/MeOH 1:1 gives only the furan cycloadducts 3–5 and no MeOH adducts, suggesting that furan interacts with the (excited) triplet enone before the deactivation of this species to a ground‐state (E)‐cyclohexenone, which then reacts with MeOH. On irradiation in furan, the corresponding five‐membered thiaenone, 2,2‐dimethylthiophen‐3(2H)‐one (2) affords only one, cis‐fused, [4 + 2] cycloadduct with ‘exo’‐configuration, i.e. 8, and 2 does not undergo solvent addition but rather cyclodimerization (→9) on irradiation in MeOH (Scheme 1).
Thermal Reaction of Highly Alkylated Azulenes with Dimethyl Acetylenedicarboxylate: HOMO(Azulene) vs. SHOMO(Azulene) Control in the Primary Thermal Addition Step
Authors: Chen Yi , Kunz Roland W. , Uebelhart Peter , Weber Roland H. , Hansen Hans‐JüRgen
Published: December 2004

The reaction of highly alkylated azulenes with dimethyl acetylenedicarboxylate (ADM) in decalin or tetralin at 180–200° yields, beside the expected heptalene‐ and azulene‐1,2‐dicarboxylates, tetracyclic compounds of type ‘anti’‐V and tricyclic compounds of type E (cf. Schemes 2–4 and 8–11). The compounds of type ‘anti’‐V represent Diels‐Alder adducts of the primary tricyclic intermediates A with ADM. In some cases, the tricyclic compounds of type E also underwent a consecutive Diels‐Alder reaction with ADM to yield the tetracyclic compounds of type ‘anti’‐ or ‘syn’‐VI (cf. Schemes 2 and 8–11). The tricyclic compounds of type E, namely 4 and 8, reversibly rearrange via [1,5]‐C shifts to isomeric tricyclic structures (cf. 18 and 19, respectively, in Scheme 6) already at temperatures > 50°. Photochemically 4 rearranges to a corresponding tetracyclic compound 20 via a di‐π‐methane reaction. The observed heptalene‐ and azulene‐1,2‐dicarboxylates as well as the tetracyclic compounds of type ‘anti’'‐V are formed from the primary tricyclic intermediates A via rearrangement (→heptalenedicarboxylates), retro‐Diels‐Alder reaction (→ azulenedicarboxylates), and Diels‐Alder reaction with ADM. The different reaction channels of A are dependent on the substituents. However, the main reaction channel of A is its retro‐Diels‐Alder reaction to the starting materials (azulene and ADM). The highly reversible Diels‐Alder reaction of ADM to the five‐membered ring of the azulenes is HOMO(azulene)/LUMO(ADM)‐controlled, in contrast to the at 200° irreversible ADM addition to the seven‐membered ring of the azulenes to yield the Diels‐Alder products of type E. This competing reaction must occur on grounds of orbital‐symmetry conservation under SHOMO(azulene)/LUMO(ADM) control (cf. Schemes 20–22). Several X‐ray diffraction analyses of the products were performed (cf. Chapt. 4.1).
Thermal Reactions of Guaiazulene and Its 3‐Methyl Derivative with Dimethyl Acetylenedicarboxylate
Authors: Uebelhart Peter , Hansen Hans‐Jürgen
Published: December 2004

The thermal reaction of 7‐isopropyl‐1,3,4‐trimethylazulene (3‐methylguaiazulene; 2) with excess dimethyl acetylenedicarboxylate (ADM) in decalin at 200° leads to the formation of the corresponding heptalene‐ (5a/5b and 6a/6b; cf. Scheme 3) and azulene‐1,2‐dicarboxylates (7 and 8, respectively). Together with small amounts of a corresponding tetracyclic compound (‘anti’‐13) these compounds are obtained via rearrangement (→ 5a/5b and 6a/6b), retro‐Diels‐Alder reaction (→ 7 and 8), and Diels‐Alder reaction with ADM (→ ‘anti’‐13) from the two primary tricyclic intermediates (14 and 15; cf. Scheme 5) which are formed by site‐selective addition of ADM to the five‐membered ring of 2. In a competing Diels‐Alder reaction, ADM is also added to the seven‐membered ring of 2, leading to the formation of the tricyclic compounds 9 and 10 and of the Diels‐Alder adducts ‘anti’‐11 and ‘anti’‐12, respectively of 9 and of a third tricyclic intermediate 16 which is at 200° in thermal equilibrium with 9 and 10 (cf. Scheme 6). The heptalenedicarboxylates 5a and 5b as well as 6a and 6b are interconverting slowly already at ambient temperature (Scheme 4). The thermal reaction of guaiazulene (1) with excess ADM in decalin at 190° leads alongside with the known heptalene‐ (3a) and azulene‐1,2‐dicarboxylates (4; cf. Schemes 2 and 7) to the formation of six tetracyclic compounds ‘anti’‐17 to ‘anti’‐21 as well as ‘syn’‐19 and small amounts of a 4:1 mixture of the tricyclic tetracarboxylates 22 and 23. The structure of the tetracyclic compounds can be traced back by a retro‐Diels‐Alder reaction to the corresponding structures of tricyclic compounds (24‐‐29; cf. Scheme 8) which are thermally interconverting by [1,5]‐C shifts at 190°. The tricyclic tetracarboxylates 22 and 23, which are slowly equilibrating already at ambient temperature, are formed by thermal addition of ADM to the seven‐membered ring of dimethyl 5‐isopropyl‐3,8‐dimethylazulene‐1,2‐dicarboxylate (7; cf. Scheme 10). Azulene 7 which is electronically deactivated by the two MeOCO groups at C(1) and C(2) shows no more thermal reactivity in the presence of ADM at the five‐membered ring (cf. Scheme 11). The tricyclic tetracarboxylates 22 and 23 react with excess ADM at 200° in a slow Diels‐Alder reaction to form the tetracyclic hexacarboxylates 32, ‘anti’‐33, and ‘anti’‐34 (cf. Schemes 10–12 as well as Scheme 13). A structural correlation of the tri‐ and tetracyclic compounds is only feasible if thermal equilibration via [1,5]‐C shifts between all six possible tricyclic tetracarboxylates (22, 23, and 35–38; cf. Scheme 13) is assumed. The tetracyclic hexacarboxylates 32, ‘anti’‐33, and ‘anti’‐34 seem to arise from the most strained tricyclic intermediates (36–38) by the Diels‐Alder reaction with ADM.
Non‐destructive Cleavage of N‐Acylsultams Under Neutral Conditions: Preparation of Enantiomerically, Pure Fmoc‐Protected α‐Amino Acids
Authors: Oppolzer Wolfgang , Lienard Phillippe
Published: December 2004

Heating diastereoisomerically pure N‐acylsultams 3 or 4 with allyl alcohol/Ti(OR)4 efficiently yields sultams 1 or 2 and allyl esters 5. Esters 5 are hydrolyzed under nonbasic conditions in the presence of Wilkinson's catalyst to give enantiomerically and diastereoisomerically pure carboxylic acids 7. A series of [(fluoren‐9‐yl)methoxy]‐carbonyl‐(Fmoc)‐protected amino acids 14 were thus prepared from N‐[N'‐(Fmoc)amino]acylsultams 12.
Glycosylidene Carbenes. Part 10. Regioselective Glycosidation of 4,6‐O‐Benzylidene‐D‐altropyranosides
Authors: Bozó Eva , Vasella Andrea
Published: December 2004

Glycosidation by the diazirine 1, the trichloroacetimidate 4, and the bromide 5 of the altro‐diol 2, possessing an intramolecular H‐bond (HOC(3) to OC(1)) in solution, but not in the solid state, proceeds with high and complementary regioselectivity. From 2 and 1, one obtains mostly the 1,2‐linked disaccharides 10 and 11 (β‐D > α‐D), together with the 1,3‐linked isomers 12 and 13 (α‐D > β‐D; 1,2‐/1,3‐linked products ca. 9:1), the demethylated 1,3‐linked disaccharides 24–27, the trisaccharides 19–22, the lactone azines 23, and the hydroxyglucal 18, while 2 reacted with 4 or 5 to yield mostly the 1,3‐linked disaccharides (1,2‐/1,3‐linked products ca. 1:9). The disaccharides were additionally characterized as acetates (→ 14–17, 28–31). Yields and stereoselectivity depended upon the donor, stoichiometry, solvent, temperature, and concentration. Glycosidation of the 1,3‐linked disaccharides with 1 yielded the trisaccharides 19–22. Reaction of the β‐D‐altro‐diol 3 with 1 gave the 1,2‐ and 1,3‐linked disaccharides 32/33 and 34/35 in a 1:1 ratio, characterized as the acetates 36–39, while glycosidation with 5 according to Lemieux proceeded regioselectively (1,2‐/1,3‐linked products 91:9). The monotosylates 6 and 7 reacted with 1 to yield the anomeric pairs 40/41, and 42/43 of the tosylated disaccharides; the oxiranes 44 and 45 were not observed.
Interactions between Functional Groups Part IV. The responses of four diazonium groups to adjacent electron‐rich atoms in peri‐substituted naphthalene and quinoline derivatives
Authors: Wallis John D. , Easton Robert J. C. , Dunitz Jack D.
Published: December 2004

Four peri‐substituted naphthalene‐1‐diazonium cations all show short attractive interactions between an electron‐rich atom of the peri‐substituent and the α ‐N‐atom of the diazonium group. These are interpreted as models for incipient nucleophilic attack on a NN bond. The diazonium group is a better acceptor of electron density ‘through space’ than the NO2 group, which parallels their relative ‘through‐σ‐bond’ inductive effects.
Enantioselective Synthesis of 3‐ Azabicyclo[4.3.0]nonane Alkaloids
Authors: Cid Maria Magdalena , Pombo‐Villar Esteban
Published: December 2004

The stereospecific synthesis of the monoterpene alkaloids (−)‐α‐skytanthine ((−)‐2), (−)‐N ‐demethyle‐δ‐sky‐tanthine((−)‐7), and (+)‐epidihydrotecomanine (+)‐4 was achieved from a common intermediate 22, which in turn was obtained from (1R,4S,1′S)‐2‐(1′‐phenylethyl)‐2‐azabicyclo[2.2.1]hept‐5‐ene (10),via a ketene aza‐Claisen rearrangement. The piperidine derivative (+)‐31, formally the aza‐analogue of (+)‐isoiridomyrmecin, was also obtained from the same intermediate 22.
Umsetzung von 1,3‐Thiazol‐5(4H)‐thionen mit Diazomethan
Authors: Kägi Martin , Linden Anthony , Heimgartner Heinz , Mlostoń Grzegorz
Published: December 2004

Reaction of 1,3‐Thaiazole‐5(4H)‐thiones and Diazometane

Reaction of 4,4‐dimethyl‐1,3‐thiazol‐5(4H)‐thiones 1 with diazomethane in Et2O at −78° or 0° leads to a mixture of the corresponding 1,4‐dithiane 10,1,3‐dithiole 11, thiirane 12, 4,5‐dihydro‐5methylidene‐1,3‐thiazole 13, and 1,3‐thiazol‐5(4H)‐one 14 (Scheme 3). The structures of 10a, 11a, and 11bhave been established by X‐ray crystallography. The formation of the products can be explained via an intermediate thiocaronyl ylide of type E (Scheme 4), generated by the 1.3‐dipolar cycloaddition of diazomethane with the exocyclic CS bond of 1 and elimination of N2. Head‐to‐head dimerization of E yields 10, 1, 3‐dipolar cycloaddition of E and 1 gives the ‘Schönberg product’ 11, and cyclization of E leads to 12, which undergoes a desulfurization to give 13. The thiazolone 141 is formed by hydolysis of E. The similarity of the ratio of the products at −78° and at 0° shows that, in contrast to the reaction of 1 and 2‐diazopropane, the elimination of N2 in the primary cycloadduct already occurs at −78°.
Identification of The Tocopherol‐Cyclase in the Blue‐Green Algae Anabaena variabilis KÜTZING (Cyanobacteria)
Authors: Stocker Achim , Woggon Wolf‐Dietrich , Rüttimann August
Published: December 2004

Incubation of Spheroplats of Anabaena variabilis (Cyanobacteria) with 22 the 2,6‐O‐dimetyl‐ß‐cycoldextrin complex of 2,3‐dimethyl‐5‐phytylhydroquinone (11), revealed the presence of a hitherto unknown enzyme which catalyzes the cyclization of th substrate 11 to give enantiomerically pure γ‐tocopherol (3) in ⩾ 93% yield.
Chiral Acylsilanes in Organic Synthesis. Part 2. The role of the solvent, the organometallic reagent, and the nature of the substrate for the diastereoselectivity of 1,2‐additions to racemic alkoxymethyl‐substituted acylsilanes
Authors: Chapeaurouge Alexander , Bienz Stefan
Published: December 2004

The role of the solvent, the organometallic reagent, and the nature of the substrate for the diastereoselectivity of 1,2‐additions to racemic alkoxymethyl‐substituted acylsilanes was investigated with the acylsilanes 1a–d by variation of the reaction parameters. The results obtained in this study support strongly the previously proposed preferred ‘chelate‐controlled’ reaction path followed under several reaction conditions: highest stereoselectivities were obtained with the best chelating substrates reacting with the most Lewis‐acidic organometallic reagents in the least donating solvents. It is shown that almost complete stereoselectivity can be obtained using optimal reaction conditions.
Magnetic‐Field‐Dependent Electronic Relaxation of Gd3+ in Aqueous Solutions of the Complexes [Gd(H2O)8]3+, [Gd(propane‐1,3‐diamine‐N,N,N′,N′‐tetraacetate)(H2O)2]−, and [Gd(N,N′‐bis[(N‐methylcarbamoyl)methyl]‐3‐azapentane‐1,5‐diamine‐3,N,N′‐triacetate)(H2O)] of interest in magnetic‐resonance imaging
Authors: Powell D. Hugh , Merbach André E. , González Gabriel , Brücher Ernö , Micskei Károly , Ottaviani M. Francesca , Köhler Klaus , Von Zelewsky Alex , Grinberg Oleg Ya. , Lebedev Yakob S.
Published: December 2004

EPR Spectra have been measured for aqueous solutions of a series of Gd3+ complexes at variable temperature and a range of magnetic fields; S‐band (0.14 T), X‐band (0.34 T), Q‐band (1.2 T), and 2‐mm‐band (5.0 T). The major contribution to the observed line widths is magnetic‐field‐dependent and is interpreted as being due to the modulation of the zero‐field splitting produced by distortion of the complexes from perfect symmetry. The transverse and longitudinal relaxation matrices for an 8S ion with such an interaction have been calculated using Redfield theory with vector‐coupling methods, and diagonalised numerically to obtain relaxation rates and intensities for the degenerate transitions which contribute to the multiplet. The observed line width, which is inversely proportional to the magnetic field at low temperatures, is best described by the intensity‐weighted mean transverse relaxation time for the four transitions with non‐zero intensity. A least‐squares fit of the data yields the square of the zero‐field splitting tensor, Δ2, and a correlation time, τv, with activation energy, Ev. The physical significance of these parameters and the extent of validity of the theoretical approach are considered. The parameters are used to predict the magnetic‐field dependence of the longitudinal and transverse electronic relaxation times, which are discussed in the context of their relevance to 1H‐NMR relaxivity.
Thiocarbonyl‐imide aus der Umsetzung von 2,2,4,4‐Tetramethyl‐3‐thioxocyclobutanon mit Aryl‐aziden
Authors: Mlostoń Grzegorz , Romański Jaroslaw , Linden Anthony , Heimgartner Heinz
Published: December 2004

Thiocarbonyl Imides from the Reaction of 2,2,4,4‐Tetramethyl‐3‐thioxocylobutanone and Aryl Azides

Reaction of 2,2,4,4‐tetramethyl‐3‐thioxocylobutanone (6) and 4‐methoxyphenyl, phenyl, and 4‐nitrophenyl azide (7a–c, respectively), at 80°, leads to the 11‐aryl‐5,10‐dithia‐11‐azadispiro[3.1.3.2]undecane‐2,8‐diones 8a–c (Scheme 3), respectively, in 67–83% yield. The structure of 8b has been established by X‐ray crystallography. The formation of the products may be explained via an intermediate thiocarbonyl imide of type D (Scheme 4), generated by the 1,3‐dipolar cycloaddition of the aryl azide with the CS bond of 6 and elimination of N2.
The Crystal Structure of C70 · 6(S8) at 100 K
Authors: Bürgi Hans Beat , Venugopalan Paloth , Schwarzenbach Dieter , Diederich François , Thilgen Carlo
Published: December 2004

The crystal structure of C70 · 6(S8) at 100 K shows C70 to be ordered and the S8 molecules to be partially disordered. The symmetry of C70 is D5h to within experimental accuracy.
Stereoselectivity of the Radical Reductive Alkylation of Enamines: Importance of the Allylic 1,3‐Strain Model
Authors: Schubert Serge , Renaud Philippe , Carrupt Pierre‐Alain , Schenk Kurt
Published: December 2004

Radical addition to enamines using Bu3SnH as reducing agent are reported (Schemes 2 and 4). The diastereoselectivity of these reactions was examined in different systems (Tables 1 and 2). Enamines derived from cyclic ketones such as cyclohexanone were alkylated with high diastereoselectivity with preferential formation of the cis‐disubstituted cycloalkanes. In acyclic systems such as enamines derived from propiophenone and diethyl ketone, moderate to high stereoselectivities were observed in the H‐abstraction step. A model based principally on minimization of allylic 1,3‐strain (A1,3 strain) was deduced from the experimental results and semi‐empirical (AM1) calculations.
Transition Metal‐Diene Complexes in Organic Synthesis. Part 15. Iron‐mediated total synthesis of carbazomycin A and B
Authors: Knölker Hans‐Joachim , Bauermeister Michael
Published: December 2004

We developed a very efficient methodology for the synthesis of the antibiotics carbazomycin A (1) and B (2) by oxidative coupling of cyclohexa‐1,3‐diene and the corresponding arylamine 10 (Scheme 5 and Schemes 7 and 9, resp.). The overall process is achieved by a consecutive Fe‐induced formation of the CC and the CN bond. The major benefit of our Fe‐mediated carbazole synthesis is that the coupling process is possible with fully functionalized arylamines 10. Therefore, highly convergent syntheses of carbazole alkaloids are feasible, and linear multistep sequences as required by using classical procedures are avoided. The total synthesis of 1 and 2 emphasizes this characteristic feature of the Fe‐mediated construction of the carbazole framework.
Novel Access to Furan‐3‐thiols and Derivatives, Impact Meat‐Flavor Compounds
Authors: Huber Ulrich A. , Bergamin Desirée
Published: December 2004

A versatile process for the preparation of a number of 3‐thio‐substituted furans 1–4 is described. These products have very low odor thresholds and are thus potent flavor compounds. Fur‐3‐yl thiocyanates 10a, b as well as other S‐containing analogues (2b, 7a, b, and 8) were prepared by a Michael‐type addition of thiocyanic acid, thioacetic acid, alakanethiols, and sodium thiosulfate to alkynones 6 or 15, followed by cyclization (Schemes 3 and 4). The thiocyanates 10a, b were converted to mixed disulfides 3, symmetric disulfides 4, thioethers 2, and thiols 1, using ‘hard’ or ‘soft’ nucleophiles or reducing agents, respectively (Scheme 6).
Catalytic Cyclophanes. Part IX. A Thiazolio‐cyclophane as Model for Pyruvate Oxidase and One‐Pot Synthesis of Aromatic Esters by Electrochemical Oxidation of Aldehydes Mediated by Bis(coenzyme) Catalysis
Authors: Tam‐Chang Suk‐Wah , Jimenez Leslie , Diederich François
Published: December 2004

Macrocycle 3 with a hydrophobic cavity and an appended thiazolium ring is prepared following a novel synthetic sequence to monofunctionalized cyclophanes. Although the thiazolium ring of 3 prefers to be located in the cyclophane cavity, it could be displaced with low energetic costs by benzene and naphthalene guests which form stable 1:1 inclusion complexes with 3 in protic solvents. Initial rate studies show that 3 is a pyruvate‐oxidase mimic and catalyzes the oxidation of aromatic aldehydes to carboxylic acids in aqueous solution. Cyclophane 3 also catalyzes the conversion of aromatic aldehydes to the corresponding esters in alcoholic solvents. The supramolecular catalyst 3 exhibits enzyme‐like saturation kinetics, large turnover numbers, as well as high reaction and substrate selectivity, and it is far superior to the non‐macrocyclic catalysts 4 and 5 which lack a substrate binding site. Following cyclic voltammetric investigations of the redox behavior and stability of thiazolium ions, a new one‐pot electrochemical synthesis of aromatic esters is developed: Aromatic esters are prepared efficiently by indirect electrochemical oxidation of the corresponding aldehydes in alcoholic solvents, mediated by two coenzymes, the thiazolium ions 3 or 5 and flavin 21. At the extraordinarily low working electrode potential of −300 mV (vs. Ag/AgCl), high yields of the esters are obtained with high current efficiencies and high turnovers of the catalysts which are stable under the reaction conditions. The origin of the substrate and reaction selectivity, which is particularly pronounced in the supramolecular reactions catalyzed by 3, is analyzed.
Synthesis, Structure, and Antimalarial Activity of Tricyclic 1,2,4‐Trioxanes Related to Artemisinin
Authors: Jefford Charles W. , Velarde Javier A. , Bernardinelli Gérald , Bray Dorothy H. , Warhurst David C. , Milhous Wilbur K.
Published: December 2004

Two sets of tricyclic 1,2,4‐trioxanes containing the ABC (10, 11) and ACD ring portions (21, 22, 32, 33, 37, and 38) of artemisinin (1) were synthesized by successive photo‐oxygenation of appropriate enol‐ether precursors to 1,2‐dioxanes and inter‐ and intramolecular reaction with a carbonyl compound or oxo‐substituted side‐chain. The structures of 10, 21, and 22 were determined by X‐ray analysis. The anti‐malarial activity of all trioxanes, except 37 and 38, was evaluated in vitro against chloroquine‐sensitive and chloroquine‐resistant Plasmodium falciparum parasites. Trioxanes 11 and 21 were as active as artemisinin (1). It was found that neither the lactone function nor rings B and D of 1 were essential for activity. A possible pharmacophore for artemisinin‐like activity, which embodies a spirocyclopentane group attached to C(3) of 1,2,4‐trioxane, was proposed.