bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and Configuration of Some Hydroxymilbemycin Derivatives Including 22,23‐Dihydroavermectin B1b Aglycone
Authors: Frei Bruno , Huxley Philip , Maienfisch Peter , Mereyala Hari Babu , Rist Günther , O'Sullivan Anthony C.
Published: December 2004

The synthesis of several configurationally defined hydroxymilbemycin derivatives is described. One of these allylic alcohols is the known 5‐O‐[(tert‐butyl)dimethylsilyl]‐13α‐hydroxymilbemycin D (= 5‐O‐[(tert‐butyl)‐dimethylsilyl]‐22,23‐dihydroavermectin B1b, aglycone; 15D), the synthesis of which represents LI conversion of the milbemycin to the avermectin series of natural products. The configurations at C(13), C(14), and C(15) of the new milbemycin derivatives were determined by NMR experiments and force‐field calculations.
Synthese und chemische Eigenschaften heterocyclischer Tetracyanodimethane eines heterocyclischen N,N′‐Dicyanodiimins sowie von voll substituierten monocyclischen Tetracyanodimethanen
Authors: Neidlein Richard , Bischer Alfred
Published: December 2004

Syntheses and Chemical Properties of Heterocyclic Tetracyanodimethanes of a Heterocyclic N,N′‐Dicyanodiimine and of Fully Substituted Monocyclic Tetracyanodimethanes

In the presence of different bases, 4,8‐diethoxy‐3H,7H‐benzo[1,2‐c:4,5‐c′]diisoxazole‐3,7‐dione (3) reacts with malonodinitrile or β‐oxobenzenepropanenitrile to the coloured salts 4a,b and 5, respectively, which are alkylated to the tetracyanoquinodimethane‐like heterocycles 2a,b and to the bis [benzoyl(cyano)methylidene]‐substituted heterocycle 6 (Scheme 1). Hydrogenation of 2a,b affords the fully substituted 7a,b, and with 2‐(1,3‐dithiol‐2‐ylidene)‐1,3‐dithiole, 2a gives the 1:1 charge‐transfer complex 8. Heterocyclic quinone 9 is transformed to the monocyarioimino derivative 10, and 3 reacts with cyanamide and NaH to the N,N′‐dicyanodiimine salt 12.
The Radical Anions of [2.2]Metaparacyclophane‐1,9‐diene and Some Derivatives: An ESR and ENDOR Study
Authors: Bruhin Jürg , Buser Urs , Gerson Fabian , Wellauer Thomas
Published: December 2004

The radical anion of [2.2]metaparacyclophane‐1,9‐diene (1) has been fully characterized by its hyperfine data with the use of ESR, ENDOR, and TRIPLE‐resonance spectroscopy. Assignments of all proton‐coupling constants are based on comparison with the spectra of the radical anions of the 8‐deuterio‐, 1,2,9,10‐tetradeuterio‐, and 1,10,12,13,15,16‐hexadeuterio derivative. The spin distribution in 1\documentclass{article}\pagestyle{empty}\begin{document}$ 1^{\scriptstyle {{\relbar}\kern-4pt {.} }} $\end{document} drastically differs from that in the radical anion of [2.2]metaparacyclophane (4), and it is not readily interpreted by semi‐empirical MO‐methods. The radical anions of 8‐fluoro‐ (2) and 8‐cyano[2.2]metaparacyclophane‐1,9‐diene (3) have also been investigated. Substitution of 1 by an F‐atom in the ‘exposed’ 8‐position, to yield 2, has only a minor effect on the π‐spin distribution in the radical anion, as evidenced by the similar proton‐hyperfine data for 1\documentclass{article}\pagestyle{empty}\begin{document}$ 1^{\scriptstyle {{\relbar}\kern-4pt {.} }} $\end{document} and 2\documentclass{article}\pagestyle{empty}\begin{document}$ 1^{\scriptstyle {{\relbar}\kern-4pt {.} }} $\end{document}. The 19F‐coupling constant for 2\documentclass{article}\pagestyle{empty}\begin{document}$ 1^{\scriptstyle {{\relbar}\kern-4pt {.} }} $\end{document} is much smaller than expected, thus indicating a pronounced ‘ortho‐effect’ in the pertinent position. The ESR and ENDOR spectra of 3\documentclass{article}\pagestyle{empty}\begin{document}$ 1^{\scriptstyle {{\relbar}\kern-4pt {.} }} $\end{document} in 1,2‐dimethoxyethane (counterion K+) reveal an equilibrium between a tightly and a loosely ion‐paired radical anion. Whereas the former is present exclusively in 2‐methyltetrahydrofuran (K+), the latter prevails in N,N‐dimethylformamide (Et4N+) and in mixtures of 1,2‐dimethoxyethane with N,N′,N,N″,N,′N″‐hexamethylphosphoric triamide (K+). The high temperatures required for the conformational flipping of the meta‐bridged benzene ring in 1\documentclass{article}\pagestyle{empty}\begin{document}$ 1^{\scriptstyle {{\relbar}\kern-4pt {.} }} $\end{document}, 2\documentclass{article}\pagestyle{empty}\begin{document}$ 1^{\scriptstyle {{\relbar}\kern-4pt {.} }} $\end{document}, and 3\documentclass{article}\pagestyle{empty}\begin{document}$ 1^{\scriptstyle {{\relbar}\kern-4pt {.} }} $\end{document} to be fast on the hyperfine time‐scale are well above the range appropriate for the studies of these radical anions.
Photo‐Cleavable Cryptands: Synthesis and Structure
Authors: Warmutha Ralf , Grell Ernst , Lehn Jean‐Marie , Bats Jan W. , Quinkert Gerhard
Published: December 2004

The four photo‐cleavable ligands 1–4 of the macrobicyclic‐cryptand type have been synthesized by introducing a photo‐sensitive 2‐nitrobenzyl‐ or 4,5‐dimethoxy‐2‐nitrobenzyl‐ether bond into one of the bridges. These compounds are expected to retain the selective binding features of the parent cryptands and to allow the photolytically induced release of alkali ions in aqueous solution. The crystal structures of the ligand 5‐(2‐nitro‐phenyl)‐4,7,13,16,21,24‐hexaoxa‐1,10‐diazabicyclo[8.8.8]hexacosane (3) and of its KSCN complex 13 have been determined. They are analogous to those of the corresponding parent species, confirming the macrobicyclic geometry and the cryptate nature of the complex. Spectroscopic properties are reported.
α‐D‐Glycosyl‐Substituted α,α‐D‐Trehaloses with (1 → 4)‐Linkage: Syntheses and NMR Investigations
Authors: Wessel Hans Peter , Englert Gerhard , Stangier Peter
Published: December 2004

Two symmetrical trehalose glycosyl ‘acceptors’ 4 and 6 were prepared and three of the unsymmetrical type, 8, 10, and 11. Glucosylation of symmetrical ‘acceptor’ 4 gave a higher yield of trisaccharide (44%) than protect ve‐group manipulation, namely via selective debenzylidenation 2 → 9 or monoacetylation 2 → 5 which proceeded in moderate yields (33–34%). A comparison of catalysts in the cis‐glucosylation of trehalose ‘acceptor’ 10 with tetra‐O‐benzyl‐β‐D‐glucopyranosyl fluoride 13 profiled triflic anhydride ((Tf)2O) as a new reactive promoter yielding 92% of trisaccharide 14, deblocking gave the target saccharide α‐D‐glucopyranosyI‐(1 → 4)‐α,α‐D‐trehalose. 1H‐NMR spectra of most compounds were analyzed extensively. The use of the ID TOCSY technique is advocated for its time efficiency, if needed supplemented by ROESY experiments.
Diels‐Alder Reactions of (1H‐Indol‐3‐yl)‐enacetamides and ‐endiacetamides: A Selective Access to Acetylamino‐Functionalized [b]Annelated Indoles and Carbazoles
Authors: Pindur Ulf , Otto Christian , Molinier Michel , Massa Werner
Published: December 2004

Diels‐Alder reactions of the (1H‐indol‐3‐yl)‐enacetamides and ‐endiacetamides 1a–d with some carbodieno‐philes and 4‐phenyl‐3H‐1,2,4‐triazole‐3,5(4H)‐dione give rise to the novel amino‐functionalized carbazole; 4–6 and 8 (Scheme 3). Ethenetetracarbonitrile reacts with 1b to furnish the Michael‐type adduct 7 (Scheme 3). Structural aspects of the starting materials 1, which exhibit above all 3‐vinyl‐1H‐indole reactivity, are discussed with regard to the prediction of a Diels‐Alder process.
Physovenines: Efficient Synthesis of (−)‐ and (+)‐Physovenine and Synthesis of Carbarnate Analogues of (−)‐Physovenine. Anticholinesterase Activity and Analgesic Properties of Optically Active Physovenines
Authors: Yu Qian‐sheng , Liu Chi , Brzostowska Margareth , Chrisey Linda , Brossi Arnold , Greig Nigel H. , Atack John R. , Soncrant Timothy T. , Rapoport Stanley I. , Radunz Hans‐Eckart
Published: December 2004

Column chromatography of easy available (±)‐physovenine (2) on cellulose triacetate afforded (−)‐ and (+)‐physovenine (2a and 2b, resp.). Alkaloids 2a, b required for pharmacological testing were prepared from eserolincs (3a, b) by an improved procedure. Natural (−)‐physovenine (2a) was equally potent in inhibiting AChE and BChE in vitro as natural physostigmine (1a), and twice as potent as the unnatural antipode 2b against AChE and 14 times as potent against BChE. Several carbamate analogs of 2a were at least as potent as the former compound in these assays. None of the compounds tested did bind to different opiate receptor or serotonine receptor preparations. Most of the compounds tested had considerable analgesic activity in the Writhing test.
Asymmetric Synthesis of Diazepino‐β‐lactams by [2 + 2] Cycloaddition of an ‘Evans‐Sjogven’ Ketene with 1H‐1,2‐Diazepines
Authors: Muller Marc , Bur Daniel , Tschamber Théophile , Streith Jacques
Published: December 2004

The ketene derivative of the chiral oxazolidinone 1 underwent non‐concerted stereo specific [2 + 2] cycloadditions with the (Z)‐imine moiety of diazepines 2, leading thereby with good diastereoselection to the trans‐β‐lactam adducts 3 (major) and 4 (minor). The absolute configuration of the major cycloadduct 3a was determined by an X‐ray analysis. Its formation is discussed in terms of minimisation of steric interaction in the two transition states which give sequencially the zwitterionic intermediates and the final cycloadducts.
Conformational Analysis of Marine Polyhalogenated β‐Chamigrenes Through Temperature‐Dependent NMR Spectra
Authors: Guella Graziano , Chiasera Giuseppe , Mancini Ines , Pietra Francesco
Published: December 2004

Temperature‐dependent 1H‐ and 13C‐NMR spectra reveal that polyhalogenated marine β‐chamigrenes or synthetic derivatives thereof which are trans‐diequatorially, substituted at C(8) and C(9), such as rogiolol ((−)‐2), obtusol ((+)‐3), and their acetates (+)‐1 and (−)‐4, undergo slow ring‐A chair‐chair inversion. Conformational equilibria and kinetics are investigated with the aid of synthetic model compounds and molecular‐mechanics calculations. Thus, steric repulsions between Brax–C(2) and Heq–C(7) are seen to disfavour thermodynamically conformers 1b, 2b, 3b, and 4b, which can only be detected through cross‐saturation transfer, while additional steric repulsions between Meax–C(1) and OHax–C(3) make conformer 8b of obtusol epimer so scarcely populated that it can not be detected. In agreement, with (+)‐9 and (+)‐10, which have a trigonal C(2), two conformers can be directly observed by NMR. The kinetic barriers, which are seen to arise mainly from steric repulsions between Hax–C(14) and the axial H or halogen atoms at C(8) and C(10), are calculated and discussed with respect to well documented exocycliemethylidene‐substituted cyclohexane(ene) systems. This helps to rationalize why in rogiolol acetate ((+)‐1) ring B is unusually inert towards Zn/Et2O/AcOH which causes bromohydrine‐group elimination from ring A.
Synthèse des (−)‐(6R)‐et(+)‐(6S)‐tétrahydro‐6‐[(Z)‐pent‐2‐ényl]‐2H‐pyran‐2‐one, lactones de Jasminum grandiflorum L. et de Polianthes tuberosa L.
Authors: Blaser Florian , Deschenaux Pierre‐François , Kallimopoulos Thomas , Jacot‐Guillarmod André
Published: December 2004

Synthesis of (−)‐(6R)‐ and (+)‐(6S)‐Tetrahydro‐6‐[(Z)‐pent‐2‐enyl]‐2H‐Pyran‐2‐one, lactones from Jasminum grandiflorum L. and from Polianthes tuberosa L.

(−)‐(2S)‐Ethyl 2‐hydroxyhexanedioate ((2S)‐2) was obtained by kinetic resolution of racemic ethyl 2‐hydroxy‐hexanedioate with baker's yeast. The key intermediates (+)‐(5R)‐ and (−)‐(5S)‐ethyl 5,6‐epoxyhexanoate ((5R)‐ and (5S)‐6, resp.) are proved to be useful synthons for the total synthesis of chiral 6‐alkyl‐δ‐lactones, as exemplified by the preparation of both enantiomers of jasmine lactone ((6R)‐ and (6S)‐10, resp.).
Novel Antifungal Tetracyclic Compounds from Bauhinia rufescens LAM.
Authors: Maillard Marc P. , Recio‐Iglesias Maria‐Carmen , Saadou Mahamane , Stoeckli‐Evans Helen , Hostettmann Kurt
Published: December 2004

As the root bark CH2Cl2 extract of Bauhinia rufescens showed antifungal activity in a bioassay with the plant pathogenic fungus Cladosporium cucumerinum, a phytochemical investigation was undertaken on material collected in Niger. Activity‐guided fractionation of this extract, using different preparative chromatographic methods, allowed the isolation of the four new antifungal tetracyclic compounds 1–4. Their structures were established by 1H‐ and 13C‐NMR data, and single‐crystal X‐ray analyses were used to confirm the structures of 1 and 3. The isolated compounds seem to be biogenetically related to a stilbene.
Nucleotides. Part XXXV. Synthesis of 3′‐deoxyadenylyl‐(2′–5′)‐3′‐deoxyadenyIyl‐(2′–ω)‐9‐(ω‐hydroxyalkyl)adenines
Authors: Mikhailov Sergey N. , Charubala Ramamurthy , Pfleiderer Wolfgang
Published: December 2004

Via the phosphotriester approach, new structural analogs of (2′–5′)oligoadenyiates, namely 3′‐deoxyadenylyl‐(2′–5′)‐3′‐dcoxyadenylyl‐(2′–ω)‐9‐(ω‐hydroxyalkyl)adenines 18–21, have been synthesized (see Scheme) which should preserve biological activity and show higher stability towards phosphodiesterases. The newly synthesized oligonucleotides 18–21 have been characterized by 1H‐NMR spectra, TLC, and HPLC analysis.
Nucleotides. Part XXXVI. Syntheses and biological characterization of phosphorothioate analogues of (3′–5′)adenylate trimer
Authors: Chambala Ramamurthy , Sobol Robert W. , Kon Ning , Suhadolnik Robert J. , Pfleiderer Wolfgang
Published: December 2004

The four protected diastereoisomcrs 7a/7b and 8a/8b P‐thioadenylyl‐(3′–5′)‐P‐thioadenylyI‐(3′–5′)‐adenosine were synthesized, separated, and deblocked to the free oligonucleotides (Scheme). Biochemical characterization of these (3′–5′)phosphorothioate analogues of adenyiate trimer indicate that these compounds, and the corresponding 5′‐monophosphates, neither bind to nor activate RNase L, and are considered to be valuable control compounds in screening experiments.
Dipeptide Derivatives with a Phosphonate Instead of Carboxylate Terminus by C‐Alkylation of Protected (Decarboxy‐dipeptidyl)phosphonates
Authors: Gerber Christian , Seebach Dieter
Published: December 2004

Z‐Protected diphenyl (decarboxy‐dipeptidyl)phosphonates 5a‐c with a (decarboxysarcosinyl)phosphonate moiety are prepared from Z‐L‐alanine (1a). Z‐L‐valine (1b), and Z‐L‐phenylalanine (1c) by the following series of steps: coupling with methyl sarcosinate (→2a–c), saponification (→3a–c), Hofer‐Moest oxidative decarboxyiation by electrolysis in MeOH (→4a–c), and Arbuzov reaction with P(OPh)3/TiCl4 (Scheme 3). Double deprotonation and alkylation lead to non‐stereoselective incorporation of side chains next to the phosphonate group (products of type 6–8, nine examples, see Scheme 4). In the cases of 6a–c and 8c, the diastereoisomers could be separated and the configuration of the newly formed stereogenic center deduced. We assign the L,D‐configuration to the diastereoisomers for which the 31P‐NMR signal appears at higher field.
The chemistry of coumarin derivatives. Part 3. Synthesis of 3‐alkyl‐4‐hydroxycoumarins by reductive fragmentation of 3,3′‐alkyiidene‐4,4′‐dihydroxybis[coumarins]
Authors: Appendino Giovanni , Cravotto Giancarlo , Tagliapietra Silvia , Ferraro Stefano , Nano Gian Mario , Palmisano Giovanni
Published: December 2004

Treatment of 3,3′‐alkylidene‐4,4′‐dihydroxybis[coumarins] 1 with NaBH3CN in refluxing MeOH affords 3‐alkyl‐4‐hydroxycoumarins 2 and 4‐hydroxycoumarin (3; Scheme 1). The reaction might take place via hydride trapping of alkylidenechromandiones C formed from 1 in a retro‐Michael reaction. Such a retro‐Michael reaction of 1 might be biologically relevant. The presence of C during the reductive fragmentation 1 → 2 is suggested by Diels‐Alder and nucleophilic trapping of the alkylidenechromandiones C as well as from cross‐over experiments with coumarins other than 3 (see Scheme 2). The reductive fragmentation of 1 allows the chemo‐ and regioselective synthesis of a variety of 3‐alkyl‐4‐hydroxycoumarins 2 (see Table).
The Reaction of 1,2:3,4‐Diepoxy‐2,3‐dimethylbutane with Nucleophiles
Authors: Farkas Frédéric , Wellauer Thomas , Esser Thomas , Séquin Urs
Published: December 2004

To find out whether the 1,4‐addition to 1,2:3,4‐diepoxides, which so far has been observed only once, is of a more general character, we investigated the reaction of a variety of O‐, C‐, N‐, and S‐nucleophiles with the model compound 1,2:3,4‐diepoxy‐2,3‐dimethylbutane (Scheme 4). In several cases, 1,4‐addition products could, indeed, be observed besides the expected 1,2‐adducts (Table).
Kinetic Study on Stability of Schiff Base of Pyridoxal 5′‐Phosphate and Leucine in Water Media with Cationic Surfactants
Authors: Vázquez Miguel A. , Muñoz Francisco , Donoso Josefa , García‐Blanco Francisco
Published: December 2004

We studied the stability of the Schiff bases formed between pyridoxal 5′‐phosphate (PLP) and leucine in the presence of (hexadecyl)trimethylammonium bromide (CTAB) over a wide pH range by determining the kinetic constants of formation and hydrolysis of these compounds. The results show that the stability of the Schiff bases is increased by the presence of CTAB as a result of increased rates of formation and decreased hydrolysis rate constants. The ionic head groups of CTAB favour the formation of the bases, while its hydrophobic rests protect the imine double bond from hydrolysis. This model system permits one to obtain partially hydrophobic media with no need for any non‐aqueous solvents.
Synthesis of Coumarins and Derivatives. Part 1. Biomimetic synthesis of esculetin and halogenated derivatives
Authors: Borges Fernanda , Pinto Madalena
Published: December 2004

Esculetin (1) and the novel compounds 5‐chloroesculetin (5) and 5‐bromoesculetin (6) were obtained from a light‐induced cyclization of trans‐caffeic acid (3) catalyzed by [FeNa(edta)] and/or H2SO4, HCI, or HBr (Scheme 1). The experimental conditions for trans‐cis‐isomerization of the cinnamic‐acid derivative 3 and subsequent non‐enzymatic cyclization were described. The photoperiod and the presence of air and iron‐chelate catalyst are shown to be important parameters that markedly affect yields. The reactions probably occur by a free‐radical mechanism involving a photo‐initiated one‐electron redox process (Scheme 2).
Ab‐initio‐Studien anN‐ Acyliminium‐Ionen
Authors: Lamatsch Bernd , Seebach Dieter , Ha Tae‐Kyu
Published: December 2004

Ab initioStudies onN‐Acyliminium Ions

The geometric and electronic structure and reactivity of theN‐formylmethyleneiminium ion are calculated in different conformations byab initiomethods and compared to those ofN‐methylformamide and the methyleneiminium ion. The known preferred attack of the C(5) of 3‐acyl‐2,3‐dihydro‐1,3‐oxazoles by electrophiles is explained by the lower (calculated) energy of the corresponding acyliminium ion relative to that of the oxenium ion. The stereoselectivity of additions to these acyliminium ions can not be explained by our calculations.Ab initiocalculations of the subsystems acyliminium and oxenium ion show that the reactivity can be predicted from investigation of these much simpler systems and make us suppose that a nitro instead of an acyl group will reverse the regioselectivity of the addition to 2,3‐dihydro‐1,3‐oxazoles.
Base Hydrolysis of Pentaaminecobalt (III) Complexes: The [CoX(dien) (dapo)]n+ system. Part 3. The internal conjugate base mechanism
Authors: Comba Peter , Jackson W. Gregory , Marty Werner , Zipper Luc
Published: December 2004

Azide anation and racemization of optically pure mer‐exo(H)‐ and mer‐endo(H)‐[Co(OH)(dien)(dapo)]2+ (A and B (X = OH), resp.; dien = N‐(2‐aminoethyl)ethane‐1,2‐diamine; dapo = 1,3‐diaminopropan‐2‐ol) involve the same symmetrical pentacoordinate intermediate as the base hydrolyses of the corresponding mer‐exo(H)‐ and mer‐endo(H)‐[CoX(dien)(dapo)]2+ species A and B, respectively, where X = Cl, Br, or N3. The kinetic parameters of the anation process are fully compatible with the independently measured competition ratio. The rate data reveal that substitution of OH− is unexpectedly fast, viz. it is not consistent with the usual sequence Br− > Cl− > H2O > N > OH−. This behavior is interpreted on the basis of an internal conjugate base mechanism which involves an amino‐hydroxo/aminato‐aqua tautomerism, viz. the reaction is actually an OH− ‐catalyzed substitution of [CoH2O(dien)(dapo)]3+ where deprotonation occurs effectively at the secondary‐amine site NH of dien.
Struktur zweier trans‐Bis (N,N‐dimethylethylendiamin)kobalt(III)‐Komplexe. Simulation der sterischen Ligand‐Ligand‐Wechselwirkungen durch ein ‘Molecular‐Mechanics’‐Modell
Authors: Eminger Roman , Fallab Silvio , Zehnder Margareta , Dobler Max
Published: December 2004

The Crystal and Molecular Structures of Two trans ‐Bis(N,N‐dimethylethylenediamine)cobalt(III) Complexes. Estimate of Steric Ligand‐Ligand Interactions by a Molecular‐Mechanics Model

Two trans‐bis (N,N‐dimethylethylenediamine)cobalt(III)m complexes with different axial ligands (SNC−, NO) have been synthesized starting from the corresponding CoII‐amine species. An X‐ray crystal‐structure analysis revealed widely differing CoN bond distances. While for the primary amino groups, as in complexes of unsubstituted bidentate amines, bond distances are close to 196 pm, those for the tertiary amino groups are stretched by ca. 10 pm. The good agreement between the molecular geometry as calculated by a molecular‐mechanics model and experimental data suggests that the differences in bond distances must be primarily due to simple steric effects.
Cycloaddition of Carbodiimides with a Heteroaromatic Substituent to Allenic Acids
Authors: Trifonov Latchezar S. , Christova Nadja I. , Dimitrov Valentin S. , Orahovats Alexander S.
Published: December 2004

Cycloaddition of the allenic acid 3 with the N ‐cyclohexyl‐N′ ‐heteroaromatic carbodiimides 2a and 2b gave the isomeric pyrido[1,2‐a]pyrimidinones 4 and 5 and thiazolo[3,2‐a]pyrimidinones 6 and 7, respectively, instead of the expected Diels‐Alder adducts analogous to 1. The compounds of the latter type, i.e. 8 and 9, were formed from 3 and carbodiimides 2c and 2d, respectively, containing an N′‐(pyrazin‐2‐yl) or N′‐(pyrimidin‐2‐yl) substituent.
The Vinylidene/Acyl Coupling at Rhenium Centers
Authors: Feracin Sibylle , Hund Hans‐Ulrich , Bosch H. William , Lippmann Elisabeth , Beck Wolfgang , Berke Heinz
Published: December 2004

The reaction of [Re(CO3)L2Cl] (L = (MeI)3P, 1a; L = (i‐PrO)3P, 1b; L = (PhO)3P, 1c; L = Me3P, 1d; L = Et3P, 1e) with t‐BuLi and phenylacetylene in THF affords bis (phosphorus donor) (dicarbonyl) {η2(C,O)‐[(E)‐4,4‐dimethyl‐3‐oxo‐1‐phenylpent‐1‐3n‐2‐yl]}rhenium (L = (MeO)3P, 2b; L = (PhO)3P, 2c; L = Me3P, 2d; L = Et3P, 2c). Compounds 2b and 2d were characterized by X‐ray structure analysis.
Synthesis and Photochemistry of 5,5‐Dimethyl‐1H‐pyrrol‐2(5H)‐one and of Some N‐Substituted Derivatives
Authors: Ihlefeld Andreas , Margaretha Paul
Published: December 2004

In two steps, 5,5‐dimethyl‐1H‐pyrrol‐2(5H)‐one (3a) was prepared from 5,5‐dimethylpyrrolidine‐2,4‐dione ( = dimethyltetramic acid; 4) in 71% overall yield (Scheme 1) and further converted to N‐substituted derivatives 3b–f via acylation, alkylation, or methoxycarbonylation of its anion (Scheme 2). The substituents on the N‐atom exert a strong influence on the photochemical reactivity ([2 + 2] photocycloaddition to 2,3‐dimethylbut‐2‐ene, photocyclodimerisation, photoreduction) of these aza‐enones 3 (Scheme 3). In general, N‐alkyl compounds react much slower and with less efficiency than either the (N‐unsubstituted) title compound 3a or its N‐acetyl and N‐(methoxycarbonyl) derivatives 3e and 3f, respectively. These compounds behave similarly to the corresponding lactone, 5,5‐dimethyl‐2(5H)‐furanone, studied previously.
1,3,5‐Trideoxy‐1,3,5‐tris(dimethylamino)‐cis‐inositol, an Efficient Ligand for Hard Trivalent Metal Ions. Determination of the stability constants of the FeIII, AlIII, and CuII complexes in aqueous solution
Authors: Kradolfer Thomas , Hegetschweiler Kaspar
Published: December 2004

The complexes [Fe(tdci)2]Cl3 and [Al(tdci)2]Cl3 (tdci = 1,3,5‐trideoxy‐1,3,5‐tris(dimethylamino)‐cis‐inositol) were prepared and characterized by mass spectrometry, NMR spectroscopy, and magnetic‐susceptibility measurements. The formation constants were determined in aqueous solution (25°, 0.1M KCl) by potentiometric titration. pK values of H3(tdci)3+: 5.89, 7.62, 9.68; FeIII complexes: log βML = 18.8, log β = 32.6; AlIII complexes: log βML = 14.3, logβ = 26.4. The protonated complex [FeH(tdci)2]4+ has also been identified. In contrast to the high stability of the FeIII and AlIII complexes, only weak interactions of tdci with CuII have been observed in aqueous solution (25°, 0.1M KNO3).
Pteridines. Part XCVII. Synthesis and properties of 6‐thioxanthopterin and 7‐thioisoxanthopterin
Authors: Mohr Detlev , Kazimierczuk Zygmunt , Pfleiderer Wolfgang
Published: December 2004

6‐Thioxanthopterin (13) was synthesized in four steps starting from 2‐amino‐4‐(penthyloxy)pteridine (3) via the 8‐oxide 4, its subsequent interconversion to the 6‐chloro (7) and 6‐thio derivative (12) and final hydrolysis of the pentyloxy group. 7‐Thioisoxanthopterin (15) was derived analogously from 2‐amino‐4‐(pentyloxy)pteridine‐7(8H)‐thione (14) by alkaline hydrolysis. The various 6‐ and 7‐thiopteridines were methylated to give the corresponding 6‐ (10, 11) and 7‐(methylthio) derivatives (16, 17). The newly synthesized compounds have been characterized by elemental analyses, their UV spectra, and the determination of the acidic and basic pKa values. The spectral relationships are discussed in detail.
Synthesis of Glycosylphosphine Oxides and Related Compounds
Authors: Łopusiński Andrej , Bernet Bruno , Linden Anthony , Vasella Andrea
Published: December 2004

The benzyl‐protected glycosyl acetates 1, 6, 11, and 15 react with MeOPPh2 under catalysis by TMSOTf to yield diastereoselectively the glycosylphosphine oxides 2, 3, 8, 12, 13, and 16, with a strong preference for the 1,2‐cis‐configurated anomers. Hydrogenolysis of the major products gave the crystalline, unprotected phosphine oxides 4, 9, 14, and 17, of which 4 was transformed in to the acetate 5, and 9 into the benzoate 10. The benzylated phosphine oxides 4, 8, 12, and 16 were reduced with Cl3SiH in the presence of a tertiary amine to form the phosphines 18, 21, 24, and 26, which were transformed into the phosphine sulfides 19, 22, 25, and 27. Moreover, 18 and 21, were characterized as the borane adducts 20, and 23. The structure of the (arabinofuranosyl)phosphine oxide 12, the corresponding sulfide 25, and of the borane complex 20 were established by X‐ray analysis. According to NMR spectroscopy, the equatorial pyranosylphosphine oxide 8, the sulfide 22, and the borane complex 23 adopt a 4C1 conformation. The axial phosphine oxide 2 is a flattened 4C1, the sulfide 19 exists as a B2,5, and the borane complex 20 is a flattened 4C1 in the solid sate and a B2,5 in solution. Thus, the conformational behavior of these α‐D‐glucopyranose derivatives reflects the steric requirement of the P‐substituents.
Regio‐and Stereoselectivity of Transition‐Metal‐Ion‐Mediated Single and Double Dehydrogenation of Tetraline
Authors: Seemeyer Katrin , Prüsse Tilman , Schwarz Helmut
Published: December 2004

Labeling experiments provide evidence that the Fe1‐ and CO1‐mediated losses of H2 and 2 H2 from tetraline are extremely specific in that both reactions follow a clear syn‐1,2‐elimination involving C(1)/C(2) and C(3)/C(4), respectively. In the course of the multi‐step reaction, the metal ions do not move from one side of the π‐surface to the other. Independent experiments confirm that the kinetic isotope effect (KIE) associated with the loss of the first H2 molecule is indeed larger than the KIE for the elimination of the second H2 molecule.
Structure of Rapamycin: An NMR and Molecular‐Dynamics Investigation
Authors: Kessler Horst , Haessner Rainer , Schüler Wolfgang
Published: December 2004

The highly active immunosuppressive antibiotic rapamycin is a specific inhibitor of a signal transduction pathway that results in exocytosis and transcription. We report the results of the homo‐ and heteronuclear NMR experiments of rapamycin in DMSO leading to a complete assignment of the 1H‐ and 13C‐NMR signals. With exception of one CH2 group, all diastereotopic assignments could be achieved using heteronuclear long‐range coupling constants. Restrained molecular‐dynamics simulation in the same solvent as the NMR experiments led to a well defined conformation of the rapamycin molecule in solution. Differences between the solution and crystal structures are discussed.
Intramolecular Addition of Nucleophilic Carbenes to Acceptor‐Substituted Alkenyl Groups: Synthesis and transformation of homobenzofurans and synthesis of a homoindole
Authors: Li Chunbao , Vasella Andrea
Published: December 2004

The intramolecular addition of unsaturated alkoxycarbenes leads in high yields and diastereoselectively to fused cyclopropanes (Scheme 1). Reaction of the halodiazirines 2, 10, 11, and 20 with the unsaturated phenolates 1, 8, and 9 yielded intermediate alkoxydiazirines, and hence the homobenzofurans 5, 12–16, 22, and 26 (Scheme 2). The intermediate alkoxydiazirine 25 was isolated at low temperature (Scheme 3). An equilibrium between the cyclopropane derivatives 12 and 27, and 14 and 28 was established at 120°. At 200°, 12 rearranged to the chromene 29, by disrotarory opening of the cyclopropane ring, followed by electrocyclization. Hydrogenation of 29 gave the (all‐cis)‐chroman 32 (Scheme 4). The homoindole 35 was obtained in good yields, presumably by an SRN1 reaction from 34 and 10 (Scheme 5).
A New Synthesis of Benzylidene Acetals
Authors: Li Chunbao , Vasella Andrea
Published: December 2004

Aryl‐halo‐diazirines react under basic conditions with 1,3‐cis‐, 1,2‐cisand 1,2‐trans‐diols to give acetals. Yields are high. Diastereoselectivities depend upon the diol and upon the reaction conditions. Thus, reaction of the 1,3‐cis‐diol 1 (Scheme 1) with 2 gave 3 as a single diastereoisomer. The 1,2‐cis‐diols 4 and 7 led to the endo‐ and exo‐acetals 5/6 (93:7) and 8/9 (ca.10:1), respectively, The 1,2‐trans‐diols 10, 16, and 19 reacted with 2 to afford 11/12 (90:10), 17/18 (1:1), and 20/21 (6:1), respectively. Reaction of the (4‐nitrophenyl)diazirine 13 with 10 at higher temperatures yielded 14/15 (6:4). The uracil moiety, the acetamido group, and the enol‐ether moiety are compatible with the reaction conditions. The diastereoselectivity is rationalized on the basis of a reaction sequence involving alkoxy‐halogen exchange, which is regioselective or not, thermolysis of the ensuing alkoxydiazirine(s), protonation of the alkoxycarbene to form an (E)‐configurated oxycarbenium ion, and attack of the neighboring oxy or hydroxy group, which is only possible for a limited range of conformers.
Enantioselektive Synthese von Allyl‐ und Propargylaminen durch nucleophile 1,2‐Addition an chirale Aldimine. Preliminary communication
Authors: Enders Dieter , Schankat Jürgen
Published: December 2004

Enantioselective Synthesis of Allyl‐ and Propargylamines via Nucleophilic 1,2‐ Addition to Chiral Aldinines

The asymmetric Synthesis of allylamines and propargylamines 5 in high enantiomeric purity (e.e. ⩽ 97%) is described. Key step is the 1,2‐addition of organocerium reagents to chiral α,β‐unsaturated aldimines 3 to produce secondary animes 4. The Chiral auxiliary (S,S)‐2 is removed in three steps, affording the title compounds 5, useful bifunctional building blocks and compounds of pharmaceutical interest.
On Intrahelical Hydrogen Bonding and Stability of β‐Helices: The behavior of some D,L‐alternating oligoleucines with an N‐methylated residue
Authors: Römer Daniel Urs , Fenude‐Schoch Emma , Lorenzi Gian Paolo , Rüegger Heinz
Published: December 2004

An N methylated residue at the n – 3 position of the chain was used to reduce the maximum number of H‐bonds realizable y some D,L‐alternating oligopeptides in β4.4‐, ↑↑5.6‐ and ↑↓5.6‐helices and thus increase for the oligopeptides, the relative stability of larger β‐helices. With D, L‐alternating oligoleucines of the series Boc‐Leun‐OMe, however, this approach did not produce the helices expected. Although ↑↓7.2‐helices with only one free NH per strand would theoretically be possible, the N‐methylated oligoleucines formed instead flawed β4.4‐helices having three free NH's in CHCl3 as well as in other solvents of low polarity. These observations confirm that the stability of β‐helices does not depend only on the number of intra‐or interstrand H‐bonds, and corroborate the idea that β‐helices with large cavities are inherently unstable.
A Simple Procedure for the Preparation of Chiral ‘Tris(hydroxymethyl)methane’ Derivatives
Authors: Seebach Dieter , Lapierre Jean‐Marc , Jaworek Wilfried , Seiler Paul
Published: December 2004

The aldol adducts 1a–13a of R,R‐2(tertbutyl)‐6‐methyl‐1,3‐dioxan‐4‐one (from 3‐hydroxybutanoic acid) to aldehydes, single diastereoisomers obtained as described previously, are acetylated or benzoylated to the corresponding esters 1b–5b and 6c–13c, respectively, which in turn are reduced with LiAlH4 to the title compounds 14–24. The enantiomerically pure triols thus available may be useful as chiral building blocks, as auxiliaries for enantioselective reactions, and as center pieces for chiral dendrimers.
Structural Effects on the RhII‐Catalyzed Rearrangement of Cyclopropenes
Authors: Müller Paul , Gränicher Christian
Published: December 2004

The thermocatalytic rearrangement of 2‐alkylcycloprop‐2‐ene‐1‐carboxylates (1) in the presence of RhII perfluorobutyrate is regio‐ and stereospecific and leads to the substituted metallocarbenes 3. The latter undergo intramolecular CH bond insertion to form cyclopentylidenes (4). In contrast, the metallocarbenes 19, derived from 2,3‐dialkylcycloprop‐2‐ene‐1‐carboxylates 6c, d, react to dienes (Z)‐20, via 1,2‐H migration. The cyclopropenedicarboxylates 10, in turn, rearrange exclusively to the more substituted metallocarbenes 26, which cyclize to furans 28, With 6e, and 12, products derived from both modes of ring‐opening are observed.
Preparation of optically active cyclohexenones: Chirons for the lipophilic moiety of flowery‐ and woody‐like odorant ketones
Authors: Chapuis Christian , Brauchli Robert , Thommen Walter
Published: December 2004

Optically active 2,5,6,6‐ and 2,4,4,5‐tetraalkylcyclohex‐2‐en‐1‐ones ((+)‐2a–d and (−)‐5a–d), important building blocks for flowery‐ and woody‐like odorants, have been prepared. Compounds (+)‐2a–d and (−)‐5a–d were obtained by ozonolysis of the corresponding cyclopentenic precursors, followed by intramolecular aldol condensation. Alternatively, enones (+)‐2a–d were reduced to the corresponding allylic alcohols ad converted to enones (‐)‐5a–d via acidic isomerization and oxidation. 13C‐NMR assignments are presented.
Heteronuclear Alkoxide Compounds Containing Copper and Alkaline Earth Metals
Authors: Bidell Woflgang , Bosch H. William , Veghini Dario , Hund Hans‐Ulrich , Döring Joachim , Berke Heinz
Published: December 2004

The tetrameric Cu(β‐diketonate) alkoxide complex [Cu(thd)(OCH2CH2OCH3)]4 (thd = 2,2,6,6‐tetramethyl‐3,5‐heptanedionate; 1a) reacts with the alkaline earth metal alkoxides [M(OCH2CH2OCH3)2] (M = Ca, 2a; M = Sr, 2b; M = Ba, 2c) to yield the heteronuclear compounds [Cu2M(thd)3(OCH2CH2OCH3)3] (M = Ca, 6a; M = Sr, 6b). These heterometallic complexes were also obtained in the reaction of 1a and the mixed Ca and Sr complexes of β‐diketonate‐alkoxide [Mx(thd)y(OCH2CH2OCH3)2x−y] (M = Ca, x = 7, y = 6, 3; M = Sr, x = 5, y = 3, 4), respectively. In comparison, 1a reacts with the analogous [Ba(thd)(OCH2CH2OCH3)] (5a) to yield a[Ba2Cu2(thd)4(OCH3)4(HOCH2CH2OCH3)2] species (8a.) The in situ prepared mixed‐ligand Ba Compounds [Ba(thd)OR)] (R = CH2CH2OCH2CH2OCH3, (5b); R = CH2CH2CH2OCH3 (5c) react with the corresponding Cu complexes [Cu(thd)(OR)]n (R = CH2CH2OCH2CH2OCH3), n = 4 (1b); R = CH2CH2OCH2CH2OCH3 (8b); R = CH2CH2CH2OCH3 (8c). However, [Cu(hfd)(OCH2CH2OCH3)]4 (hfd = 1,1,1,5,5,5,‐hexafluoroacetylacetonate; 1e) is converted in the presence of 2a–c to the simple metathesis products [M(hfd)2] (M = Ca, Sr, Ba) and [Cu(OCH2CH2OCH3)2]. Crystalline [Ba2Cu2(hfd)2(thd)2(OCH2CH2CH2OCH3)4(HOCH2CH2CH2OCH3)2] (9) was isolated from the reaction of 1a with in situ prepared [Ba((hfd)OCH2CH2CH2OCH3)] (5d) in 2‐, methoxyethanol. X‐Ray crystallographic structure determinations are reported for 6a, 6b, 8b, and 8c.
A Facile Conversion of Tertiary Amines into [2‐(dialkylamino)vinyl]triphenylphosphonium salts
Authors: Vorbrüggen Helmut , Krolikiewicz Konrad
Published: December 2004

Halogenation of Et3N, (i‐Pr)2EtN, and N‐ethylmorpholine or of enamines with dichlorotriphenylphosphorane gives in up to 75% yield the corresponding [2‐(dialkylamino)vinyl]triphenylphosphonium chlorides, which can be readily converted into the corresponding stable crystalline tetraphenylborates (Schemes 2 and 3).
A General Method for the Synthesis of 2′‐O‐Modified Ribonucleosides
Authors: Keller Thomas H. , Häner Robert
Published: December 2004

A general way for the functionalization of ribonucleosides is described. The method involves the synthesis of the methyl‐ribofuranoside derivative 6 equipped with a linker at the 2‐hydroxy group (Scheme 2). After introduction of the nucleic‐acid bases under standard conditions (Scheme 3), the resulting β‐D‐ribonucleosides 8 and 10 are further transformed to derivatives with lipophilic, intercalating, and aminoalkyl residues at the linker moiety. In this way, 2′‐modified 5‐methyluridines 12, adenosines 13, and 5‐methylcytidines 15 and 16 were prepared (Scheme 4).
Influence of Chelating Groups on the Luminescence Properties of Europium(III) and Terbium(III) chelates in the 2,2′‐bipyridine series
Authors: Mukkala Veli‐Matti , Kwiatkowski Marek , Kankare Jouko , Takalo Harri
Published: December 2004

Eight different 2,2′‐bipyridine derivatives, i.e. 2, 5, 8, 10, 12, 13, 15, and 19 (Schemes 1 and 2), were prepared to study the influence of the chelating groups on the luminescence properties of their EuIII and TbIII chelates. According to our luminescence results, 2,2′‐(methylenenitrilo)bis(acetic acid) as well as (methylenenitrilo)bis‐(methylphosphonic acid) in 6‐ and 6′‐position of 2,2′‐bipyridine is a suitable group when developing luminescent markers for bioaffinity assays based on time‐resolved luminescence measurement.
Sterically Congested Phosphite Ligands: Synthesis, crystallographic characterization, and observation of unprecedented eight‐Bond 31P,31P coupling in the 31P‐NMR spectra
Authors: Pastor Stephen D. , Shum Sai P. , Rodebaugh Ronald K. , Debellis Anthony D. , Clarke Frank H.
Published: December 2004

The synthesis and characterization of 2‐{1‐{3,5‐bis(1,1‐dimethylethyl)‐2‐{[2,4,8,10‐tetrakis(1,1‐dimethylethyl)dibenzo[d,f][1,3,2]dioxaphosphepin‐6‐yl]oxy}phenyl}ethyl}‐4,6‐bis(1,1‐dimethylethyl)phenyl diphenyl phosphite (6) is described. In the 31P‐NMR spectrum (1H‐decoupled) of 6, an unprecedented eight‐bond P,P coupling of J = 72.8 Hz is observed. In the X‐ray crystal structure of 6, an intramolecular P–P distance of 3.67 Å is found, which is within the sum of the van‐der‐Waals radii of the P‐atoms. The observed intramolecular P–P distance suggests that a through‐space coupling mechanism is operative. The solid‐state conformation of 6 is compared to the conformation obtained by semi‐empirical MO geometry optimizations (PM3 method). The calculated geometry suggests that the solid‐state structure is near a true energy minimum, but that crystal‐packing forces decrease the intramolecular P–P distance in the solid state. In the absence of crystal‐packing forces, however, the collisional and vibrational energy available in solution may lead to the population of states with a shortened intramolecular P–P distance in 6. The proximity of the P‐atoms in 6 is due to restricted conformational freedom resulting from steric congestion within the molecule. The free energy of activation (ΔG* = 10.2 and 10.8 kcal/mol for unequal populations of exchanging conformers) for ring inversion of the dibenzo[d,f][1,3,2]dioxaphosphepin ring in 6 is determined by variable‐temperature 31P‐NMR spectroscopy. Semi‐empirical MO calculation on model compounds suggest that the structure of the transition state for ring inversion has the two aryl rings and O‐atoms in a common plane, with the P‐atom lying above this plane.
Solid‐State CP/MAS 13C‐NMR Spectra of Oligolides derived from 3‐hydroxybutanoic acid
Authors: Riddell Frank G. , Seebach Dieter , Müller Hans‐Martin
Published: December 2004

The solid‐state CP/MAS 13C‐NMR spectra (cross‐polarization/magic‐angle spinning 13C‐NMR) of eight lower cyclic and one linear oligomers and several polymers of (R)‐3‐hydroxybutanoic acid (3‐HB) are reported. The polymeric samples of different origin and molecular weight give remarkably similar and well resolved spectra, indicating considerable similarity in the conformations of the molecules and homegeneity in the solid‐state environment. The crystalline cyclic oligomers 1–8 containing 3–9 units of 3‐HB give very well resolved spectra. The number of nonequivalent positions in the solid state can be identified and is in accord with structures from X‐ray diffraction where these were determined. The spectra of the oligolides become increasingly similar to those of the polymer as the ring size increases. This spectral evidence supports the view of a homogeneous and well defined conformation for the polymeric material (as proposed previously, based on other experiments).
Ein einfacher Zugang zu PQQ
Authors: Martin Pierre
Published: December 2004

An Easy Access to PQQ

A novel and short synthesis of PQQ, the cofactor of quinoproteins and maybe a vitamine, starting from the known cumarin 6 without any chromatographic purification of the intermediates is described.
The Chemistry of Coumarin Derivatives. Part 5. Unusual course of the reaction of 4‐hydroxycoumarin and aliphatic aldehydes
Authors: Appendino Giovanni , Cravotto Giancarlo , Nano Gian Mario , Palmisano Giovanni , Annunziata Rita
Published: December 2004

The reaction of 4‐hydroxycoumarin and certain aliphatic aldehydes affords 1:1 or complex 2:2 adducts besides (or in place) of the expected 2:1 bis(coumarin) adducts. Reaction with heptanal, cyclohexanecarbaldehyde, and pivalaldehyde are reported as representative. The structure of the reaction products was established by spectroscopical techniques, including X‐ray analysis, and their formation was mechanistically rationalized. Some of the 1:1 adducts are synthetically useful for the preparation of 3‐alkyl‐4‐hydroxycoumarins.
Enantioselective Copper‐Catalyzed 1,4‐Addition of Grignard Reagents to α,β‐Unsaturated Carbonyl Compounds
Authors: Spescha Maurus , Rihs Grety
Published: December 2004

The enantioselective copper‐catalyzed 1,4‐addition of Grignard reagents to α,β‐unsaturated carbonyl compounds was studied with the following CuI compounds as catalyst precursor and 1,2:5,6‐di‐O‐isopropylidene‐3‐thio‐α‐D‐glucofuranose (Hsiig) as chiral ligand: CuI, iodo[bis(dibutylsulfide)]copper(I), [Cu(siig)], [Cu(siig)(pp)] (pp =1,2‐bis)(diphenylphosphinoethene), and tetrakis[iodo(tributylphosphine)]copper(I). The addition of BuMg halides to cyclohex‐2‐en‐1‐one was tested under several reaction conditions. The chemical yields and regioselectivities for this reaction were, in all cases, larger than 90 and 98%, respectively, and independent of the experimental conditions. The enantioselectivity was strongly dependent on the reaction conditions and reached a maximum of 60%. Several other substrates were also tested in the above reaction. The X‐ray crystal structure for [Cu(siig)(pp)] was determined by X‐ray crystallography.
Assignment of 15N‐NMR resonances of vitamin B12 analogues by 2D‐[15N, 1H] long‐range correlation: Fully [15N]‐labelled Co‐β‐cyano‐5‐hydroxybenzimidazoylcobamide (factor III) and derivatives
Authors: Hollenstein† Roger , Stupperich Erhard
Published: December 2004

The 15N‐NMR spectra of vitamin B12 analogues obtained in fully 15N‐labelled form have been measured by direct and inverse (15N, 1H) correlated spectroscopy. All resonances, except those of the NH2 groups, have been assigned to individual N‐atoms. The influences on δ (N) are analyzed and discussed which are caused by changing the α‐face ligand from CN to H2O or CH3 and by switching the β‐face ligand from the base‐on to the base‐off state. An implication of the correct resonance assignment on biosynthetic pathways is demonstrated.
Structural Study of Pinacidil, a Potassium‐Channel Opener Belonging to the chemical class of N‐alkyl‐N″‐cyano‐N′‐pyridylguanidines
Authors: Pirotte Bernard , de Tullio Pascal , Masereel Bernard , Schynts Marc , Delarge Jacques , Dupont Léon
Published: December 2004

The crystal structure of the potassium‐channel opener (R,S)‐pinacidil (2) was determined by X‐ray crystallography. Its N′, N″‐disubstitued N‐cyanoguanidine fragment was found to exhibit an unusual (Z,Z)‐conformation. X‐Ray and NMR data obtained with 2 are consistent with the predominance of the 4‐aminopyridine species over an iminopyridine tautomer in the solid state and in solution. These new structural informations may help further comparative studies of 2 and other potassium‐channel openers in elucidating structure‐activity relationships.
Novel Acetogenins from the Leaves of Annona purpurea
Authors: Cepleanu Felicitas , Ohtani Kazuhiro , Hamburger Matthias , Hostettmann Kurt , Gupta Mahabir P. , Solis Pablo
Published: December 2004

The CH2Cl2 extract of the leaves Annona purpurea L. (Annonaceae) showed strong brine shrimp toxicity and pronounced activity against larvae of the yellow‐fever mosquito Aedes aegypti. Activity‐directed fractionation of the extract by a combination of column chromatography on silica gel, filtration, and high‐pressure liquid chromatography led to the isolation of acetogenins 1–6 as the main active principles. The structures of two novel acetogenins named purpureacin 1(5) and purpureacin 2(6) were elucidated by spectroscopic analysis (UV, EI‐ and DCI‐MS, EI‐MS of Me3Si derivatives,1H‐ and 13C‐NMR). The configuration of 5 and 6 was not established due to the limited sample amount. Compounds 3–6 also showed antifungal activity against Candida albicans, and 5 was slightly active against Bacillus subtilis.
EHT Model Studies on Coordination‐Sphere Effects in the Elementary steps of d0 transition‐metal‐catalyzed Ziegler‐Natta polymerization
Authors: Mohr Roland , Berke Heinz , Erker Gerhard
Published: December 2004

In a theoretical investigation on Ziegler‐Natta catalysis, the influence of the coordination number and ligand type of model compounds in relevant reaction steps were studied. Thus, by using the MEHT method, insertion reactions of ethylene into Zr–CH3 and Zr–H bonds were analyzed in systems of the type [Zr(C2H4)R4R′]−[Zr(Cp)(C2H4)R2R′], and [Zr(Cp)(C2H4)R3R′]−(R=R′=CH3, R=CH3, R′=H). It was found that all processes do not have significant kinetic barriers, whereas the reverse reactions in particular the β‐hydride elimination have relatively high ones. The influence of coordination geometry and number on these transformations was found to be insignificant. While studying related conversions starting from [Zr(L)(C2H4)R3R′], [Zr(Cp)(C2H4)RR′(L)]+, and [Zr(Cp)(C2H4)R2R′(L)] (L = π‐donor, R=R′=CH3 or R=CH3, R′=H) compounds a pronounced π‐donor effect was observed. Methyl insertions in these cases showed a higher computed activation barrier than hydride migrations. An orbital basis for this phenomenon was provided and conclusions concerning chain‐length control in Ziegler‐Natta catalysis were drawn.
Highly Diastereoselective Aldol Reaction of Bicyclo[3.2.1]oct‐6‐en‐3‐ones and 8‐Oxabicyclo[3.2.1]oct‐6‐en‐3‐ones. (E)‐Selective conversion into α‐alkylidene ketones
Authors: Stohrer Ingo , Hoffmann H. Martin R.
Published: December 2004

The bicyclic ketones 1–6 entered into diastereoselective (> 95% d.e.) aldol reactions with a variety of aldehydes (Scheme 1 and Table 1). A representative series of aldols was converted (E)‐selectively into α,β‐unsaturated ketones by (i) spontaneous base‐promoted dehydration (Scheme 1 and Table 2) and also by (ii) conversion into brosylate and base‐mediated elimination with lithium diisopropylamide/N,N,N′,N′‐tetramethylethylenediamine (LDA/TMEDA; Scheme 2). The simple α‐methylidene ketones 17a and 18a were obtained via oxidation of the phenylselenides 19 and 20, respectively (Scheme 4). The tertiary aldol 27 was synthesized best by treatment of 1,3‐diketone 26 with Me4Zr (Table 4). In this fashion, the facile retro‐aldol reaction of 27 was suppressed effectively.