bluuebunny/crossref_metadata_2025 huggingface dataset:
Eine überraschende Ringerweiterung von 3‐(Dimethylamino)‐2,2‐dimethyl‐2H‐azirin zu 4,5‐Dihydropyridin‐2(3H)‐on‐Derivaten
Authors: Hugener Martin , Heimgartner Heinz
Published: December 2004

An Unexpected Ring Enlargement of 3‐(Dimethylamino)‐2,2‐dimethyl‐2H‐azirine to 4,5‐Dihydropyridin‐2(3H)‐one Derivatives

The reaction of 3‐(dimethylamino)‐2,2‐dimethyl‐2H‐azirine (1a) and 4,4‐disubstituted 2‐(trifluoromethyl)‐1,3‐oxazol‐5(4H)‐ones 7 in MeCN at 70° afforded 5‐(dimethylamino)‐3,6‐dihydropyrazin‐2(1H)‐ones 10 (Scheme 4), whereas no reaction could be observed between 1a and 2‐allyl‐4‐phenyl‐2‐(trifluoromethyl)‐1,3‐oxazol‐5(2H)‐one (8a) or 4,4‐dibenzyl‐2‐phenyl‐1,3‐oxazol‐5(4H)‐one (9). The formation of 10 is rationalized by a mechanism via nucleophilic attack of 1a onto 7. The failure of a reaction with 9 shows that only activated 1,3‐oxazol‐5(4H)‐ones bearing electron‐withdrawing substituents do react as electrophiles with 1a. The amino‐azirine 1a and 2,4‐disubstituted 1,3‐oxazol‐5(4H)‐ones 2b–e in refluxing MeCN undergo a novel ring enlargement to 4,5‐dihydropyridin‐2(3H)‐ones 11 (Scheme 5). Several side products were observed in these reactions. Two different reaction mechanisms for the formation of 11 are proposed: either 1a undergoes a nucleophilic addition onto the open‐chain ketene tautomer of 2 (Scheme 6), or 2 reacts as CH‐acidic compound (Scheme 7).
3′,4′‐Diethynl‐2′,3′,5′‐trideoxy‐5′‐noruridine: A new self‐polymerizable 2′‐deoxyribonucleoside analogue
Authors: Amin Mahmoud Ahmed , Stoeckli‐Evans Helen , Gossauer Albert
Published: December 2004

In 10 steps, 3′,4′‐diethynyl‐2′,3′,5′‐trideoxy‐5′‐noruridine (14) was synthesized in 5% overall yield from commercial uridine, using conventional methods of nucleoside chemistry. As two functional groups capable to react with each other are present in the same molecule, the synthetic compound is able to form polymers, similar to the polynucleotides, by an acetylene coupling reaction.
Synthesis of Thiophene‐Substituted Spiropyrans and Spirooxazines, Precursors of Photochromic Polymers
Authors: Moustrou Corinne , Samat André , Guglielmetti Robert , Dubest Roger , Garnier Francis
Published: December 2004

The synthesis of spiropyrans 11 and 12 and spirooxazines 13–17 containing a thiophene moiety is described. Two different synthetic approaches were used. The spectrokinetic properties of these new compounds are reported.
Unparalleled, Enormous Metal–Carbon Bond Strength in PdCH2I+
Authors: Schwarz Joseph , Heinemann Christoph , Schröder Detlef , Schwarz Helmut , Hrušák Jan
Published: December 2004

Thermalized Pd+ cations activate methyl iodide by selective cleavage of a CH bond under formation of PdCH2I+ and an H‐atom. This finding implies that the interaction energy between the metal cation and the CH2I fragment and thus the metal–carbon bond strength exceeds 103 kcal/mol. Theory predicts that the energetically most favorable isomer of this ion exhibits the Pd+CH2I structure, which is stabilized by an unprecedented bridging interaction between the two heavy atoms Pd and I.
The Chemistry of Stable Carbenes. Part 2. Benzoin‐type condensations of formaldehyde catalyzed by stable carbenes
Authors: Henrique Teles J. , Melder Johann‐Peter , Ebel Klaus , Schneider Regina , Gehrer Eugen , Harder Wolfgang , Brode Stefan , Enders Dieter , Breuer Klaus , Raabe Gerhard
Published: December 2004

Stable carbenes derived from thiazole, 1H‐imidazole, and 4H‐1,2,4‐triazole are efficient catalysts for benzointype condensations of formaldehyde. Catalysts derived from N‐substituted thiazolium salts trimerize formaldehyde to dihydroxyacetone (II). Catalysts based on 1,4‐disubstituted 4H‐1,2,4‐triazol‐1‐ium salts give glycolaldehyde (I) as the main product and no II, whereas N,N′‐disubstituted 1H‐imidazol‐3‐ium salts yield mixtures of both products. The isolation of several intermediates in the catalytic cycle provide a better insight into the reaction mechanism.
Solvent‐shared radical ion pairs [pyrene·⊖Na⊕(C2H5)2]∞: ESR evidence for two different aggregates in solution, room temperature crystallization, and structural proof of another polymorphic modification
Authors: Näther Christian , Bock Hans , Claridge Rodney F. C.
Published: December 2004

The reduction of pyrene with sodium in aprotic diethyl ether allows to crystallize the extremely air‐sensitive radical ion pair pyrene‐sodium‐diethylether. The single‐crystal structure determination at 130 K shows that each sodium counter cation, solvated by one diethyl‐ether molecule, is η3‐ and η6‐coordinated to one of the short‐axis six‐membered rings of two pyrene radical anions. The resulting dibenzene‐sodium sandwiches form a string, in which the hydrocarbon planes are canted to each other by 62°. In the pyrene radical‐anion skeleton, no distortion due to its negative charge can be detected relative to that of the neutral molecule. From the temperature‐dependent signal multiplets of preceding ESR investigations, the solvent‐separated pyrene radical anion as well as two different contact radical‐ion pairs had been identified and their structures in solution approximated by potential‐energy estimates. Referring to the recently discovered long‐axis Na⊕ contact ion pair polymorph, crystallized at lower temperatures, the structure reported here represents the second and probably thermodynamically more stable one. Both the ESR and the structural results provide some insight into the multidimensional networks of equilibria in aprotic solution, which are activated by alkali‐metal reduction of unsaturated organic compounds.
Oligonucleotide Synthesis on Polystyrene‐Grafted Poly(tetrafluoroethylene) Support
Authors: Birch‐Hirschfeld Eckhard , Gührs Karl‐Heinz , Földes‐Papp Zeno , Seliger Hartmut
Published: December 2004

Supports consisting of a thin layer (2–10%) of polystyrene (PS) grafted onto a poly(tetrafluoroethylene) (PTFE) core are an interesting alternative to controlled pore glass (CPG) carriers in oligonucleotide synthesis. The beads are mechanically stable, do not show significant swelling, and allow effective removal of substrates by short washing steps with organic solvents. PTFE‐PS as an organic polymer has generally more hydrophobic properties than inorganic polymer supports and, therefore, is well compatible with organic solvents such as anhydrous MeCN. We found PTFE with a content of 2–3% PS graft to be a very good support for the synthesis of oligonucleotides of extended length. In comparison, PTFE with 5–10% grafted PS is especially useful for large‐scale syntheses. Functionalization procedures minimized in the extent of side reactions are described as well as examples for the use of the supports in syntheses of oligonucleotides both on large scale and of extended chain length.
Synthese von ‘Push‐Pull’‐ Eninen
Authors: Berger Daniel , Bartlome Andreas , Neuenschwander Markus
Published: December 2004

Synthesis of ‘Push‐Pull’ Enynes

‘Push‐pull’ enynes 1a–1f are easily available by Pd catalyzed coupling of stannyl‐ynamines 15 and silylynamines 16 with β‐iodo‐enones 8 (Schemes 7 and 8).
Metal Complexes with Macrocyclic Ligands. Part XLI. Nickel(II) and copper(II) complexes with mono‐N‐functionalized dithiadiazamacrocycles
Authors: Hörmann Esther , Riesen Pascale C. , Neuburger Markus , Zehnder Margareta , Kaden Thomas A.
Published: December 2004

Three N2S2 macrocycles (3, 10, 12) carrying an amino group as a pendant arm have been synthesized and their complexation properties towards Ni2+ and Cu2+ studied. The crystal structures of the Cu2+ complexes with 10‐methyl‐1,4‐dithia‐7,10‐diazacyclododecane‐7‐ethanamine (3) and 11‐methyl‐1,4‐dithia‐8,11‐diazacyclotetradecane‐8‐ethanamine (10) show that, in both cases, the Cu2+ is pentacoordinated by the four donor atoms of the macrocycle and the amino group of the side chain. In aqueous solution, however, two forms of the complexes with stoichiometries [MLH] and [ML] (M = Cu2+ or Ni2+) have been observed. In [MLH], the amino group is protonated and does not bind to the metal ion, whereas in [ML] the amino group is bound, and a pentacoordinated geometry results. The pKa values for the equilibrium [ML] + H+⇌[MLH]+ decrease in the order 12 > 10 > 3, indicating that the 2‐aminoethyl side chain binds better to the Cu2+ than the 3‐aminopropyl side chain. Cyclic voltammetry for the Cu2+/Cu+ pair shows that the 2‐aminoethyl pendant arm stabilizes the Cu2+ oxidation state, when the metal ion is in the 14‐membered ring (10), whereas it stabilizes Cu+ for the 12‐membered macrocycle (3).
Oligosaccharide Analogues of Polysaccharides. Part 6. Orthogonal protecting/activating groups in an improved binomial synthesis of ‘acetyleno‐oligosaccharides’
Authors: Cai Chengzhi , Vasella Andrea
Published: December 2004

Bromination of the monosilylated dialkynylated monomer 1a (Scheme 1), dimer 3 and tetramer 5 by N‐bromosuccinimide (NBS) in the presence of CF3COOAg gave 2, 4, and 6, respectively, in over 93%. Similar conditions led to bromodesilylation. Either silyl group of the diprotected monomer 1c was selectively removed by bromolysis. On the one hand, bromodesilylation of 1c gave 2 in yields varying between 80 and 99%. On the other hand, bromodesilylation of 7, obtained from 1c by hydrolytic removal of the tetrahydro‐2H‐pyran‐2‐yl (Thp) group, yielded 91% of 8. Mechanistic considerations suggested that the deprotective bromination should be improved by replacing the Me3Si by a Me3Ge group. Indeed, bromodegermylation of 1b was quantitative and ca. 60 times faster than bromodesilylation of 1c. The Me3Si and Me3Ge groups can be used for an orthogonal protection/activation of dialkynes. This was shown by desilylating 12 to 11 (Scheme 2), while bromination yielded 13. Both reactions proceeded in high yields; 9 was isolated as a minor by‐product of 13. The reactivity towards bromolysis decreases in the series H‐DOPS > Me3Ge ≈ H > Me3Si > Thp‐DOPS (DOPS = [dimethyl(oxy)‐p ropyl]dimethylsilyl). Orthogonal bromolysis of DOPS‐ and Me3Ge‐substituted dialkynes is slightly more selective than the one of Me3Si‐ and Me3Ge‐substituted analogues. Coupling of 7 with the bromoalkyne 2 gave the dimer 15 (76%), 14 (2%), and 16 (4%) (Scheme 3). The binomial synthesis was optimized so that each cycle, doubling the size of the precursor, requires the minimal number of transformations (Scheme 4). The orthogonally protected monomer 1b, dimer 19, and tetramer 22 were, on the one hand, hydrolyzed to the alcohols 18 (95%), 21 (91%), and 24(91%), respectively, and, on the other hand, bromodegermylated to 2 (99%), 4 (97%), and 6(93%). Cross‐coupling of 18 with 2, 21 with 4, and 24 with 6 gave the orthogonally protected dimer 19 (73%), tetramer 22 (87%), and octamer 25 (83%), respectively.
Effect of non‐planarity on the spin distribution in the radical anions containing the stilbene or the azobenzene π‐system: An ESR and ENDOR Study
Authors: Gerson Fabian , Lamprecht Axel , Scholz Markus , Troxler Heinz , Lenoir Dieter
Published: December 2004

The radical anions of 5H‐dibenzo[a,d]cycloheptene (9), 5 H‐dibenzo[c,f][1,2]diazepine (10), 5,6‐dihydrodibenzo[a,e]cyclooctene (11), 5,6‐dihydrodibenzo[c,g][1,2]diazocine (12), and (E)‐2,2,5,5‐tetramethyl‐3,4‐diphenylhex‐3‐ene (13) were characterized by ESR and ENDOR spectroscopy. Their hyperfine data were compared with those previously reported for radical anions also containing the stilbene or the azobenzene π‐system. Whereas the π‐spin distribution in the radical anions of the stilbene series is only moderately sensitive to deviations of the π‐system from planarity, the radical anions of the azobenzene series respond to steric strain by shifting the π‐spin population from the benzene rings to the azo group. This finding is impressively demonstrated by the similar hyperfine data for 9· − and 11· − which contrast with the strongly highly hindered 13· −. A. plausible interpretation is readily provided by the electron affinities of the constituent π‐moieties in stilbene and azobenzene. While those of benzene and ethene are both comparatively low, the azo group has a considerably higher electron affinity.
Model Studies Towards a Novel Fragment Coupling for the Synthesis of Mycalamides and Related Natural Products
Authors: Hoffmann Reinhard W. , Breitfelder Steffen , Schlapbach Achim
Published: December 2004

The mycalamides (3) and related natural products contain an α‐hydroxy acid 1 bound via an amide bond to an α‐alkoxy amine. The high density of functional groups in the ‘coupling region’ renders the coupling reactions delicate. Model studies showed that an alternate assembly of the molecular halves is possible using an ‘Umpolung’ of an α‐alkoxy isocyanate, e.g. 13. Thus, combination of the ester 12 with 13 led to the α‐keto amide 16. The further elaboration of 16 to the α‐hydroxy‐amide structure found in the mycalamides is reported.
Corniculoside, a New Biosidic Ester Secoiridoid from Halenia corniculata
Authors: Rodriguez Sylvain , Wolfender Jean‐Luc , Hostettmann Kurt , Odontuya Gendaramyn , Purev Ondognii
Published: December 2004

Chemical screening of the secondary metabolites from Halenia corniculata L. (CORNAZ), by LC/UV,LC/TSP‐MS (thermospray), and LC/ES‐MS (electrospray) was used for the targeted isolation of corniculoside (1), a new biosidic ester secoiridoid. The structure was established as 7‐β‐[(E)‐4′‐O‐(β‐D‐glucopyranosyl)caffeoyloxy]‐sweroside by 1D‐ and 2D‐NMR, LC/UV, LC/MS, and FAB‐MS data, in combination with chemical reactions.
Diazoaldehyde Chemistry. Part 3. Synthesis of 4‐acyl‐1H‐1,2,3‐triazole derivatives
Authors: Sezer Özkan , Dabak Kadir , Akar Ahmet , Anaç Olcay
Published: December 2004

Ten new α‐diazo‐β‐oxoaldehydes were condensed with aniline, ammonia, hydroxylamine, and semicarbazide to yield new 4‐acyl‐(1‐substituted)‐1H‐1,2,3‐triazoles in moderate‐to‐good yields. The method is simple and regiospecific. The latter feature makes this method superior to the widely used acylacetylene + azide approach.
N7‐DNA: Synthesis and Base Pairing of Oligonucleotides Containing N7‐(2‐Deoxy‐β‐D‐erythro‐pentofuranosyl)guanine (N7Gd)
Authors: Seela Frank , Leonard Peter
Published: December 2004

The synthesis of oligonucleotides containing N7‐(2‐deoxy‐β‐D‐erythro‐pentofuranosyl)guanine (N7Gd; 1) is described. Compound 1 was prepared by nucleobase‐anion glycosylation of 2‐amino‐6‐methoxypurine (5) with 2‐deoxy‐3,5‐di‐O‐(4‐toluoyl)‐α‐D‐erythro‐pentofuranosyl chloride (6) followed by detoluoylation and displacement of the MeO group (8→10→1). Upon base protection with the (dimethylamino)methylidene residue (→11) the 4,4‐dimethoxytrityl group was introduced at OHC(5′) (→12). The phosphonate 3 and the phosphoramidite 4 were prepared and used in solid‐phase oligonucleotide synthesis. The self‐complementary dodecamer d(N7GC)6 shows sigmoidal melting. The Tm of the duplex is 40°. This demonstrates that guanine residues linked via N(7) of purine to the phosphodiester backbone are able to undergo base pairing with cytosine.
Synthesis of 4‐Substituted 1H‐Benzimidazole 2′‐Deoxyribonucleosides and Utility of the 4‐Nitro Compound as Universal Base
Authors: Seela Frank , Bourgeois Werner , Rosemeyer Helmut , Wenzel Thomas
Published: December 2004

The stereoselective synthesis of 4‐substituted 1H‐benzimidazole 2′‐deoxyribonucleosides is described. Regioisomeric (N1 and N3) β‐D‐deoxyribonucleosides 2a–c and 3a–c were formed. 13C‐NMR Chemical shifts of the 1H‐benzimidazole 2′‐deoxy‐β‐D‐ribofuranosides were correlated with point charges of C‐atoms as well as with Hammett constants of the exocyclic substituents. Phosphonate and phosphoramidite building blocks of 4‐nitro‐1H‐benzimidazole 2′‐deoxyribofuranoside (2a) were prepared (see 4a, b). Oligonucleotides of the d(A20) type were synthesized in which the two central dA bases were replaced by 4‐nitro‐1H‐benzimidazole residues. They were hybridized with oligomeric dT and related oligomers having the other conventional bases opposite to the 4‐nitro‐1H‐benzimidazole moieties. Within these duplexes (12·13, 12·14, 12·15, and 12·16), the destabilization was almost independent of the mismatch which is required for a universal base. The thermodynamic data indicate that the 4‐nitro‐1H‐benzimidazole residues do not form H‐bonds with opposite bases but are stabilizing the duplex by stacking interactions and favorable entropic changes.
Studied Directed toward the Synthesis of Phomenoic Acid. Part 2. Stereocontrolled Synthesis of the C(7)‐to‐C(14) Segment
Authors: Hassan Hammed H. A. M. , Tamm Christoph
Published: December 2004

Starting from the esters (2E,4S)‐6 and (2E,4R)‐6, bromo aldehydes (S)‐9 and (R)‐9 as well as bromo alcohols (S)‐10 and (R)‐10, respectively, were prepared. Bromo alcohol (R)‐8 was converted to the diol (2E,4R)‐16. Ozonolysis of the latter led to aldehyde (R)‐17, which was transformed, by a Wittig reaction, to (2R,4E,6R)‐18, corresponding to the C(7)‐to‐C(14) segment of phomenoic acid (1). Attempts to improve the yields by applying a Julia coupling of (R)‐23, which was prepared from (2E,4R)‐7, with (R)‐24 were unsuccessful. Finally, the coupling of the iodo derivative (2E,4S)‐28 with the lithiated derivative of 1,3‐dithiane 30 by the Corey‐Seebach ‘Umpolung’ led to (3S,4E)‐32 which is a derivative of the C(7)‐to‐C(14) segment of 1, suitable for further transformations.
Synthese der p‐Cumaroylspermidine
Authors: Hu Wenqing , Hesse Manfred
Published: December 2004

The Synthesis of p‐Cumaroylspermidines

The synthesis of three mono[(E)‐3‐(4‐hydroxyphenyl)prop‐2‐enoyl]spermidines, 10, 20, and 28, three bis[(E)‐3‐(4‐hydroxyphenyl)prop‐2‐enoyl]spermidines, 6, 16, and 25, and one tris[(E)‐3‐(4‐hydroxyphenyl)prop‐2‐enoyl]‐spermidine is described.
Nucleosides. Part LX. Synthesis and Characterization of Monomeric Cordycepin‐Vitamin and Cordycepin‐Lipid Conjugates Model Substances for Biodegradable Ester and Carbonate Linkages in Conjugates and Potential Inhibitors of HIV‐1 Replication
Authors: Wasner Marita , Pfleiderer Wolfgang , Suhadolnik Robert J. , Horvath Susan E. , Kon Ning , Guan Ming‐Xu , Henderson Earl E. , Suhadolnik Robert J. , Henderson Earl E. , Adelson Martin E.
Published: December 2004

Monomeric 3′‐deoxyadenosine (cordycepin) was modified at the 2′‐O‐ (13–18) and 5′‐O‐position (25–29) by the vitamins E, D2, and A and by the two lipids 1,2‐di‐O‐palmitoylglycerol and 1,2‐di‐O‐hexadecylglycerol via succinate or carbonate linkages. The base‐labile conjugates afforded protection groups like the 2‐(4‐nitro‐phenyl)ethoxycarbonyl (npeoc) and monomethoxytrityl group (MeOTr) that are cleavable without harming the ester and carbonate bonds, respectively. Monomeric conjugates of cordycepin and vitamin E, vitamin D2, 1,2‐di‐O‐palmitoylglycerol, and 1,2‐di‐O‐hexadecylglycerol (see 13, 14, 17, 18, 25, 26, 28, and 29) inhibited HIV‐1‐induced syncytia formation 1.7 to 6.2 fold compared to 1.5‐fold for cordycepin (see Table); IC50 values for 25 and 28 were 257 and 267 m̈M, respectively. In addition, the monomeric cordycepin‐vitamin and ‐lipid conjugates inhibited HIV‐1 RT activity 28–49% which compares with a 13% inhibition of HIV‐1 RT observed for cordycepin. The minimal inhibition of HIV‐1‐induced syncytia formation and HIV‐1 RT activity did not proceed by the activation of RNase L. The monomeric conjugates tested (13, 14) increased PKR expression.
Syntheses of New Isocephems and Isodethiaoxacephems as Antimicrobial Agents
Authors: Hakimelahi Gholam H. , Hwu Jih Ru , Tsay Shwu‐Chen , Ramezani Zahra , Hwu Jih Ru
Published: December 2004

The cis‐configurated isocephem 26 as well as isodethiaoxacephems 21 and 33 were synthesized (Schemes 4 and 5). The key step involves chlorination of the corresponding carbanions of 23, 18, and 31 with CF3SO2Cl followed by internal alkylation. β‐Lactams 3, 21, 26, and 33 were found to possess biological activity against several pathogenic microorganisms in vitro. Electronic activation of the lactam moiety in isodethiaoxacephem 33 remarkably enhanced its biological activity.
Struktur des Zwischenproduktes einer (i‐PrO)2 TiMe2‐Methylierung: NMR‐Untersuchungen und Konformationsanalyse
Authors: Hollenstein Sandro , Hesse Manfred
Published: December 2004

Structure of the Intermediate of a Methylation with (i‐PrO)2TiMe2: NMR Investigations and Conformational Analysis

The intermediate of the reaction of 3‐(1‐nitro‐2‐oxocyclohexyl)propanal ((±)‐1) with (i‐PrO)2TiMe2 was shown to be a titanium salt of 6‐(hydroxynitroryl)decano‐9‐lactone. 1H‐, 13C‐, HSQC‐, 1H,1H‐TOCSY‐ and long‐range HMBC‐NMR spectra of this intermediate indicate a complexation of the carbonyl O‐atom and an O‐atom of the hydroxynitroryl group to the same Ti‐atom. The product of the reaction (t‐3‐methyl‐c‐6‐nitro‐2‐oxabicyclo[4.4.0]decan‐r‐1‐ol, (±)‐2) was reacted with several titanium reagents to give also titanium salts of the 6‐(hydroxynitroryl)decano‐9‐lactone. Monte Carlo studies and MM3* force‐field calculations of the anion of 6‐(hydroxynitroryl)decano‐9‐lactone, 3′, resulted in a conformation of the ten‐membered ring (only 9.57 kJ/mol higher in energy than the global minimum), which allows the Ti‐atom to coordinate to the O‐atom of the N(O)OH and CO group at the same time. With the suggested structure of 3′ · TiRn, we are able to explain the selectivity of the reaction.
Synthesis of Oncinotin‐11‐one, a Macrocyclic Polyamine Alkaloid from Oncinotis tenuiloba
Authors: Doll Martin K.‐H. , Guggisberg Armin , Hesse Manfred
Published: December 2004

This paper presents a short synthesis of oncinotin‐11‐one (11), a minor alkaloid of Oncinotis tenuiloba (Apocynaceae). Based on a disconnection approach, the spermidine portion of the key intermediate 6 was constructed consecutively by simple N‐alkylations starting from ethyl piperidine‐2‐carboxylate (1). Treatment of 6 with in situ lithiated 2‐[(10‐bromodecyl)oxy]tetrahydropyran resulted in the formation of the keto moiety under simultanous deprotection of the lactam N‐atom to give the amino ketone 7 in 71% yield. Cleavage of the tetrahydro‐2H‐pyran‐2‐yl(Thp) portion and Jones oxidation of the resulting alcohol 8 gave the amino acid 9 which was cyclized. Final N‐debenzylation of 10 provided the natural alkaloid 11. Only two protective groups were needed in this synthesis. The reaction of N‐alkyl‐lactams with organometallic reagents is discussed.
A New Approach to the Synthesis of Long‐Chain Polypropionates Based on the Diels‐Alder Monoadditions of 2,2′‐Ethylidenebis[3,5‐dimethylfuran]
Authors: Ancerewicz Jacek , Vogel Pierre
Published: December 2004

Acidic condensation of 2,4‐dimethylfuran with acetaldehyde provided 2,2′‐ethylidenebis[3,5‐dimethylfuran] (7) which added 1 equiv. of methyl bromopropynoate to give a major adduct 8. Regio‐ and stereoselective hydroboration of the latter 7‐oxanorbornadiene derivative followed by alcohol protection and methanolysis of its β‐bromoacrylate moiety gave (1RS,2RS,4RS,5SR,6SR,1′RS)‐methyl 4‐[1′‐(3″,5″‐dimethylfuran‐2″‐yl)ethyl]‐3,3‐dimethoxy‐6‐exo‐[(2‐methoxy)ethoxy]‐1,5‐endo‐dimethyl‐7‐oxabicyclo[2.2.1]heptane‐2‐endo‐carboxylate (24) (Schemes 2 and 3). Reduction of 24 with LiAlH4, followed by H2O and MeOH elimination gave the 3‐methyl‐idene‐7‐oxanorbornan‐2‐one derivative 26 which underwent 7‐oxa ring opening through a SN2′ type of reaction with Me2CuLi (Scheme 4). Stereoselective hydrogenation and ketone reduction provided (1RS, 2SR,3RS,4RS,5RS,6RS,1′SR)‐1‐ [1″‐(3 ″,5″‐dimethylfuran‐2″‐yl)]‐c‐3‐ethyl‐c‐5‐[(2‐methoxyethoxy)m e‐c‐ethyl‐c‐c‐5‐(2‐methoxyethoxy)methoxy]‐t‐4,t‐6‐dimethyl‐cyclohexane‐r‐1,c‐2‐diol (32), the oxidative cleavage of which with Pb(OAc)4 generated a 6‐oxo‐aldehyde 33 (Schemes 4 and 5). Chemoselective protection of 33 and chemo‐ and stereoselective reductions generated (2RS,3RS,4SR,5SR,6SR,7RS)‐7‐(3′,5″‐dimethylfuran‐2′‐yl)‐2‐ethyl‐6‐hydroxy‐4‐[(2‐methoxyethoxy)methoxy]‐3,5‐dimethyloct‐1‐yl pivaloate (36) and its 4‐hydroxy 6‐epimer 40 (12 and 13 steps, resp., from adduct 8; Scheme 5). Oxidation of the furan ring of 36 led to a (2RS,3SR,4RS,5SR,6RS,7RS)‐7‐ethyl‐3,5,8‐trihydroxy‐2,4,6‐trimethyl‐octanoic acid derivative 44, a polypropionate fragment with six contiguous stereogenic centres (Scheme 6).
2‐Alkynylcyclopent‐2‐enols from 2‐Alkynylcyclohex‐2‐enones via 1‐Alkynyl‐7‐oxabicyclo[4.1.0]heptan‐2‐ones
Authors: Sander Birgit , Andresen Sven , Reichow Stefan , Dubois Katia , Agosta William C. , Margaretha Paul
Published: December 2004

2‐Alkynylcyclohex‐2‐enones 1a–c and 2a–c react with H2O2/NaOH in MeOH to afford 1‐alkynyl‐7‐oxabicyclo[4.1.0]heptan‐2‐ones 3a–c and 4a–c, respectively. The 3‐unsubstituted bicyclic epoxy ketones 3a, 3b, and 4a, 4b react further with H2O2/NaOH, undergoing ring contraction and (formal) decarbonylation to give 2‐alkynylcy‐clopent‐2‐enols 5a, 5b, and 6a, 6b, respectively. Epoxy ketones 3 are also obtained under neutral conditions on irradiation (λ = 350 nm) of cyclohexenones 1 in air‐saturated benzene solution. Similarly, under neutral conditions oxo‐cycloalkenecarbonitriles 8 react (thermally) with H2O2 in MeCN to give the oxabicyclic carbonitriles 9.
Xylose‐DNA Containing the Four Natural Bases
Authors: Seela Frank , Heckel Maximilian , Rosemeyer Helmut
Published: December 2004

Oligonucleotides containing (2′‐deoxy‐β‐D‐xylofuranosyl)guanine have been prepared. For this purpose 2‐aminoadenosine (5) was synthesized and converted to 2′‐deoxy‐β‐D‐xyloguanosine (1). The related 2′‐deoxy‐β‐D‐xyloisoguanosine (3) and 2′‐deoxy‐β‐D‐xyloxanthosine (4) were also synthesized. Compound 1 was converted to the phosphonate and phosphoramidite building blocks 10 and 11, respectively. The oligodeoxynucleotide (5′‐3′)d(xG‐xT‐xA‐xG‐xA‐xA‐xT‐xT‐xC‐xT‐xA‐xC‐T) (18) formed a duplex with the same Tm as the parent (5′‐3′)‐(G‐T‐A‐G‐A‐A‐T‐T‐C‐T‐A‐C) (19), but with an inverted CD spectrum.
Synthesis of 2′‐Deoxy‐5‐(isothiazol‐5‐yl)uridine and Its Interaction with the HSV‐1 Thymidine Kinase
Authors: Luyten Ingrid , Winter Hans De , Busson Roger , Lescrinier Theo , Creuven Isabelle , Durant Françlois , Balzarini Jan , De Clercq Erik , Herdewijn Piet
Published: December 2004

2′‐Deoxy‐5‐(isothiazol‐5‐yl)uridine (12) was synthesized starting from 2′‐deoxy‐5‐iodouridine using a Pd‐catalysed cross‐coupling reaction with propiolaldehyde diethyl acetal followed by deprotection and ring closure using thiosulfate. 2′‐Deoxyuridine 12 has a particular place among the 5‐heteroaryl‐substituted 2′‐deoxyuridines in that it has a high affinity for herpes simplex virus type 1 (HSV‐1)‐encoded thymidine kinase (TK) without antiviral activity. Biochemical studies revealed that 12 is a substrate for viral TK. We further investigated the interaction of 12 with the HSV‐1 thymidine kinase. The conformation of 12 in solution was established by NMR spectroscopy. The most stable conformer 12A has the S‐atom of the isothiazole ring placed in the neighbourhood of the C(4)O group of the pyrimidine moiety. The compound was docked in its most stable conformation in the active site of HSV‐1 TK and subjected to energy minimization. This demonstrated that the isothiazole moiety binds in a cavity lined by the side chains of Tyr‐132, Arg‐163, Ala‐167, and Ala‐168 and that the C(3) atom of the isothiazole moiety is located in close proximity of the phenolic O‐atom of Tyr‐132 and the aliphatic part of the Arg‐163 side chain.
The Deoxygenation and Isomerization of Artemisinin and Artemether and Their Relevance to Antimalarial Action
Authors: Jefford Charles W. , Vicente Maria G. H. , Jacquier Yvan , Favarger France , Mareda Jiri , Millasson‐Schmidt Patricia , Brunner Gerhard , Burger Ulrich
Published: December 2004

The treatment of artemisinin (1) and β‐artemether (6) with Zn dissolving in AcOH for a few hours results in mono‐deoxygenation giving deoxyartemisinin (5) and deoxy‐β‐artemether (7), respectively, as the sole product. In contrast, submission of 1 to FeCl2 · 4 H2O in MeCN at room temperature for 15 min causes only isomerization, (3aS,4R,6aS,7R,10S,10aR)‐octahydro‐4,7‐dimethyl‐8‐oxo‐2H‐10H‐furo[3,2‐i] benzopyran‐10‐yl acetate (8) and (3R)‐3‐hydroxydeoxyartemisinin (9) being produced in 78 and 17% yield, respectively. The action of FeCl2 · 4 H2O in MeCN on 6 is similar. Under the same conditions, 6 gives products analogous to 8 and 9 accompanied by an epimeric mixture of 2‐[4‐methyl‐2‐oxo‐3‐(3‐oxobutyl)cyclohexyl]propanaldehyde in yields of 32, 23, and 16%, respectively. No epoxide is formed on repeating the last two experiments in the presence of cyclohexene. The deoxygenation of 1 and 6 by Zn is rationalized in terms of its oxophilic nature. The catalyzed isomerization of 1 and 6 by Fe2+ is attributed to the redox properties of the Fe2+/Fe3+ system.
C‐Glycoside Analogues of N4‐(2‐Acetamido‐2‐deoxy‐β‐D‐glucopyranosyl)‐L‐asparagine: Synthesis and conformational analysis of a cyclic C‐glycopeptide
Authors: Hoffmann Matthias , Burkhart Fred , Hessler Gerhard , Kessler Horst
Published: December 2004

The synthesis of C‐glycosidic analogues 15–22 of N4‐(2‐acetamido‐2‐deoxy‐β‐D‐glucopyranosyl)‐L‐asparagine (Asn(N4GlcNAc)) possessing a reversed amide bond as an isosteric replacement of the N‐glycosidic linkage is presented. The peptide cyclo(‐D‐Pro‐Phe‐Ala‐CGaa‐Phe‐Phe‐) (CGaa = C‐glycosylated amino acid; 24) was prepared to demonstrate that 3‐[(3‐acetamido‐2,6‐anhydro‐4,5,7‐tri‐O‐benzyl‐3‐deoxy‐β‐D‐glycero‐D‐guloheptonoyl)amino]‐2‐[(9H‐fluoren‐9‐yloxycarbonyl)amino]propanoic acid (22) can be used in solid‐phase peptide synthesis. The conformation of 24 was determined by NMR and molecular‐dynamics (MD) techniques. Evidence is provided that the CGaa side chain interacts with the peptide backbone. The different C‐glycosylated amino acids 15–21 were prepared by coupling 3‐acetamido‐2,6‐anhydro‐4,5,7‐tri‐O‐benzyl‐3‐deoxy‐β‐D‐glycero‐D‐gulo‐heptonic acid (4) with diamino‐acid derivatives 8–14 in 83–96% yield. The synthesis of 4 was performed from 2‐(acetamido‐3,4,6‐tri‐O‐benzyl‐2‐deoxy‐β‐D‐glucopyranosyl) tributylstannane (2) by treatment with BuLi and CO2 in 83% yield. Similarly, propyl isocyanat yielded the glycoheptonamide 7 in 52% from 2. Compound 2 was obtained from 2‐acetamido‐3,4,6‐tri‐O‐benzyl‐2‐deoxy‐D‐glucopyranose (1) by chlorination and addition of tributyltinlithium in 74% yield. A procedure for a multigram‐scale synthesis of 1 is given.
Duplex Stability of 7‐Deazapurine DNA: Oligonucleotides containing 7‐bromo‐ or 7‐iodo‐7‐deazaguanine
Authors: Ramzaeva Natalya , Seela Frank
Published: December 2004

The oligonucleotide building blocks, the phosphonates 1a, b and the phosphoramidites 2a, b derived from 7‐iodo‐ and 7‐bromo‐7‐deaza‐2′‐deoxyguanosines 3a, b were prepared. They were employed in solid‐phase oligonucleotide synthesis of the alternating octamers d(Br7c7G‐C)4 (8) and d(I7c7G‐C)4 (9) as well as the homo‐oligonucleotides d[(Br7c7G)5‐G] (11) and d[(I7c7G)5‐G] (12). The melting profiles and CD spectra of oligonucleotide duplexes were measured. The Tm values as well as the thermodynamic data were determined and correlated to the major‐groove modification of this DNA. The self‐complementary octamers 8 and 9 form more stable duplexes compared to the parent oligomer d(G‐C)4. The heteroduplex of d[(I7c7G)5‐G] (12) with d(C6) is slightly destabilized (ΔTm = −12°) over that of d[(c7G)5‐G] with d(C6). However, the complex of 12 with poly(C) is more stable than that of d[(c7G5‐G)] with poly(C).
The Crystal and Molecular Structure of [Co(tmen)3](C7H7SO3)3·2 H2O and [Co(tmen)3](CH3SO3)2·EtOH·1/2 H2O (tmen = 2,3‐dimethylbutane‐2,3‐diamine)
Authors: Brunner Hans , Ludi Andreas , Raselli Andrea , Bürgi Hans‐Beat
Published: December 2004

The molecular structure of the two complex ions [Co(tmen)3]3+ and [Co(tmen)3]2+ (tmen = 2,3‐dimethylbutane‐2,3‐diamine) have been determined at 100 K. They show a strong trigonal distortion of the octahedral CoN6 core. The twist angle is 26.2(2.8)° for CoII and 43.9(9)° for CoIII. Average CoN distances are 2.193(13) Å (CoII) and 1.997(2) Å (CoIII), 0.02 Å longer than for the main body of CoIII amines.
Antiplatelet α‐Methylidene‐γ‐butyrolactones: Synthesis and evaluation of quinoline, flavone, and xanthone derivatives
Authors: Wang Tai‐Chi , Chen Yeh‐Long , Tzeng Cherng‐Chyi , Liou Shorong‐Shii , Chang Ya‐Ling , Teng Che‐Ming
Published: December 2004

As a continuation of our previous studies on the synthesis and antiplatelet activity of coumarin derivatives of α‐methylidene‐γ‐butyrolactones, certain quinoline, flavone, and xanthone derivatives were synthesized and evaluated for antiplatelet activity against thrombin (Thr)‐, arachidonic acid (AA)‐, collagen (Col)‐, and platelet‐activating factor (PAF)‐induced aggregation in washed rabbit platelets. These compounds were synthesized from quinolin‐8‐ol, flavon‐7‐ol, and xanthon‐3‐ol, respectively, via alkylation and Reformatsky‐type condensation (Schemes 1–3). By the comparison with comparison with coumarin α‐methylidene‐γ‐butyrolactone 3a, flavone and xanthone derivatives, 3b and 3c, respectively, are more selective in which only AA‐ and collagen‐induced aggregation are strongly inhibited. Most of the quinoline derivatives (9a–e) exhibited broad‐spectrum antiplatelet activities.
The Radical Ions of Dipleiadiene (Dicyclohepta[de,ij]naphthalene) and Its 12b,12c‐Homo Derivative. An ESR and ENDOR study
Authors: Bachmann Rainer , Gerson Fabian , Merstetter Pascal , Vogel Emanuel
Published: December 2004

The radical anions and the radical cations of dipleiadiene (dicyclohepta[de,ij]naphthalene; 1) and its 12b, 12c‐homo derivative 2 were characterized by ESR and ENDOR spectroscopy. Their singly occupied orbitals are related to the degenerate nonbonding MOs of a 16‐membered π‐perimeter. The π‐spin distribution over the perimeter is similar in the radical cations 1.+ and 2.+, and an analogous statement holds for the radical anions 1.− and 2.−. However, deviations of the π‐system from planarity lead to a decrease in the absolute values of the negative coupling constants of the perimeter protons in 2.+ and 2.− relative to those in 1.+ and 1.−. The hyperfine data for the perimeter protons in the radical ions correlate with the changes in 13C chemical shifts on passing from the neutral compounds to the corresponding diions. It is concluded from the coupling constants of the CH2 protons in the radical ions of 2 that the cation 2.+ exists in the methano‐bridged form (A) of the neutral 2 (and, presumably, also of the dication 22+), whereas the anion 2.− adopts the bisnorcaradiene form (B) of the dianion 22−.
Transfer Mechanism of Ionic Drugs: Piroxicam as an agent facilitating proton transfer
Authors: Reymond Frédéric , Steyaert Guillaume , Pagliara Alessandra , Carrupt Pierre‐Alain , Testa Bernard , Girault Hubert
Published: December 2004

Facilitated proton transfer may be of potential significance in pharmacokinetic and pharmacodynamic processes. Here, we show that the NSAID piroxicam and its N‐and O‐methylated derivatives act as ionophores for proton transfer across the H2O/1,2‐dichloroethane interface. Investigations by cyclic voltammetry showed that the proton transfer occurs by interfacial protonation of the ionophore. The dissociation constants of the three compounds in the organic phase were calculated by Matsuda's theory. With this particular transfer mechanism, the present study exemplifies how electrochemistry at a liquid/liquid interface can be applied to calculate the fundamental thermodynamic parameters related to the pharmacokinetic behavior of ionic drugs.
Synthesis and Enzymatic Evaluation of Substrates and Inhibitors of β‐Glucuronidases
Authors: Hoos Roland , Huixin Jiang , Vasella Andrea , Weiss Patrick
Published: December 2004

The phosphono and the tetrazolyl analogues 4 and 5 of 4‐methylumbelliferyl β‐D‐glucuronide (=(4‐methyl‐2‐oxo‐2H‐1‐benzopyran‐7‐yl β‐D‐glucopyranosid)uronic acid; 6) were synthesized and evaluated as substrates of β‐glucuronidases. Similarly, the phenylcarbamate 7 and its phosphono analogue 8 were prepared and evaluated as inhibitors. To examine the diastereoselectivity of the phosphorylation, we also synthesized the protected L‐ido‐D‐gluco‐, and D‐galacto‐configurated phospha‐glycopyranuronates 12, 13, 21, 22, 34 and 35. Two strategies were followed. In the first one, the glucuronic acid 19 was decarboxylated to 11 and further transformed, via 20, into the trichloroacetimidate 10 (Scheme 2). Phosphorylation of 10 with (MeO)3P yielded the diastereoisomers 12 and 13, the diastereoselectivity depending on the solvent. In MeCN, 12 and 13 were obtained in a ratio of 1:1, while in non‐participating solvents the L‐ido 12 was by far the major diastereoisomer. The acetate 11 was inert to (MeO)3P, but reacted with (PhO)3P to the anomeric mixture 21/22, in keeping with a stabilizing 1,3‐interaction in the intermediate phosphonium salt. Similarly, the phospha‐galacturonates 34 and 35 were prepared from the galactoside 23 via the enol ether 26, the lactone 27, and the acetates 28/29 that were also transformed into the trichloroacetimidate 33 (Scheme 3). In the second, higher‐yielding strategy, phosphorylation of the pentodialdehyde 39 to 40/41 was followed by hydrolysis and acetylation to the phospha‐glucuronates 43/44 (Scheme 4). Transesterification to 45/46, selective deacetylation to 48/49, and formation of the trichloroacetimidates 50/51 were followed by glycosidation and deprotection to 4. The tetrazole 5 was prepared from the lactones 54/55 via the N‐benzylamides 57/58 that were treated with TfN3 to give the N‐benzyltetrazoles 59/60 (Scheme 4). These were transformed into the trichloroacetimidates 63/64, glycosylated to 65, and deprotected. The O‐carbamoylhydroximo‐lactone 7 derived from the glucuronate 67/68, and the phosphonate analogue 8 were prepared by established methods. The phosphonate 4 is slowly hydrolyzed by the E. coli β‐glucuronidase, but neither 4 nor the tetrazole 5 are affected by the bovine liver β‐glucuronidase (Table 4). The phenylcarbamate 7 of D‐glucarhydroximo‐1,5‐lactone, but not its phosphonate analogue 8, is an inhibitor (KI = 8 m̈M) of the E. coli β‐glucuronidase. The bovine liver β‐glucuronidase is inhibited strongly by 7 (IC50 = 0.2 m̈M) and weakly by 8 (IC50 = 2mM).
Synthesis and Characterization of Non‐standard Nucleosides and Nucleotides Bearing the Acceptor‐Donor‐Donor Pyrimidine Analog 6‐Amino‐3‐methylpyrazin‐2(1H)‐one
Authors: Voegel Johannes J. , Benner Steven A.
Published: December 2004

6‐Aminopyrazin‐2(1H)‐one, when incorporated as a pyrimidine‐base analog into an oligonucleotide chain, presents a H‐bond acceptor‐donor‐donor pattern to a complementary purine analog. When paired with the corresponding donor‐acceptor‐acceptor purine in oligonucleotides, the heterocycle selectively contributes to the stability of the duplex, presumably by forming a base pair of Watson‐Crick geometry joined by a non‐standard H‐bonding pattern. Aspects of the nucleoside chemistry, including syntheses of the β‐furanosyl ribonucleoside 1, the ribonucleoside triphosphate 2 and the ribonucleoside bisphosphate 3 of 6‐aminopyrazin‐2(1H)‐one are reported here. In aqueous solution, the ribonucleoside 1 was found to undergo acid‐ and base‐catalyzed rearrangement with an apparent half‐life of ca. 63 h at neutral pH and 30°. The rearrangement appears to be specific acid‐ and base‐catalyzed. The thermodynamically most stable compound formed during this rearrangement reaction was isolated by HPLC and shown to be the β‐pyranosyl form 4 of the 6‐aminopyrazin‐2(1H)‐one nucleoside in its 4C1 chair conformation. This reactivity of 1 under physiological conditions may explain why Nature does not use this particular heterocyclic system to implement an acceptor‐donor‐donor H‐bonding pattern in the genetic alphabet.
Synthesis, Molecular Recognition, and Enzymology of Oligonucleotides Containing the Non‐standard Base Pair between 5‐Aza‐7‐deazaisoguanine and 6‐Amino‐3‐methylpyrazin‐2(1H)‐one, a Donor‐Acceptor‐Acceptor Purine Analog and an Acceptor‐Donor‐Donor Pyrimidine Analog
Authors: Voegel Johannes J. , Benner Steven A.
Published: December 2004

A 6‐aminopyrazin‐2(1H)‐one (pyADD), when incorporated as a pyrimidine‐base analog into an oligonucleotide chain, presents a H‐bond acceptor‐donor‐donor pattern to 5‐aza‐7‐deazaisoguanine (puDAA), the complementrary donor‐acceptor‐acceptor purine analog. Reported here are the syntheses of the phosphoramidite of the 2′‐deoxyribonucleoside bearing the puDAA base, oligonucleotides containing this nucleoside unit, the enzyme‐assisted synthesis of oligoribonucleotides containing the pyADD ribonucleoside, and the molecular‐recognition properties of this non‐standard base pair in an oligonucleotide context. A series of melting experiments suggests that the pyADD · puDAA base pair contributes to the relative stability of a duplex structure approximately the same as an A · T base pair, and significantly more than mismatches between these non‐standard bases and certain standard nucleobases. The pyADD nucleoside bisphosphate is accepted by T4 RNA ligase, but the triphosphate of the pyADD nucleoside was not incorported by T7 RNA polymerase opposite the puDAA nucleobase in a template. Oligonucleotides containing the pyADD base slowly undergo a reversible first‐order reaction, presumably an epimerization process to give the α‐D‐anomer. These experiments provide the tools for laboratory‐based use of the pyADD · puDAA base pair as a component of an oligonucleotide‐like molecular‐recognition system based on an expanded genetic alphabet.
The Molecular and Crystal Structure of the Glycopeptide A‐40926 Aglycone
Authors: Schäfer Martina , Pohl Ehmke , Schmidt‐Bäse Karen , Sheldrick George M. , Hermann Rolf , Malabarba Adriano , Nebuloni Marino , Pelizzi Giancarlo
Published: December 2004

The crystal structure of a glycopeptide antibiotic A–40926 aglycone was investigated by X‐ray analysis at −120°. A‐40926 crystallises in the orthorhombic space group P212121 with two monomers in the asymmetric unit, a = 21.774(4), b = 28.603(7), c = 29.757(4) Å. ‘Conventional’ direct methods approach failed to solve the structure, but a novel iterative real/reciprocal space procedure was successful. Refinement against 11248 F2 data led to R1 = 13.3% for 6770 F > 4σ (F). The two monomers of A‐40926 have similar conformations and are bound by antiparallel H‐bonds to form a ‘chain’ structure of connecting dimers. The antibiotic molecule possesses a ‘binding pocket’ for the C‐terminal carboxy group of the cell‐wall protein, which is consisten with suggestions based on NMR data and the recently reported crystal structure of ureido‐balhimycin. In A‐40926 the monomers are polymerically linked by H‐bonds, quite unlike the tight dimer formation observed in ureido‐balhimycin.
Model Studies for the Coenzyme‐B12‐Catalyzed Methylmalonyl→Succinyl Rearrangement. The Importance of Hydrophobic Peripheral Associations
Authors: Darbre Tamis , Keese Reinhart , Siljegovic Vuk , Wolleb‐Gygi Annemarie
Published: December 2004

The interaction between a vitamin B12 derivative containing a peripheral C18 alkyl chain (see 1a) and a (methyl)thiomalonate substrate bearing alkyl chains of various length at the thioester group (see 5) was investigated. A catalytic cycle was established for the methylmalonyl→succinyl rearrangement by using electrochemistry and photolysis (see Scheme 3). Increased yields of the succinate relative to the reduction product were obtained (2:3 ratio), when the reaction was run in MeOH/H2O, and when both the substrate and the catalyst had an octadecyl substituent capable of hydrophobic interactions.
5,5′‐Bi‐5H‐cyclopenta[2,1‐b;3,4‐b′]dipridinylidene, a New Bridging Ligand for Metal Complexes. Preliminary Communication
Authors: Riklin Marianne , von Zelewsky Alex
Published: December 2004

5,5′‐Bi‐5H‐cyclopenta[2,1‐b;3,4‐b′]dipyridinylidene(1) was synthesized in three steps from 9,10‐phenanthroline and characterized by UV/VIS and NMR spectroscopy, mass spectrometry, and cyclic voltammetry. Its ability to act as a bridging ligand is demonstrated by the synthesis of the complexes [Ru(bpy)2(1)](PF6)2 (6) and [{Ru(bpy)2}2(1)](PF6)4 (7) (bpy = 2,2′‐bipyridine).
Total Synthesis of Cyclothialidine
Authors: Götschi Erwin , Jenny Christian‐Johannes , Reindl Peter , Ricklin Fabienne
Published: December 2004

A total synthesis of cyclothialidine (1), a new DNA gyrase inhibitor isolated from Streptomyces filipinensis, is described. The synthetic concept was tested by preparing the lactone 13 (Scheme 2) which contains the characteristic bicyclic core entity of 1. Key features of the synthesis of 1 are: preparation of 3,5‐dihydroxy‐2,6‐dimethylbenzoic acid (23) from 3,5‐dihydroxybenzoic acid (19) by two consecutive Mannich aminomethylation/hydrogenation sequences; benzylic N‐bromosuccinimide bromination of an ester derivative 25 thereof and its subsequent coupling with Boc‐Ser‐Cys‐OMe (11); cyclization of the ω‐hydroxy acid 29 29 to the 12‐membered lactone 30 using preferably Mitsunobu conditions; completion of the peptidic side chains of 1 using Boc strategy (Scheme 4). Optically pure cis‐N‐(tert‐butoxycarbonyl)‐3‐hydroxy‐L‐proline ((–)‐14) was obtained by resolution of the racemate via an efficient reaction sequence containing a lipase‐catalyzed enantiospecific acetate hydrolysis (Scheme 3). The structure of natural 1 was confirmed by comparison with the synthetic material. The synthetic route described provides also easy access to analogues of 1, e.g., via the intermediate 30.
Donor/Acceptor‐Substituted Tetraethynylethenes: Systematic Assembly of Molecules for Use as Advanced Materials
Authors: Tykwinski Rik R. , Schreiber Martin , Carlón Raquel Pérez , Diederich François , Gramlich Volker
Published: December 2004

A comprehensive series of tetraethynylethenes (= 3,4‐diethynylhex‐3‐ene‐1,5‐diynes, TEEs) bearing electrondonating (p‐methoxyphenyl or p‐aminophenyl) and/or electron‐accepting (p‐nitrophenyl) groups was prepared via [Pd]‐catalyzed Sonogashira cross‐coupling reactions. The electronic and photonic properties of these molecules were investigated with a special emphasis on the effects caused by degree and pattern of donor/acceptor substitution around the central TEE core. This analysis showed that intramolecular donor‐acceptor interactions, as evidenced by a long‐wavelength charge‐transfer band, are considerably more effective in TEEs 44 and 46, with trans and cis, linearly‐conjugated electronic pathways between donor and acceptor, than in 11, with a geminal, cross‐conjugated electronic pathway. UV/VIS Spectroscopy revealed a steady bathochromic shift of the longest‐wavelength absorption band (λmax) as the number of donor‐acceptor conjugation paths increased upon changing from bis‐arylated (11, 44, and 46) to tetrakis‐arylated (14, 31, and 35) TEEs. The position of the longest‐wavelength absorption was also found to be strongly dependent on the nature of the N‐substituents in the R2NC6H4‐donor groups. Electronic emission spectroscopic investigations demonstrated a considerable solvent dependency of the fluorescence of donor‐acceptor‐substituted TEEs such as 11 or 44, in agreement with the presence of highly polarized excited states in these molecules. Correspondingly, fluorescence spectra of TEEs bearing only donor or acceptor substituents showed little solvent dependency. The large majority of the donor/acceptor‐substituted TEEs are thermally and environmentally stable molecules. They can be stored for months as solids in the air at room temperature, and many decompose only upon heating to temperatures above 200°. X‐Ray analysis showed the conjugated C‐atom scaffolds of 44, 46, and 67 to be essentially planar, whereas the aryl substituents in 28 and 30 are rotated out of the plane of the TEE core by varying degrees.
Long‐Distance Effect on One‐Bond CC Scalar couplings upon introduction of a double bond in bicyclic systems
Authors: Jones Graeme R. , Caldarelli Stefano , Vogel Pierre
Published: December 2004

Anomalous variations of one‐bond CC scalar coupling constants are observed in going from trinorbornane‐to trinorbornene‐like structures. Most notably, a 10‐Hz increase is observed in the coupling constant involving the C‐atoms of the ethano branch facing the CC bond. An effect of about half the size is characteristic of higher homologues (bicyclo[2.2.2]octenes), but no such effect is observed for monocyclic molecules.