bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation of Chiral Building Blocks for Starburst Dendrimer Synthesis
Authors: Lapierre Jean‐Marc , Skobridis Konstantinos , Seebach Dieter
Published: December 2004

Double aldols, formally derived from acetic acid and two different aldehydes, as obtained by addition of the enolate of (R,R)‐2‐(tert‐butyl)‐6‐methyl‐1,3‐dioxan‐4‐one (A) to various aldehydes, are reduced to triols which are actually substituted chiral ‘tris(hydroxymethyl)methanes’ (see B and 3–8). Etherifications of the three OH groups of these triols with functionalized halides (allyl, 4‐(silyloxy)but‐2‐en‐l‐yl, 4‐substituted benzyl) and esterifications with pent‐4‐enoic and 3,5‐dinitrobenzyl chlorides, followed by functional group manipulations, lead to the potential center pieces 14–30 for the construction of chiral dendrimers: the building blocks prepared contain the required ‘spacers’ between the core unit, as well as three vinyl groups, three aryl bromide groups, three alcoholic or phenolic OH groups, three mesylate groups, three ester groups, or six arylamino groups at the terminus of their branches. The new compounds are all obtained on a preparative scale and are fully characterized (including elemental analysis).
Biosynthesis of the Irregular C12‐Terpenoid Dehydrogeosmin in Flower Heads of Rebutia marsoneri WERD. (Cactaceae)
Authors: Feng Zhuofu , Huber Udo , Boland Wilhelm
Published: December 2004

Farnesol (3a) is the precursor to the irregular C12 terpenoid (4S, 4aS, 8aS)‐1,2,3,4,4a,5,8,8a‐octahydro‐4,8a‐dimethylnaphthalen‐4a‐ol (= dehydrogeosmin; 1). The irregular C‐backbone originates from the oxidative removal of a C3 side chain from a C15 eudesmane‐type intermediate (Scheme 2). The bicyclic C‐framework is assembled by a formal addition of H2O across the endocyclic double bonds of a monocyclic germacradiene‐type precursor. The biosynthetic pathway follows from administration of the deuteriated farnesols 3b–e to flower heads of the cactaceae Rebutia marsoneri Werd. and mass‐spectroscopic analysis of the collected volatiles.
Complexes of the Triolide from (R)‐3‐Hydroxybutanoic Acid with Sodium, Potassium, and Barium Salts: Crystal Structures, Ester Chelates and Ester Crowns, Crystal Packing, Bonding, and Electron‐Localization Functions
Authors: Seebach Dieter , Bürger H. Michael , Plattner Dietmer A. , Nesper Reinhard , Fässler Thomas
Published: December 2004

The triolide of (R)‐3‐hydroxybutanoic acid ((R,R,R,))‐3,7,11‐trimethyl‐2,6,10‐trioxadodecane‐1,5,9‐trione; (1), readily available from the corresponding biopolymer P(3‐HB) in one step, forms crystalline complexes with alkali and alkaline earth salts. The X‐ray crystal structures of three such complexes, (3 NaSCN)·4 1 (2), (2 KSCN)·2 1 · H2O (3), and (2) Ba(SCN)2 · 2 1 · 2 H2O · THF (4), have been determined and are compared. The triolide is found in these structures (i) as a free molecule, making no contacts with a cation (clathrate‐type inclusion), (ii) as a monodentate ligand coordinated to a single ion with one carbonyl O‐atom only, (iii) as a chelator, forming an eight‐membered ring, with two carbonyl O‐atoms attached to the same ion, (iv) as a linker, using two carbonyl O‐atoms to bind to the two metals of an ion‐X‐ion unit (ten‐membered ring), and (v), in a crown‐ester complex, in which an ion is sitting on the three unidirectional CO groups of a triolide molecule (Figs. 1–3). The crystal packing is such that there are columns along certain axes in the centers of which the cations are surrounded by counterions and triolide molecules, with the non‐polar parts of 1 on the outside (Fig. 4). In the complexes 2–4, the triolide assumes conformations which are slightly distorted, with the carbonyl O‐atoms moved closer together, as compared to the ‘free’ triolide 1 (Fig. 5). These observed features are compatible with the view that oligo (3‐HB) may be involved in the formation of Ca polyphosphate ion channels through cell membranes. A comparison is also made between the triolide structure in 1–4 and in enterobactin, a super Fe chelator (Fig. 5). To better understand the binding between the Na ion and the triolide carbonyl O‐atoms in the crown‐ester complex, we have applied electron‐localization function (ELF) calculations with the data set of structure 2, and we have produced ELF representations of ethane, ethene, and methyl acetate (Figs. 6–9). It turns out that this theoretical method leads to electron‐localization patterns which are in astounding agreement with qualitative bonding models of organic chemists, such as the ‘double bond character of the COOR single bond’ or the ‘hyperconjugative n → σ* interactions between lone pairs on the O‐atoms and neighbouring σ‐bonds’ in ester groups (Fig. 8). The noncovalent, dipole/pole‐type character of bonding between Na+ and the triolide carbonyl O‐atoms in the crown‐ester complex (the NaOC plane is roughly perpendicular to the OCO plane) is confirmed by the ELF calculation; other bonding features such as the CN bond in the NaSCN complex 2 are also included in the discussion (Fig. 9).
Catalytic Enantioselective Hydrosilylation of Aromatic Ketones Using Rhodium Complexes of TADDOL‐Derived Cyclic Phosphonites and Phosphites
Authors: Sakaki Jun‐ichi , Schweizer W. Bernd , Seebach Dieter
Published: December 2004

Cyclic phosphonites and phosphites2–4are readily available from Cl2PR and (R,R)‐ or (S,S)‐α,α,α′,α′‐tetraaryl‐1,3‐dioxolane‐4,5‐dimethanols (= TADDOLs1, which, in turn, are only two steps away from tartrate); the X‐ray crystal structure of one representative, the phenyl phosphonite2b, was determined. Five previously described and six new ones of the chiral P derivatives were tested as ligands for RhI‐ and PdO‐catalyzed reactions such as hydrocarbonylations, hydroborations, and hydrosilylations of CC bonds; while the resulting catalysts were highly active and regioselective, they did not lead to useful enantiomer enrichment in the products (Scheme 1). In contrast, hydrosilylation of phenyl and 2‐naphthyl methyl or ethyl ketone by Ph2SiH2(1.2 equiv.) gave, after desilylation, the corresponding secondary alcohols of (R)‐configuration with up to 87% ee in the presence of 0.1 equiv. of the penta(2‐naphthyl)‐substituted phosphonite3dand 0.02 mol‐equiv. of Rh (Table 1).
A Novel Synthesis of 2,2‐Disubstituted 3‐Amino‐2H‐azirines Based on the Reaction between Amide Enolates and Diphenyl Phosphorochloridate
Authors: Villalgordo José M. , Heimgartner Heinz
Published: December 2004

A novel synthesis of 2,2‐disubstituted 3‐amino‐2H‐azirines based on the reaction between amide enolates and diphenyl phosphorochloridate (DPPCl), followed by treatment with NaN3 is presented. The yields obtained in general are excellent, and the method is suitable for laboratory‐scale preparations as well as for larger amounts.
Determination of the Absolute Configuration of Dimethyl (2S,3S)‐2‐Allyl‐3‐hydroxyglutarate: A Chiral Building Block for Preparing Branched‐Chain Nucleoside Analogues
Authors: Arslan Tuncer , Herradon Bernardo , Schweizer Bernd W. , Benner Steven A.
Published: December 2004

A yeast‐catalyzed reduction of dimethyl (2S,3S)‐2‐allyl‐3‐hydroxyglutarate is the key step in the preparation of bis‐homo, branched‐chain nucleoside analogues. To establish unambiguously the stereochemical course of the microbial reaction, the product has been converted to a derivative esterified with camphanoyl chloride, and a crystal structure of the derivative solved.
Oceanapins A–F, Unique Branched Ceramides Isolated from the Haplosclerid Sponge Oceanapia cf. tenuis of the Coral Sea
Authors: Mancini Ines , Guella Graziano , Pietra Francesco , Debitus Cécile
Published: December 2004

A series of ceramides, called oceanapins A–F (2–7), which are unique for branching at both the sphingosine and fatty‐acid chains, have been isolated as pure compounds from the haplosclerid sponge Oceanapia cf. tenuis of the Coral Sea. Following acid hydrolysis, both the fatty‐acid and the sphingosine portions were obtained separately, which allowed their unequivocal structural definition. The absolute configuration was secured via protection of C(1′)–OH and Mosher's esterification at C(3′)–OH of the oceanapins.
Radical Cations of Tetrazinodi(heteroarenes): An ESR and ENDOR Study
Authors: Gerson Fabian , Lamprecht Axel
Published: December 2004

14N‐ and 1H‐Coupling constants, determined by ESR, ENDOR, and general‐TRIPLE‐resonance spectroscopy, are reported for the radical cations of tetrazinodi(heteroarenes) 1–8. The results comply with the expectation that donor properties of these compounds are mainly due to the electron‐rich dihydrotetrazine ring.
Die Synthese von Azaisomeren des Triesters von PQQ: 3H‐Pyrrolo[3,2‐f]‐, 1H‐Pyrrolo[3,2‐h]‐ und 7H‐Pyrrolo[2,3‐h]chinolinchinon‐Derivate
Authors: Martin Pierre , Winkler Tammo
Published: December 2004

The Synthesis of Azaisomers of the Triester of PQQ: 3H‐Pyrrolo[3,2‐f]‐, 1H‐Pyrrolo[3,2‐h]‐, and 7H‐Pyrrolo[2,3‐h]quinolinequinone Derivatives

We describe here the synthesis of the title compounds 3–5, starting from highly substituted aminoindoles. The annelated pyridine rings were built up in each case with dimethyl 4‐oxoglutaconate according to Corey's procedure. All three o‐quinone derivatives 3–5 are stable compounds, comparable to PQQ‐triester. The azaisomers vary in biological activity from practically inactive to strong inhibition of the α‐amidating enzyme or the ornithin decarboxylase.
FT‐IR Investigation of Rare‐Earth and Metal‐Ion Solvation. Part 14. Interaction between uranyl perchlorate and dimethyl sulfoxide in anhydrous acetonitrile
Authors: Bünzli Jean‐Claude G. , Metabanzoulou Jean‐Pierre
Published: December 2004

The interaction between the uranyl ion and perchlorate in anhydrous acetonitrile has been investigated by FT‐IR and Raman spectroscopy. Vibrations assigned to uncoordinated (u), monodentate (m), and bidentate (b) perchlorate anions were identified in 0.075M solutions. Quantitative data indicate that perchlorate is distributed as follows: 37 ± 2% are uncoordinated, 36 ± 7% are monodentate, and 27 ± 7% are bidentate. This is in agreement with the conductivity of the solutions which is at the lower end of the range accepted for 1:1 electrolytes. The splittings v4–v1(m) and v8–v1(b) of 147 and 246 cm−1, respectively, point to a large inner‐sphere interaction. An equilibrium occurs between two differently coordinated species. Various amounts of DMSO were added to 0.05M perchlorate solutions (R′ = [DMSO]t/[UO]t = 1–10). The v7 (SO) and v22 (CS) vibrations of DMSO were used to determine the average number of coordinated DMSO molecules per uranyl ion, which is close to 4. Some bidentate perchlorate ions are still present in these solutions, but all the MeCN molecules (2.6 on average) are expelled out of the inner coordination sphere. The data can again be interpreted in terms of an equilibrium between differently coordinated species. The average coordination number of the uranyl ion is 4.4, as the perchlorate salt in MeCN solution, and may be somewhat smaller in the presence of DMSO. The possible presence of dimeric species is also discussed.
Preparation of Boc‐Amino‐Acid or Peptide Aldehydes via Reduction of Corresponding Phenyl Esters
Authors: Zlatoidsky Pavol
Published: December 2004

A new alternative method for the preparation of amino‐acid and peptide aldehydes based on reduction of corresponding phenyl esters with lithium tri(tert‐butoxy)aluminium hydride is described.
Short Optimally Capped Duplex DNA as Conformationally Restricted Analogue of B‐DNA
Authors: Bannwarth Willi , Dorn Arnulf , Iaiza Patrick , Pannekouke Xavier
Published: December 2004

We describe the synthesis of short double‐stranded DNA fragments (see 4 and 13) which are capped on both ends by an optimally designed linker molecule. The new structures are stable with respect to hybrid dissociation and should have implications in physical studies involving double‐stranded DNA as well as in the antisense area for the specific modulation of gene expressions.
Synthesis of 2′‐Deoxyisoinosine and Related 2′‐Deoxyribonucleosides
Authors: Seela Frank , Chen Yaoming , Bindig Uwe , Kazimierczuk Zygmunt
Published: December 2004

Various 2‐substituted purine and pyrrolo[2,3‐d]pyrimidine 2′‐deoxyribonucleosides with methylthio (13a), chloro (13b), methoxy (9b), and oxo (2, 3) substituents at C(2) are prepared. They are obtained eitherviastereoselective nucleobase‐anion glycosylation or by base transformation. A three‐step synthesis of the unknown 2′‐deoxyisoinosine (2) from 2′‐deoxyguanosine (15) is described. Compound2as well as its 7‐deazapurine derivative3exhibit strong fluorescence.
Synthesis of (R)‐ and (S)‐5‐(Hydroxymethyl)‐3‐isopropyloxazolidin‐2‐one, intermediates in the preparation of optically active β‐blockers
Authors: Warmerdam Erwin G. J. C. , Brussee Johannes , van der Gen Arne , Kruse Chris G.
Published: December 2004

The (R)‐ and (S)‐5‐(hydroxymethyl)‐3‐isopropyloxazolidin‐2‐ones, ((R)‐ and (S)‐2, resp.), pivotal intermediates in the preparation of optically active β‐blockers, were synthesized using (R,E)‐2‐hydroxypent‐3‐enenitrile (1) as the chiral starting material. In the synthesis of (R)‐2, a known cyclization/inversion step was applied.
Glycosylidene Carbenes. Part 14. Glycosidation of partially protected galactopyranose‐, glucopyranose‐, and mannopyranose‐derived vicinal diols
Authors: Muddasani Pulla Reddy , Bozó Eva , Bernet Bruno , Vasella Andrea
Published: December 2004

The relation between H‐bonding in diequatorial trans‐1,2 and axial, equatorial cis‐1,2‐diols and the regioselectivity of glycosidation by the diazirine 1 was examined. H‐Bonds were assigned on the basis of FT‐IR and 1H‐NMR spectra (Fig. 1). Glycosidation by 1 of the gluco‐configurated diequatorial trans‐2,3‐diols 4–7 yielded the mono‐glucosylated products 16/17/20/21 (69–89%); 1,2‐/1,3‐linked products (37–46:63–54), 24/25/28/29 (60–63%; 1,2‐/1,3‐linked products 46–51:54–49), 32–35 (69–94%; 1,2‐/1,3‐linked products 45–52:55–48), and 36/37/40/41 (59–63%; 1,2‐/1,3‐linked products 52–59:48–41), respectively (Scheme 1, Table 3). The disaccharides derived from 4, 5, and 7 were characterized as their acetates 18/19/22/23, 26/27/30/31, and 38/39/42/43, respectively. Glycosidation of the galacto‐configurated diequatorial 2,3‐diols 8 and 9 and the manno‐configurated diequatorial 3,4‐diol 10 by 1 (Scheme 2, Table 3) also proceeded in fair yields to give the disaccharides 44–47 (69–80%;1,2‐/1,3‐linked products ca. 1:1), 48–51 (51–61%;1,2/‐1,3‐linked products 54–56:56–54), and 56/57/60/61 (71–80%; 1,3‐/1,4‐linked products 49–54:51–46), respectively. The 1,3‐linked disaccharides 56/57 derived from the diol 10 were characterized as the acetates 58/59. The regio‐ and stereoselectivities of the glycosidation by 1 were much better for the α‐D‐manno‐configurated axial, equatorial cis‐2,3‐diol 11 and the galacto‐configurated axial, equatorial cis‐3,4‐diol 13 (1,2‐/1,3‐linked disaccharides ca. 3:7 for 11 and 1,3‐/1,4‐linked disaccharides ca. 4:1 for 13; Scheme 3, Table 4). The regio‐ and stereoselectivity for the β‐D‐manno‐configurated cis‐2,3‐diol 12 were, however, rather poor (1,2‐/1,3‐linked products 48:52). The 1,2‐linked disaccharides 66/67 derived from 12 were characterized as the acetates 70/71. Koenigs‐Knorr‐type glycosidation of the cis‐diols 11–13 by 2 or 3 proceeded with a similar regio‐ and a higher stereoselectivity (α‐D > β‐D with the donor 2 and α‐D < β‐D with the donor 3) than with 1, with the exception of 12 which did not react with 2. The regioselectivity of the glycosidations by 1 agrees fully with the H‐bonding scheme of the diols and with the hypothesis that the intermediate carbene is preferentially protonated by the most weakly H‐bonded OH group. The regioselectivity of the glycosidation by 2 and by 3 is determined by a higher reactivity of the equatorial OH groups and by H‐bonding. Several H‐bonded and equilibrating isomers of a given diol may intervene in the glycosidation by 1, or by 2 and 3, resulting in the same regioselectivity. The low nucleophilicity of 12 and the low degree of regioselectivity in its reaction with 3 show that stereoelectronic effects may also profoundly influence the nucleophilicity of OH groups.
Glycosylidene Carbenes. Part 15. Synthesis of disaccharides from allopyranose‐derived vicinal 1,2‐diols. Evidence for the protonation by a H‐bonded hydroxy group in the σ‐plane of the intermediate carbene, followed by attack on the oxycarbenium ion in the π‐plane
Authors: Muddasani Pulla Reddy , Bernet Bruno , Vasella Andrea
Published: December 2004

The α‐D‐allo‐diol 9 possesses an intramolecular H‐bond (HOC(3) to OC(1)) in solution and in the solid state (Fig. 2). In solution, it exists as a mixture of the tautomers 9a and 9b (Fig. 3), which possess a bifurcated H‐bond, connecting HOC(2) with both OC(1) and OC(3). In addition, 9a possesses the same intramolecular H‐bond as in the solid state, while 9b is characterized by an intramolecular H‐bond between HOC(3) and OC(4). In solution, the β‐D‐anomer 12 is also a mixture of tautomers, 12a and presumably a dimer. The H‐bonding in 9 and 12 is evidenced by their IR and 1H‐NMR spectra and by a comparison with those of 3–8, 10, and 11. The expected regioselectivity of glycosidation of 9 and 12 by the diazirine 1 or the trichloroacetimidate 2 is discussed on the basis of the relative degree of acidity/nucleophilicity of individual OH groups, as governed by H‐bonding. Additional factors determining the regioselectivity of glycosidation by 1 are the direction of carbene approach/proton transfer by H‐bonded OH groups, and the stereoelectronic control of both the proton transfer to the alkoxy‐alkyl carbene (in the σ‐plane) and the combination of the thereby formed ions (π‐plane of the oxycarbenium ion). Glycosidation of 9 by the diazirine 1 or the trichloroacetimidate 2 proceeded in good yields (75–94%) and with high regioselectivity. Glycosidation of 9 and 12 by 1 or 2 gave mixtures of the disaccharides 14–17 and 18–21, respectively (Scheme 2). As expected, glycosidation of 12 by 1 or by 2 gave a nearly 1:1 mixture of regioisomers and a slight preference for the β‐D‐anomers (Table 4). Glycosidation of the α‐D‐anomer 9 gave mostly the 1,3‐linked disaccharides 16 and 17 (α‐D β‐D) along with the 1,2‐linked disaccharides 14 and 15 (α‐D < β‐D, 1,2‐/1,3‐linked glycosides ca. 1:4), except in THF and at low temperature, where the β‐D‐configurated 1,2‐linked disaccharide 15 is predominantly formed. Similarly, glycosidation of 9 with 2 yielded mainly the 1,3‐linked disaccharides (1,2‐/1,3‐linked products ca. 1:3 and α‐D/β‐D ca. 1:4). Yields and selectivity depend upon the solvent and the temperature. The regioselectivity and the unexpected stereoselectivity of the glycosidation of 9 by 1 evidences the combined effect of the above mentioned factors, which also explain the lack of regio‐complementarity in the glycosidation of 9 by 1 and by 2 (Scheme 3). THF solvates the intermediate oxycarbenium ion, as evidenced by the strong influence of this solvent on the regio‐ and stereoselectivity, particularly at low temperatures, where kinetic control leads to a stereoelectronically preferred axial attack of THF on the oxycarbenium ion.
An ‘Umpolung’ Route to Peptide Mimetics of Thyrotropin‐Releasing Hormone based on a cyclohexane framework
Authors: Bös Michael , Olson Gary L. , Vincent George P.
Published: December 2004

Peptide mimetics of thyrotropin‐releasing hormone (TRH) in which the peptide backbone is replaced by cyclohexane were synthesized from the cyclohexenone precursor 7. The aromatic side chains of the mimetics were derived from the corresponding aldehydes which were attached to the cyclohexenone via the Wittig reagent 8. The TRH mimetics are active in a mouse model of cognitive performance.
Variable‐Temperature and ‐Pressure 31P‐NMR Study of the Intramolecular PPh3 Migration in the Cluster Compound [Ir2Rh2(CO)11PPh3]
Authors: Laurenczy Gábor , Bondietti Giacomo , Merbach André E. , Moullet Bertrand , Roulet Raymond
Published: December 2004

The reaction of [Ir2Rh2(CO)12] with 1 mol‐equiv. of PPh3 yields [Ir2Rh2(CO)11PPh3] (1) as a mixture of two isomers with the phosphine ligand axially bound either to one basal Rh‐atom in the kinetically preferred isomer 1 R or to one basal Ir‐atom in the thermodynamically preferred isomer 11. Both isomers are fluxional on the 13C‐NMR time scale at low temperature due to CO scrambling. Around room temperature, a new type of fluxional process starts to operate which is responsible for the isomerisation 1R⇄11, i.e. the intramolecular migration of the reputedly inert PPh3 ligand from one metal centre to another. The activation volumes of conversions 1R → 11 and 11 → 1R are both positive, indicating that the migration of PPh3 is dissociative in character. This article reports the first application of variable pressure 31P‐NMR to mechanistic studies.
Stable Quinone Methides: Regioselective para‐Oxidation of a 2,4‐bis[(alkylthio)methyl]phenol and addition reactions to quinonemethides
Authors: Meier Hansrudolf , Kuenzi Hanspeter , Fuhrer Hermann , Rist Günther
Published: December 2004

The 2,4‐bis‐functionalized phenol 1 is dehydrogenated regioselectivity with potassium ferricyanide, affording the corresponding p‐quinonemethide 2. Hydrolysis of 2 affords a mixture of dithioacetal 5a and benzaldehyde 6; 1,6‐addition of thiols to 2 gives the dithioacetals 5 of benzaldehyde 6; reaction of 2 with 2,2′‐azobis(isobutyronitrile) (= 2,2′‐dimethyl‐2,2′‐azobis(propanenitrile)) leads to 9a, 9b, and 10, addition products of the 1‐cyano‐1‐methylethyl radical. The structures of all products are confirmed mainly by 1H‐ and 13C‐NMR spectroscopy, and the mode of their formation is discussed.
Aldehyde Intermediates in the Synthesis of Tacamine‐Type Indole Alkaloids: Preparation of (±)‐apotacamine
Authors: Tolvanen Arto , Belle David Din , Lounasmaa Mauri
Published: December 2004

The synthesis of aldehyde intermediates suitable for the preparation of indole alkaloids of the tacamine (1) type is described. The four possible aldehydes 4–7 were prepared from methyl 5‐ethylnicotinate (8) in a few simple steps using a base‐catalyzed epimerization as the final step (Schemes 1 and 2). The key aldehyde 4, which is an analogue of the important vincamine intermediate 3 (‘Oppolzer's aldehyde’), was finally converted into the indole alkaloid (±)‐apotacamine (21).
Nucleic‐Acid Analogues with Restricted Conformational Flexibility in the Sugar‐Phosphate Backbone (‘bicyclo‐DNA’). Part 3. Synthesis, pairing properties, and calorimetric determination of duplex and triplex stability of decanucleotides from [(3′S,5′R)‐2′‐deoxy‐3′,5′‐ ethano‐β ‐D‐ribofuranosyl]adenine and ‐thymine
Authors: Tarköy Markus , Bolli Martin , Leumann Christian
Published: December 2004

The synthesis of a new type of oligonucleotide (‘bicyclooligodeoxynucleotide’ = bcd(Xn)) displaying less conformational flexibility in its sugar‐phosphate backbone is described, and a characterization of the pairing properties and energetics of the decamers bcd(T10) and bcd (A10) with each other and with complementary RNA and DNA sequences by UV‐spectroscopic and calorimetric techniques is given. The results can be summarized as follows: (i) bcd(T10) pairs less strongly to complementary RNA and DNA, whereas bcd(A10) forms stronger duplexes relative to the natural system. (ii) bcd(A10) discriminates between a complementary oligodeoxynucleotide with a mismatch in the center in the same way as d(A10), indicating equal base‐pairing selectivity. (iii) bcd(A10) forms more stable triplexes with d(T10) of the pyrimidine‐purine‐pyrimidine (py · pu · py) motif than d(A10). (iv) The stability of duplexes containing a bicyclic strand is more sensitive towards salt concentration. The higher sensitivity in bcd(A10) containing duplexes is due to a higher differential cation uptake. (v) Differential scanning calorimetric (DSC) analysis of duplex‐formation enthalpies shows ΔHvH in all duplexes containing bicyclooligonucleotides to be more negative than ΔHcal, which is compatible with the formation of catenated structures. (vi) Isothermal titration calorimetry (ITC) provides a complete set of thermodynamic data including duplex and triplex association constants for the systems d(A10)/d(T10), bcd(A10)/d(T10), d(A10)/bcd(T10), bcd(A10)/bcd(T10). (vii) All duplexes containing bicyclic strands show a (numerically) reduced pairing entropy term with respect to that of the natural system. (viii) Enthalpies from DSC and ITC are similar, suggesting that the enthalpic contribution from ordered single strands to the overall duplex‐formation enthalpy plays a minor role in the duplexes investigated.
Intramolecular Dynamics of Tetranuclear Iridium Carbonyl Cluster Compounds. Part V. Polysubstituted derivatives of [Ir4(CO)12]
Authors: Strawczynski Andrés , Hall Chris , Bondietti Giacomo , Ros Renzo , Roulet Raymond
Published: December 2004

The dynamic behaviour of twelve polysubstituted derivatives of [Ir4(CO)12] has been investigated in solution, using 2D‐EXSY, and VT‐31P‐ and 13C‐NMR. [Ir4(CO)6(μ2‐CO)3(η4‐diarsine) PPh3] and [Ir4(CO)6(μ2‐CO)3(η4‐nor‐bornadiene)(PMePh2)] exhibit two isomeric forms in solution, which interconvert through an intramolecular change of basal face. The related cluster [Ir4(CO)6(μ2‐CO)3(η4‐norbornadiene)PPh3] exists as a single isomer in solution. It displays rotation of CO ligands about the apical Ir‐atom, followed by two consecutive changes of basal face. The tetrasubstituted clusters with two chelating ligands [Ir4(CO)5(μ2‐CO)3(η4‐diolefin)2] also exhibit rotation of apical CO's, the activation energy increases with greater steric hindrance of the radical ligands. A quantitative analysis of the 31P‐ and 13C‐2D‐EXSY spectra followed by simulation of the corresponding VT‐NMR spectra of [IR4(CO)5(μ2‐CO)3(μ2‐L)2] (L = bis(diphenylphosphino)methane and 1,3‐bis(diphenylphosphino)propane) revealed a pairwise averaging of the P‐atoms, caused by two parallel changes of basal face averaging all CO ligands. In addition, the restricted rotation of ligands about the apical Ir‐atom was identified at higher temperatures. The remaining clusters are either rigid on the NMR time scale, or display CO‐scrambling about a single Ir‐atom.
Synthesis and Evaluation as Irreversible Glycosidase Inhibitors of Mono‐ and Oligo(glycosylthio)benzoquinones
Authors: Schnabelrauch Matthias , Vasella Andrea , Withers Stephen G.
Published: December 2004

The mono(glucosylthio)hydroquinone 2 was prepared by S‐glycosidation of 2‐mercaptobenzene‐1,4‐diol and by addition of the acetylated 1‐thioglucose 3 to benzo‐1,4‐quinone (Scheme 1). The second, higher yielding procedure was adopted for the preparation of a range of (glucosylthio)hydroquinones. Addition of 3 to 2‐chlorobenzo‐1,4‐quinone, followed by oxidation gave the 1‐thioglucosides 7 and 12 (1.3:1), while addition of HCl to the (glucosylthio)quinone 4 and oxidation gave mainly 12 (Scheme 1). Similarly, the bis(glucosylthio)hydroquinone 33 was obtained from 3 and 4 (Scheme 4), and the (cellobiosylthio)hydroquinone 18 from the thiol 16 and benzo‐1,4‐quinone (Scheme 2). Addition of the 4‐thioglucoside 21 to benzo‐1,4‐quinone (→22) and to 4 was followed by oxidation to yield the mono(glucosylthio)quinone 23 and the disubstituted quinones 24 and 25, respectively (Scheme 3). A mixture 24/25 was also obtained from the addition of 3 to 23. The tris(glucosylthio)hydroquinone 36 was obtained by addition/elimination to the dichloroquinone 29 or the dimesylate 31, which was prepared in a simplified way (Scheme 4). The tetrakis(glucosylthio)hydroquinone 37 was obtained from 3 and chloranil, followed by reduction. The acylated hydroquinones were deprotected (→5, 9, 14, 19, 27, 34, and 38), and oxidized to the corresponding quinones (6, 10, 15, 20, 28, 35, and 40). The (glucosylthio)quinones 6, 15, 20, 28, and 35 were tested as time‐dependent inactivators of a retaining β‐1,4‐glucosidase from Agrobacterium faecalis (Abg), which has a strong exo‐glucosidase action (Table 1). Similarly, compounds 20, 28, and 35 were tested with a cellulase from Cellulomonas fimi (Cex) which degrades cellulose and cellooligosaccharides by hydrolysis of a cellobiose unit from the nonreducing terminus. The most effective inactivators for Abg were 6, 15, and 35, which inactivated this enzyme with similar second‐order rate constants. (Glycosylthio)quinone 28 was the worst inactivator and did not show normal saturation behaviour. Inactivation of Cex by the (glycosylthio)quinones was 3–500 times slower than that of Abg. The three inactivators 20, 28, and 35 had approximately the same efficacy with Cex, suggesting that they bind to this enzyme in a similar mode. Further, the Ki values observed are very similar to Km values measured for aryl cellobiosides, implying that they bind at the active site.
The Influence of the Axial Chirality of Dibenzo[a,c]cyclooctene on the Configuration of Its Photo‐Diels‐Alder Adducts
Authors: Burger Ulrich , Lottaz Pierre‐André , Millasson Patricia , Bernardinelli Gérard
Published: December 2004

Triazole‐diones and naphthoquinone are shown to add in a photochemical [4+2] reaction to the strongly twisted title diene 1. With 1, 4‐naphthoquione, the process is also accompanied by a [2+2] cycloaddition. When the pure atropisomer (−)‐1 is irradiated in presence of 2, 3‐dichloro‐ 1, 4‐naphthoquinone (9), the axial chirality of the diene is preserved. Moreover, it is found to exert complete control over the chirality induced in the resulting spiro‐dihydropyrane 10. Absolute configuration are determined by X‐ray crystallography. In absence of a photo‐dienophile, the axially chiral, dextrorotatory 6‐phenyldibenzo[a,ccyclootene] ((++)‐11) undergoes a stereospecific electrocyclization to give levorotatory 4b,6a‐dihydro‐5‐phenylcyclobuta[l]phenanthrene ((−)‐13). Thus, only one out of two possible, disrotatory modes of ring closure is preferred.
Nucleosides. Part LVI. Aminolysis of carbamates of adenosine and cytidine
Authors: Sigmund Harald , Pfleiderer Wolfgang
Published: December 2004

The 2‐(4‐nitrophenyl)ethoxycarbonyl(npeoc) group, introduced 1984 as protecting group for exocyclic amino functions of nucleic‐acid bases, reacts with amines under mild conditions to urea derivatives. Treatment of 2′,5′‐di‐O‐acetyl‐N6‐[2‐(4‐nitrophenyl) ethoxycarbonyl]cordycepin (3) with NH3/MeOH overnight at room temperature affords cordycepin (4) and N6‐carbamoylcordycepin (5). Preliminary investigations towards the elucidation of the reaction mechanism indicate that the aminolysis proceeds via an addition‐elimination or an isocyanate mechanism, depending on the reaction conditions. The phenoxycarbonyl (phoc) group at N6 or N4 was chosen to study the mild conversion of carbamates with aromatic amines into ureas of adenosine and cytidine, respectively.
Preparation of Oxazolidine‐Containing Peptides: Unusual effects in RhIII‐catalyzed acetalizations of aldehydes with urethane‐protected serine and threonine esters and with dipeptides containing serine or threonine residues at the N‐terminus
Authors: Seebach Dieter , Sommerfeld Thimo L. , Jiang Qiongzhong , Venanzi Luigi M.
Published: December 2004

The cyclization reaction of aldehydes with Z‐ and Boc‐protected β‐hydroxyamino‐acid esters (Tables 1 and 2), or of dipeptides containing serine or threonine at the N‐terminus (Table 3), to give oxazolidine derivatives, occurs in the presence of isopropyl orthoformate and catalytic amounts of [Rh(MeCN)3(triphos)](CF3SO3)3. The reaction may be carried out under kinetic or under thermodynamic control, so that the ratio of the two possible epimeric products can be changed. The protecting group can be removed from the 3‐position of the oxazolidine ring, and the resulting NH group can be coupled with another amino acid. Thus, a new method for the preparation of peptides containing β‐hydroxy‐amino acid‐derived oxazolidines (‘pseudo‐prolines’) is available. N‐Neopentyl‐substituted tripeptides are also described.
Synthetic Attempts towards ‘Aromatic’ Nonafulvenes
Authors: Chai Shengyong , Neuenschwander Markus
Published: December 2004

According to their spectroscopic behavior, four classes of nonafulvenes may be distinguished, but, so far, only three classes have been identified. Type‐A nonafulvenes (including parent 1a) are typically olefinic molecules with strongly alternating bond lengths and a nonplanar nine‐membered ring. Type‐B nonafulvenes are characterized by four pairs of equivalent ring H‐atoms and ring C‐atoms. Spectra of both Type‐A and Type‐B nonafulvenes are not dependent on temperature and solvent polarity. However, spectra of Type‐C nonafulvenes (including prototype 1d with R1 = R2 = NMe2) are strongly influenced by temperature and solvent polarity due to an equilibrium 1⇄1± between the nonpolar olefinic 1 and dipolar planarized 1±. So far, Type‐D nonafulvenes occurring exclusively in the dipolar form 1± were unknown. Synthetic attempts towards nonafulvenes of Type D are described and problems encountered in nonafulvene syntheses are discussed. Several new cyclononatetraenes and four new nonafulvenes (or nonafulvalenes) 31, 1n, 3, and 5 have been synthesized. Spectroscopic evidence shows that 11,12‐bis(diethylamino)nonatriafulvalene 5 is the first Type‐D nonafulvene.
Synthesis of Benzazepine Analogues of Noscapine
Authors: Schmidhammer Helmut , Scherb‐Bukowiecki Eva , Mayer Thomas A. , Schönholzer Peter
Published: December 2004

The synthesis of benzazepine analogues of the opium alkaloid noscapine (1) is described. The benzazepines 2 and 3 were prepared starting from nornarceine ethyl ester (4; readily available from 1) in several steps. X‐Ray analysis of compound 2 revealed that it is not a diastereosisomer mixture but a racemate of the threo‐form and thus has the same configuration as 1.
Synthesis of Enantiomerically Pure Ferrocenes from Glycofuranosyl‐cyclopentadienes, synthetic equivalents of (alkoxyalkyl)fulvenes
Authors: Vedø Per , Chauvin Rémi , Li Zhi , Bernet Bruno , Vasella Andrea
Published: December 2004

Cyclopentadienyl C‐glycosides (= glycosyl‐cyclopentadienes) have been prepared as latent fulvenes. Their reaction with nucleophiles leads to cyclopentadienes substituted with (protected) alditol moieties and, hence, to enantiomerically pure metallocenes. Treatment of 1 with cyclopentadienyl anion gave the epimeric glycosyl‐cyclopentadienes 6/7 (Scheme 1). Each epimer consisted of a ca. 1:1 mixture of the 1, 3‐and 1, 4‐cyclopentadienes a and b, respectively, which were separated by prep. HPLC. Slow regioisomerisation occurred at room temperature. Diels‐Alder addition of N‐phenylmaleimide to 6a/b ca. 3:7 at room temperature yielded three ‘endo’‐adducts, i.e., a disubstituted alkene (8 or 9, 25%) and the trisubstituted alkenes 10 (45%) and 11 (13%). The structure of 10 was established by X‐ray analysis. Reduction of 6/7 (after isolation or in situ) with LiAlH4 gave the cyclopentadienylmannitols 12a/b (80%) which were converted to the silyl ethers 13a/b (Scheme 2). Lithiation of 13a/b and reaction with FeCl2 or TiCl4 led to the symmetric ferrocene 14 (76%) and the titanocene 15 (34%), respectively. The mixed ferrocene 16 (63%) was prepared from 13a/b and pentamethylcyclopentadiene. Treatment of 6/7 with PhLi at −78° gave a 5:3 mixture of the 1‐C‐phenylated alcohols 17a/b and 18a/b (71%) which were silylated to 19a/b and 20a/b, respectively. Lithiation of 19/20 and reaction with FeCl2 afforded the symmetric ferrocenes 21 and 22 and the mixed ferrocene 23 (54:15:31, 79%) which were partially separated by MPLC. The configuration at C(1) of 17–22 was assigned on the basis of a conformational analysis. The reaction of the ribofuranose 24 with cyclopentadienylsodium led to the epimeric C‐glycosides 27a/b and 28a (57%, ca. 1:1, Scheme 3). The in‐situ reduction of 27/28 with LiAlH4 followed by isopropylidenation gave 25a/b (65%) which were transformed into the ferrocene 26 (79%) using the standard method. Phenylation of 27/28, desilylation, and isopropylidenation gave a 20:1 mixture of 33a/b and 34a/b (86%) which was separated by prep. HPLC. The same mixture was obtained upon phenylation of the fulvene 32 which was obtained in 36% yield from the reaction of the aldehydo‐ribose 30 with cyclopentadienylsodium at −100°. Lithiation of 33/34 and reaction with FeCl2 gave the symmetric ferrocene 35 (88%). Similarly, the aldehydo‐arabinose 36 was transformed via the fulvene 37 (32%) into a 18:1 mixture of 38a/b and 39a/b (78%) and, hence, into the ferrocene 40 (83%). Conformational analysis allowed to assign the configuration of 33–35, whereas an X‐ray analysis of 40 established the (1S)‐configuration of 38a/b and 40. The opposite configuration at C(1) of 38a/b and 33a/b was established by chemical degradation (Scheme 4). Hydrogenation (→41 and 44, resp.), deprotection (→ 42 and 45, resp.), NaIO4 oxidation, and NaBH4 reduction yielded (+)‐(S)‐43 and (−)‐(R)‐43, respectively.
Synthesis of β ‐Cyperone via Fungal Hydroxylation of thujone‐derived tricyclic cyclopropanes
Authors: Kutney James P. , Wagner Jürgen , Hewitt Gary M.
Published: December 2004

Synthesis of optically active sesquiterpenes with a eudesmane C‐skeleton from the chiral starting material thujone involves transformation of a tricyclic intermediate (1R,2R,4S)‐1,7‐dimethyl‐4‐(1‐methylethyl)tricyclo[4.4.0.02,4]dec‐6‐en‐8‐one (2) into the bicyclic compound β ‐cyperone (5). Hydroxylation of 2 at C(5) or C(11) permits subsequent opening of the cyclopropane ring and rearrangement to β ‐cyperone. In this publication, studies involving hydroxylation of 2 by fungal cultures are presented. The resultant products are useful intermediates in efficient synthesis of eudesmane sesquiterpenes. Of five fungi tested, Rhizopus oryzae ATCC 11145 proved most versatile. It hydroxylates at the exocyclic C(11) position in high yield (70%) and, to a lesser extent, at C(5) (5%). Enzymatic activity appears at the end of growth phase and at least 2.2 g of 2 per liter can be metabolized without significant loss of product yield. A second fungus, Cunninghamella echinulata ATCC 9244, proved most useful for hydroxylation of derivatives of 2 for the preparation of derivatives of β ‐cyperone, although product yields were low (2–20%), some derivatives were nonreactive, and hydroxylation at C(9) occurred. The relationship between precursor structure and enzyme affinity is discussed.
Nucleotides. Part XLIV. Synthesis, characterization, and biological activity of monomeric and trimeric cordycepin‐cholesterol conjugates and inhibition of HIV‐1 replication
Authors: Wasner Marita , Pfleiderer Wolfgang , Henderson Earl E. , Suhadolnik Robert J.
Published: December 2004

The antivirally active 3′‐deoxyadenylyl‐(2′–5′)‐3′‐deoxyadenylyl‐(2′–5′)‐3′‐deoxyadenosine (cordycepin trimer core) was modified at the 2′‐ or 5′‐terminus, by attachment of cholesterol via a carbonate bond (→ 15) or a succinate linker (→ 16 and 27) to improve cell permeability. The corresponding monomeric conjugates 4, 7, and 21 of cordycepin were prepared as model substances to study the applicability of the anticipated protecting groups – the monomethoxytrityl (MeOTr), the (tert‐butyl)dimethylsilyl (tbds), and the β ‐eliminating 2‐(4‐nitrophenyl)ethyl (npe) and 2‐(4‐nitrophenyl)ethoxycarbonyl (npeoc) groups – for the final deblocking steps without harming the ester bonds of the conjugate trimers. The syntheses were performed in solution using phosphoramidite chemistry. The fully protected trimer conjugates 13, 14, and 26 as well as all intermediates were characterized by elemental analyses, UV and 1H‐NMR spectra. The deblocked conjugates 15, 16, and 27 were pure according to HPLC and showed the correct compositions by mass spectra. Comparative biological studies indicated that cordycepincholesterol conjugate trimers 16 and 27 were 333‐ and 1000‐fold, respectively, more potent inhibitors of HIV‐1‐induced syncytia formation than cordycepin trimer core.
The Revised Structure of the Norditerpenoid Alkaloid Peregrine
Authors: de la Fuente Gabriel , Ruíz‐Mesía Lastenia , Rodriguez Matías L.
Published: December 2004

The structure of peregrine (1), a norditerpenoid alkaloid isolated from Delphinium peregrinum var. elongatum BOISS., was revised on the basis of the 1H‐COSY, HMQC, HMBC, and ROESY NMR spectra and of the X‐ray analysis of its parent alcohol 2. Some of the 13C‐NMR resonances of 1 and the related alkaloids peregrine alcohol (2), 14‐O‐acetylperegrine (3), bicoloridine (4), bicoloridine alcohol (5), 6‐O‐acetylbicolorine (6), bicolorine (7), and 14‐O‐acetylbicolorine (8), were also reassigned.
A Kinetic Analysis of the Reaction Catalysed by (Hydroxymethyl)bilane Synthase
Authors: Niemann Annette C. , Hädener Alfons , Matzinger Peter K.
Published: December 2004

(Hydroxymethyl)bilane synthase (HMBS) catalyses the conversion of porphobilinogen (2) into the (hydroxymethyl)bilane derivative 3, a linear tetrapyrrolic intermediate in the biosynthesis of haem, chlorophyll, and related pigments. The conversion involves the sequential formation of four intermediate covalent enzyme‐substrate complexes, before the product is released. We analysed the pre‐steady‐state kinetics of the formation of the complexes, taking advantage of their remarkable chemical stability allowing chromatographic separation. The experimental approach involved the generation of the complexes while HMBS was immobilised on an anion‐exchange column. A solution being 0.2 Km in substrate was pumped through the column during a time interval which was varied to sample the pre‐steady‐state period. Then, the enzyme and enzyme‐substrate complexes were eluted and their proportions evaluated. A computer simulation of the pre‐steady‐state time course, in combination with a χ2 fitting to the experimental data, allowed the specificity constants kcat/Km for the individual steps of the process to be derived. By repeating the analysis with variants of HMBS in which specific amino acids were replaced by others, we demonstrated that it is possible to trace the consequences of amino‐acid replacements down to the individual steps of the reaction sequence. Since the positions of the amino acids concerned in the three‐dimensional structure were known, detailed structure‐function relationships become evident in this way.
Synthesis of Carbo‐ and Heterocyclic Cycloprop[f]indenes via cycloaddition of dienes to cyclopropenes
Authors: Müller Paul , Miao Zhongshan
Published: December 2004

The heterocyclic cycloprop[f]indene 19 was synthesized via cycloaddition of diene 10 to the cyclopropene 11a and subsequent base‐induced aromatization. While 19 is isolable, although very short‐lived, the oxa analogue 18 decomposed under the conditions required for its preparation. The difluoro derivatives 14 and 15, in which the heterocyclic moiety is saturated, are accessible by the cycloaddition approach, but the corresponding dichlorides are again not isolable. Cycloprop[f]indenes carrying substituents at C(4) have been obtained via cycloaddition of 22b to 1‐bromo‐2‐chlorocyclopropene. The key step of the sequence is a double Curtius degradation of the cycloadduct 23b to the ketone 27a. While aromatization of the alcohol 27b provided the cycloprop[f]indenol 28b, the reaction failed with 27a. Attempts to convert 28b to 1,3‐dihydrocycloprop[f]indene (25) via the methanesulfonate 28d failed.
Synthesis of [Ir3Rh(CO)12] and Fluxional Behaviour of Some of Its Substituted Derivatives
Authors: Bondietti Giacomo , Laurenczy Gábor , Ros Renzo , Roulet Raymond
Published: December 2004

The redox condensation of [Ir(CO)4]–, [Ir(cod)(THF)2]+, and [Rh(cod)(THF)2]+ (cod = cycloocta‐1,5‐diene) followed by saturation with CO (1 atm) in THF afforded the first synthetic route to pure [Ir3Rh(CO)12] (1). Substitution of CO by monodentate ligands gave [Ir3Rh(CO)8(μ2‐CO)3L] (L = Br–,2; I–, 3; bicyclo[2.2.1]hept‐2‐ene, 4; PPh3, 5). Clusters 2–5 have Cs symmetry with the ligand L bound to the basal Rh‐atom in axial position. They are fluxional in solution at the NMR time scale due to two CO scrambling processes: the merry‐go‐round of basal CO's and changes of basal face. An additional process takes place in 5 above room temperature: the intramolecular migration of PPh3 from the Rh‐ to a basal Ir‐atom. Substitution of CO by polydentate ligands gave [Ir3Rh(CO)7–x(μ2‐CO)3(η4‐L)x] (L = bicyclo[2.2.1]hepta‐2,5‐diene (= norbornadiene; nbd), x = 1, 6; L = nbd, x = 2, 13; L = cod, x = 1, 7; L = cod x = 2, 15), [Ir3Rh(CO)7(μ2‐CO)3(η2‐diars)] (diars = 1,2‐phenylenebis‐(dimethylarsine); 8), [Ir3Rh(CO)7(μ2‐CO)3(η4‐L)] (L = methylenebis(diphenylphosphine), bonded to 2 basal Ir‐atom (9a) or one Ir‐ and one Rh‐atom (9b)), [Ir3Rh(CO)6(μ2‐CO)3(η4‐nbd)PPh3] (12), and [Ir3Rh(CO)6(μ2‐CO)3(μ3‐L)] (L = 1,3,5‐trithiane, 10; L = CH(PPh2)3, 11). Complexes 6–8, 9a, 10, and 11 have Cs symmetry, the others C1 symmetry. They are fluxional in solution due to CO scrambling processes involving 1, 3, or 4 metal centres as deduced from 2D‐EXSY spectra. Comparison of the activation energies of these processes with those of the isostructural Ir4 and Ir2Rh2 compounds showed that substitution of Ir by Rh in the basal face of an Ir4 compound slows the processes involving 3 or 4 metal centres (merry‐go‐round and change of basal face), but increases the rate of carbonyl rotation about an Ir‐atom.
Synthesis and reactions of 2‐(alkylthio)‐4,4‐dimenthyl‐1,3‐thiazole‐5(4H)‐thiones
Authors: Shi Junxing , Linden Anthony , Heimgartner Heinz
Published: December 2004

Six 2‐(alkylthio)‐substituted 4,4‐dimethyl‐1,3‐thiazole‐5(4H)‐thiones were synthesized according to a new method. The reactions of these compounds with allyl‐ and benzyllithium reagents, 1,3‐dipoles, and dimethyl acetylenedicarboxylate proceeded in a similar manner to 2‐alkyl‐substituted analogues, while methyllithium reacted in a different way yielding trithio‐orthoester derivatives.
New Results in the Synthesis of Styrylazulene Derivatives: Application of the ‘Anil synthesis’ to the preparation of azulenes substituted with styryl groups at the seven‐membered ring
Authors: Briquet Anne Andrée Sophie , Hansen Hans‐Jürgen
Published: December 2004

The synthesis of 4,6,8‐trimethyl‐1‐[(E)‐4‐R‐styryl]azulenes 5 (R=H, MeO, Cl) has been performed by Wittig reaction of 4,6,8‐trimethylazulene‐1‐carbaldehyde (1) and the corresponding 4‐(R‐benzyl)(triphenyl)phosphonium chlorides 4 in the presence of EtONa/EtOH in boiling toluene (see Table 1). In the same way, guaiazulene‐3‐carbaldehyde (2) as well as dihydrolactaroviolin (3) yielded with 4a the corresponding styrylazulenes 6 and 7, respectively (see Table 1). It has been found that 1 and 4b yield, in competition to the Wittig reaction, alkylation products, namely 8 and 9, respectively (cf. Scheme 1). The reaction of 4,6,8‐trimethylazulene (10) with 4b in toluene showed that azulenes can, indeed, be easily alkylated with the phosphonium salt 4b. 4,6,8‐Trimethylazulene‐2‐carbaldehyde (12) has been synthesized from the corresponding carboxylate 15 by a reduction (LiAlH4) and dehydrogenation (MnO2) sequence (see Scheme 2). The Swern oxidation of the intermediate 2‐(hydroxymethyl)azulene 16 yielded only 1,3‐dichloroazulene derivatives (cf. Scheme 2). The Wittig reaction of 12 with 4a and 4b in the presence of EtONa/EtOH in toluene yielded the expected 2‐styryl derivatives 19a and 19b, respectively (see Scheme 3). Again, the yield of 19b was reduced by a competing alkylation reaction of 19b with 4b which led to the formation of the 1‐benzylated product 20 (see Scheme 3). The ‘anil synthesis’ of guaiazulene (21) and the 4‐R‐benzanils 22 (R=H, MeO, Cl, Me2N) proceeded smoothyl under standard conditions (powered KOH in DMF) to yield the corresponding 4‐[(E)‐styryl]azulene derivatives 23 (see Table 4). In minor amounts, bis(azulen‐4‐yl) compounds of type 24 and 25 were also formed (see Table 4). The ‘anil reaction’ of 21 and 4‐NO2C6H4CH=NC6H5 (22e) in DMF yielded no corresponding styrylazulene derivative 23e. Instead, (E)‐1,2‐bis(7‐isopropyl‐1‐methylazulen‐4‐yl)ethene (27) was formed (see Scheme 4). The reaction of 4,6,8‐trimethylazulene (10) and benzanil (22a) in the presence of KOH in DMF yielded the benzanil adducts 28 to 31 (cf. Scheme 5). Their direct base‐catalyzed transformation into the corresponding styryl‐substituted azulenes could not be realized (cf. Scheme 6). However, the transformation succeeded smoothly with KOH in boiling EtOH after N‐methylation (cf. Scheme 6).