bluuebunny/crossref_metadata_2025 huggingface dataset:
Carotinoidsynthesen über Sulfone; Synthese von β‐Carotin
Authors: Fischli Albert , Mayer Hans
Published: December 2004

Sulfones, prepared from conjugated arylsulfonyl ylids and allylic halides, eliminate corresponding aryl sulfinates with formation of conjugated polyenes. Using this method β‐carotene (8) has been synthesized.
Über Pterinchemie 53. Mitteilung 1. Zur Konformation von 6‐Methyl‐ und 5,6‐Dimethyl‐5,6,7,8‐terahydropterin in wässeriger Lösung
Authors: Weber Rudolf , Viscontini Max
Published: December 2004

NMR.‐Untersuchungen an 6‐Methyl‐ und 5,6‐Dimethyltetrahydropterin in wässeriger Lösung zeigen, dass der Tetrahydropyrazinring in der Halbsessel‐Konformation vorliegt, wobei die Methylgruppe von 6‐Methyl‐tetrahydropterin aus Stabilitätsgründen praktisch ausschliesslich die äquatoriale Stellung einnimmt, während die beiden Methylgruppen von 5,6‐Dimethyl‐tetrahydropterin sich etwa zu gleichen Teilen in axialer und äquatorialer Lage befinden. Durch stark Protonierung (FSO3H) lassen sich die cis‐ und trans‐Isomeren des 5,6‐Dimethyltetrahydropterins im NMR.‐Spektrum nachweisen.
Automatic Geometry Optimization and Vibrational Analysis in External Electric Field: Ethylene
Authors: Pancíř Jiří , Zahradník Rudolf
Published: December 2004

Stationary points of the INDO energy hypersurface for various orientations of ethylene in external electric fields of the strength F=0, 2, 4, 6, 8 and 10 × 1010 V m−1 were found and their characteristics studied by the force constant matrix analysis. Energies, structural parameters, charges, Wiberg indices and dipole moments are presented. The only stable orientation of the ethylene molecule is that for which the CC bond is parallel to the field direction up to F=6 × 1010 V m−1 (orientation (a) in Fig. 1). Above this value the molecule is structurally unstable and it decomposes to the hydride anion and the C2H3+ cation. Rotational instability was found for two perpendicular orientations of the CC bond with respect to the field vector, in which the field vector was parallel and perpendicular to the molecular plane. Pseudorotations with negative eigenvalues of force constant matrices lead to the stable orientation (a). No stationary points were found when the angle between the CC bond and the field vector was between 0 and 90°. The five longest wavelength vibrational bands are presented for selected orientations and field strengths.
Delayed Fluorescence from Upper Excited Singlet States Sn (n > 1) of the Aromatic Hydrocarbons 1,2‐benzanthracene, fluoranthene, pyrene, and chrysene in methylcyclohexane
Authors: Nickel Bernhard
Published: December 2004

Delayed fluorescence (DF.) spectra of 1,2‐benzanthracene, fluoranthene, pyrene, and chrysene in methylcyclohexane were measured at −80° up to the wavenumber corresponding to the energy of two triplets. With all four compounds a weak DF. Sn → S0 from the highest state Sn accessible by triplet‐triplet annihilation (TTA) was found. Lifetimes of Sn calculated (a) from the ratio of the DF's Sn → S0 and S1 → S0 and (b) from the difference in line‐width of the 0,0‐transitions Sn,0 ← S0,0 and S1,0 ← S0,0 agree reasonably well. This indicates that population of the highest accessible excited singlet state is the dominating primary process in the excited singlet channel of TTA. There is no evidence for excimer formation being the first step in TTA. DF. spectra extend up to the energy of two triplets. With pyrene the intensity distribution in the hot‐band region of the DF. S2 → S0 suggests that in TTA the same vibrational selection rules are valid as in one‐photon absorption S2 ← S0 and that vibrational relaxation within the S2 manifold is slow compared with internal conversion S2 ↝ S1. The experimental technique is described in detail and experimental difficulties arising from impurities and photoproduct formation are discussed.
What is the ‘Solvent’ effect on the electronic spectra of a solute in a polymer matrix?
Authors: Schmidt Erika , Loeliger Hans , Zürcher René
Published: December 2004

The theory of solvent‐induced shifts of the absorption and fluorescence band spectra of a solute is well known and has been tested for a multitude of systems. However, there are only few applications to polymers. By a direct comparison of the spectral shifts in liquid solvents with those in polymers it is possible to determine the microenvironment of the solutes in polymers within the frame of this theory. Polyethylene terephthalate as fabric and film was chosen as model polymer. The spectral shifts of 15 fluorescing solutes in this polymer as well as in 10 solvents with widely differing refractive indices n and permittivities ϵ were measured and fitted to the equations given by the theory of the solvent effect. It is found that interactions with the permanent dipoles of polyethylene terephthalate may be neglected within the limits of accuracy attainable for this polymer and the chosen solutes. Dispersion forces dominate the solvent effect. The refractive indices effective at the site of the solute molecules are n = 1.66 for the fabric and n = 1.70 for the film.
Umwandlung der diastereomeren 12‐ und 6‐gliedrigen 1‐Acetyl‐2‐methyl‐1‐cycloalkanole in 1‐Äthinyl‐2‐methyl‐1‐cycloalkene
Authors: Karpf Martin , Walton David , Dreiding André S.
Published: December 2004

Conversion of the Diastereoisomeric 12‐and 6‐membered 1‐Acetyl‐2‐methyl‐1‐cycloalkanols to 1‐Ethynyl‐2‐methyl‐1‐cycloalkenes

This paper is concerned primarily with a derivation of the E‐configuration of 1‐ethynyl‐2‐methyl‐1‐cyclododecene (10), which plays a role in mechanistic considerations on a method for ring expansion by 3 carbon atoms described in apreceding paper [1]. The derivation is based on an argument using the results of the dehydration of trans‐1‐acetyl‐1‐2‐methyl‐1‐cyclododecanol (4) to 10 with phosphorus oxychloride and pyridine. That this dehydration is stereospecific can be concluded from its regiospecificity since the cis‐hydroxyketone 3 dehydrates mainly to 1‐ethynyl‐12‐methyl‐1‐cyclododecene (mixture of stereoisomers 11 and 12). An x‐ray analysis shows the indicated configurations of the two hydroxyketones 3 and 4.

The direction (anti) of the stereospecificity of the double bond introduction during the 4→10 conversion is deduced from the similarity of the behaviour of the two stereoisomeric 1‐acetyl‐2‐methyl‐1‐cyclohexanols 8 and 9 under the same conditions and from mechanistic considerations, which make it likeley that the anti‐elimination behaviour observed in the 6‐membered system has not changed over to a syn‐elimination behaviour in the 12‐membered system. The configurations of the two 6‐membered hydroxyketones 8 and 9 correspond to those of the precursor1‐ethynyl‐2‐methyl‐1‐cyclohexanols 6 and 7, which were clarified with the help of 13C‐NMR.‐spectral coupling observations.

It is of interest that the hydroxyketones 3, 4, 8 and 9 react with phosphorus oxychloride and pyridine so as to introduce both a double and a triple bond. It is probable that the double bond is introduced first, inasmuch as the triple bond is not introduced in the absence of activation of the hydroxyl group, as for instance in acetylcyclohexane. This can be used as an argument that the conversion of the acetyl to an ethynyl group in 3, 4, 8 and 9 does not affect the stereospecificity of the dehydration which introduces the ring double bond.

1‐Acetyl‐2‐methyl‐1‐cyclododecene (24), a previously isolated compound with pleasant odor, was synthesized by hydration of 10. This furnishes an argument for the E‐configuration of 24.
The stereospecific synthesis of all four stereoisomers of 2‐amino‐6‐phenoxy‐cyclohexanol,
Authors: Lier Edouard , Berthold Richard , Troxler Franz
Published: December 2004

Epoxidation of 3‐phenoxycyclohexene 5 with m‐chloro‐perbenzoic acid gave 6 and 7 in a ratio of 9:1. These two epoxides were heated with a series of amines to give the aminophenoxycyclohexanol derivatives 1 and 2 respectively; in all cases the reaction was regio‐ and stereospecific. Two methods based on the principle of neighbouring group participation were developed to synthesize the cis‐amino alcohols 3 and 4. In the first, the hydroxy group was used to introduce an amine function at the vicinal carbon atom. In the second method, the amino group served as the point of reference and the configuration of the adjacent alcohol function was inverted.
Der massenspektrometrische Zerfall isomerer Diacetamido‐cyclo‐hexane, ihrer N‐Phenäthyl‐Derivate und Bis (acetamidomethyl)cyclohexane. 32. Mitteilung über massenspektrometrische Untersuchungen,,
Authors: Süess Hans , Hesse Manfred
Published: December 2004

The Mass Spectral Decomposition of Isomeric Diacetamido‐cyclohexanes, their N‐Phenethyl‐Derivatives and Bis(acetamidomethyl)cyclohexanes

In the mass spectra of the six isomeric diacetamidocyclohexanes 2‐‐4 (cis and trans each, Scheme 2) as well as of the six isomeric bis(acetamidomethyl)cyclohexanes 6‐‐8 (cis and trans each, Scheme 5) are clear differences between the constitutional isomers, whereas cis/trans isomers show very similar spectra. The lack of stereospecific fragmentations is explained by loss of configurational integrity of the molecular ion before fragmentation.

However, the mass spectral fragmentation of epimeric diamidocyclohexanes becomes very stereospecific by the introduction of a phenethyl group on one of the nitrogen atoms: this group avoids epimerization of the molecular ion prior to fragmentation. In the N‐phenethyl derivatives 10, 11, 13 and 14 (Scheme 8) the typical fragmentations of the cis‐isomer after loss of ·C7H7 from the molecular ion are the elimination of CH2CO by formation of cyclic ions, and the loss of p‐toluenesulfonic acid or benzoic acid, respectively, with subsequent elimination of CH3CN (Scheme 9). In the trans‐isomer the typical fragmentations are the loss of the side chain bearing a tertiary nitrogen atom, and the elimination of the tosyl or benzoyl radical, respectively, with subsequent loss of CH3CONH2 (Scheme 10).
Rhodium‐Catalyzed Deuterioformylation of 3‐Methyl‐1‐pentene
Authors: Stefani Annibale , Tatone Dante , Pino Piero
Published: December 2004

3‐Methyl‐1‐pentene was deuterioformylated in the presence of rhodium‐catalyst. The extent of attack on each face of the olefin was evaluated from the diastereomeric composition of both positional isomers obtained as the products. An overall preferred attack on the si‐si face of the (S)‐enantiomer, and on the re‐re face of the (R)‐enantiomer was found.
Azimine. III. Kristallstruktur von (1E, 2Z)‐ und (1Z, 2E)‐2, 3‐Dimethyl‐1‐phthalimido‐azimin,
Authors: Moor Robert , Grieb Rita , Niggli Alfred , Hoesch Lienhard , Dreiding André S.
Published: December 2004

Azimines. III.

Teilweise vorgetragen in Bern an der Jahresversammlung der Schweizerischen Gesellschaft für Kristallographie, 7.Oktober 1977, und als Autoreferat veröffentlicht [2].

Crystal structure of (1E,2Z)‐ and (1Z,2E)‐2,3‐dimethyl‐1‐phthalimido‐azimine

Teilweise aus der Diplomarbeit von R. M., ETH Zürich 1977.

The structures of two diastereoisomeric 2,3‐dimethyl‐1‐phthalimido‐azimines, obtained by addition of phthalimido‐nitrene to (E)‐azomethane, have been determined by X‐ray analysis. The major adduct 2a forms rhombic (space group Cmc21), the minor one 2b triclinic crystals (space group Pl). The molecular structures of 2a and 2b in the crystal exhibit several interesting features: (1) The azimines 2a and 2b are true dipolar systems with a coplanar skeleton and with bond angles of about 120°. Thus both azimine N,N bonds are potentially stereogenic centers; (2) 2a and 2b differ in configuration at both of these centers: 2a has
Sterols with Cyclopropane‐Containing Side Chains: Synthesis and Acid Isomerization
Authors: Tarchini Claudio , Rohmer Michel , Djerassi Carl
Published: December 2004

To test the eventual involvement of sterols with a cyclopropane containing side chain in bio‐methylation processes, 24,25‐methanocholest‐5‐en‐3β‐ol (5) and 24,25‐methano‐26‐methylcholest‐5‐en‐3β‐ol (6) were synthesized. Together with the naturally occurring cyclopropane petrosterol (1), they were submitted to acid isomerization to provide chemical models for some of their potential metabolites.
Heterocyclic Spiro‐naphthalenones. Part III. Synthesis and reactions of some spiro [naphthalene‐1,2′‐pyrrolidin]‐2‐ones and spiro [naphthalene‐2,2′‐pyrrolidin]‐1‐ones
Authors: Berney Daniel , Schuh Karlheinz
Published: December 2004

The spironaphthalen‐2‐ones 2, 10 and 18 were prepared by N‐bromosuccinimide (NBS) oxidation of 1, 9 and 17 respectively, whereas spironaphthalen‐1‐ones 24 and 25 were obtained by treating 23 with NBS.

The stereoisomeric reduction products 29, 30 and 32 obtained from 24 and 25, gave the pentacyclic compound 33 on treatment with polyphosphoric acid.
Application de la réaction de Wittig à la synthèse de dérivés de bromoénosuloses et d'esters bromoénuroniques. Note de laboratoire
Authors: Tronchet Jean M. J. , Martin Olivier R. , Zumwald Jean‐Bernard
Published: December 2004

Use of the Wittig reaction for the synthesis of derivatives of bromoenosuloses and bromoenuronic esters

Treatment of 3‐O‐benzyl (or 3‐O‐methyl)‐1, 2‐O‐isopropylidene‐α‐D‐xylo‐pentodialdo‐1, 4‐furanoses (2 or 1) with acetylbromomethylidenetriphenylphosphorane (3), benzoylbromomethylidenetriphenylphosphorane (4) or bromoethoxycarbonylmethylidenetriphenylphosphorane (5) gave in good to excellent yields the expected enose (6‐‐11). In all cases but one (8 where some 10% of the E‐isomer was formed) the reaction led to the exclusive formation of the Z‐isomer whose configuration was established by NMR.
Photochemische Reaktionen 113. Mitteilung [1]. Zur Photospaltung konjugierter γ, δ‐Epoxyenone: UV.‐Bestrahlung von 5, 6‐Epoxy‐3,4‐didehydro‐5,6‐dihydro‐β‐jonon
Authors: Murato Kazuo , Wolf Hans Richard , Jeger Oskar
Published: December 2004

The Photoinduced Cleavage of Conjugated γ, δ‐Epoxyenones: UV.‐Irradiation of 5,6‐Epoxy‐3, 4‐didehydro‐5,6‐dihydro‐β‐ionone

On 1n, π*‐excitation (λ ≥ 347 nm) in pentane or CClF2CFCl2 (E)‐1 is isomerized to the dihydrofurane (E/Z)‐2 as well to the ethers 3 and 5. Besides these products the isomeric cyclopropane derivative (E)‐4 and the acetal 6 are obtained in methanol. The detection of 6 indicates the formation of an intermediate ketoniumylide a which may give 6 by addition of methanol. − On 1π, π*‐excitation (λ=254 nm) in acetonitrile‐d3, CClF2CFCl2 or pentane (E)‐1 yields almost exclusively (E)‐2. In methanol 6 is obtained in addition to (E/Z)‐2, but no (E)‐4 and 5 is formed.
Action du cyanure mercurique sur quelques halogénures de désoxy‐3‐trifluoroacétamido‐3‐D‐ribofurannosyle. Note de laboratoire
Authors: Tronchet par Jean M. J. , Grouiller Annie , Martin Olivier R.
Published: December 2004

Reactions of Some 3‐Deoxy‐3‐trifluoroacetamido‐D‐ribofuranosyl Halides with Mercuric Cyanide

The expected 2,5‐anhydro‐D‐allononitrile 11 was obtained when the 2‐O‐benzoyl‐3‐deoxy‐3‐trifluoroacetamido‐D‐ribofuranosyl bromide reacted with mercuric cyanide, whereas the isomeric 1,2‐O (1‐cyanoethylidene) derivative was formed from the 2‐O‐acetylated halide; no reaction occurred when the halide was 2‐O‐p‐nitrobenzoylated.
Zur Synthese sulfonierter Derivate von 4‐ und 5‐Aminoindan
Authors: Courtin Alfred
Published: December 2004

On the Synthesis of Sulfonated Derivatives of 4‐ and 5‐Aminoindan

Baking the hydrogensulfate salt of 4‐aminoindan (1) and 5‐aminoindan (2) led, respectively, to 4‐aminoindan‐7‐sulfonic acid (3) and 5‐aminoindan‐6‐sulfonic acid (4). Acid 4 was also obtained by direct sulfonation of 2. 4‐Aminoindan‐6‐sulfonic acid (5) and 6‐aminoindan‐4‐sulfonic acid (6) were prepared by sulfonation of 4‐nitroindan (7) and 5‐nitroindan (9), respectively, to 4‐nitroindan‐6‐sulfonic acid (8) and 6‐nitroindan‐4‐sulfonic acid (10), followed by a Béchamp‐reduction. Treatment of 1 with amidosulfuric acid gave 3, whereas the same reaction with 2 led to a mixture of 4 and 5‐aminoindan‐4‐sulfonic acid (11). Independent synthesis of 11 was achieved by the following sequence of reactions: sulfur dioxide treatment of the diazonium chloride derived from 4‐amino‐5‐nitrodan (13) gave 5‐nitroindan‐4‐sulfonyl chloride (14); hydrolysis to 5‐nitroindan‐4‐sulfonic acid (15), and final reduction. The 4‐aminoindan‐5‐sulfonic acid (16) was synthesized by treatment of 4‐amino‐7‐bromoindan (18) with amidosulfuric acid to give 4‐amino‐7‐bromoindan‐5‐sulfonic acid (19) followed by hydrogenolysis. Sulfonation of 4‐acetyl‐amino‐7‐bromoindan (17) with oleum followed by hydrolysis led to 7‐amino‐4‐bromoindan‐5‐sulfonic acid (20), the structure of which was confirmed by reductive dehalogenation to 5.
Synthese der Phoracantholide K, O und M
Authors: Gerlach Hans , Künzler Peter
Published: December 2004

Synthesis of Phoracantholide K, O and M

Two 14membered ring lactones 3 and 4 and a 12membered ring lactone 5 isolated from the metasternal secretion of the eucalypt longicorn Phoracantha synonyma have been synthesized as racemic mixtures by the following method. Reaction of the dilithium derivative of 5‐hexynoic acid (6) with threo‐8‐bromo‐2,4‐isopropylidenedioxyoctane (7), followed by removal of the protecting group and esterification with diazomethane gave methyl‐threo‐11, 13‐dihydroxy‐5‐tetradecy‐noate (8) (s. Scheme 2). Partial hydrogenation of the triple bond in 8 with Lindlar Pd‐catalyst, followed by saponification lead to (threo, Z)‐11, 13‐dihydroxy‐5‐tetra‐decenoic acid (10). The dihydroxy acid 10 was converted into the S‐(2‐pyridyl) thioate and cyclized in diluted benzene solution under the influence of silver ions to yield the corresponding 12‐ and 14‐membered lactones in approximately equal amounts. Isomerization of the mixture with p‐toluenesulfonic acid in methylene chloride yielded the 14‐membered lactone (cis‐11, 13–5Z)‐11‐hydroxy‐5‐tetradecen‐13‐olide almost exclusively. It proved to be identical in its properties with natural phoracantholide K (3). With 5‐hexynoic acid and 7‐tetrahydropyranyloxy‐octyl bromide or 5‐tetrahydropyranyloxy‐hexyl bromide as starting materials (±)‐phoracantholide O (4) and M (5) have been synthesized in an analogous manner.
Beiträge zur Kenntnis des chromophoren Systems der Corrine. X. Über die Reaktion von Derivaten des Cobyrinsäure‐heptamethylesters mit unterchloriger Säure
Authors: Sauer Ernst Michael , Laas Harald , Inhoffen Hans Herloff
Published: December 2004

Contributions to the Knowledge of the Corrin Chromophore, X. Reaction of Derivatives of Cobyrinic Acid Heptamethyl Ester with Hypochlorous Acid

(Cobalt)‐dicyano‐, chloro‐cyano‐, and dichloro‐cobyrinic acid heptamethylesters (1, 2 and 3), respectively, as well as their 10‐chloro derivatives 4, 5 and 6 react with hypochlorous acid. A report on the structure and some properties of the reaction products 8, 9 and 10 is given.
Transition metal complexes with bidentate ligand 2, 11‐Bis (diphenylphosphinomethyl)benzo[c]phenanthrene (1). X. Preparation and spectroscopic properties of cis‐[PtCl2 (1)] trans‐ and cis‐[PtH (PPh3) (1)] [BF4] and crystal and molecular structure of cis‐[PtCl2 (1)] · CHCl3
Authors: Bracher Gustav , Grove David M. , Venanzi Luigi M. , Bachechi Fiorella , Mura Pasquale , Zambonelli Luigi
Published: December 2004

It is shown that ligand 1, designed to span trans‐positions, under appropriate conditions also gives cis‐mononuclear complexes of platinum (II). The structure of cis‐[PtCl2 (1)] (2) has been determined by single‐crystal X‐ray diffraction. The major distortion from square planar coordination is the P‐Pt‐P angle of 104.8°. Values of valence angles within the bidentate ligand indicate that this part of the molecule is very strained. Two phenyl groups, one on each phosphorus, lie almost parallel to each other separated by ca. 3.2–3.3 Å. The 1H‐NMR. data for this compound show that the π‐phenyl interactions observed in the solid state occur also in solution. The preparation and NMR.‐spectroscopic properties of trans‐ and cis‐[PtH(PPh3) (1)] [BF4] are reported.
Synthesis of Verrucarin A and 3α‐Hydroxyverrucarin A from Verrucarol and Diacetoxyscripenol (Anguidine). 39th Communication on Verrucarins and Roridins
Authors: Mohr Peter , Tori Motoo , Grossen Peter , Herold Peter , Tamm Christoph
Published: December 2004

The title compounds have been synthesized starting from verrucarol and diacetoxyscripenol (anguidine), (E, Z)‐muconic half ester and a derivative of verrucarinic acid. The latter has been prepared in optically active form from dimethyl 3‐methylglutarate.
Photoelectrochemistry with Colloidal Semiconductors; Laser Studies of Halide Oxidation in Colloidal Dispersions of TiO2 and α‐Fe2O3
Authors: Moser Jacques , Grätzel Michael
Published: December 2004

Aqueous sols of TiO2 (anatase, particle radius 25 Å) were excited with (347.1 nm)‐laser light and the reaction of valence‐band holes with halide ions (X = I−, Br−, Cl−) was investigated. Hole transfer takes place within the duration of the (10 ns)‐laser pulse and results in the formation of anion radicals according to the sequence:magnified image

The quantum yield of X increases in the order Cl < Br < I, attaining 0.8 for I at pH 1. It is affected by pH, halide concentration and the presence of a protective agent for the sol.

RuO2 deposited onto TiO2 enhances markedly Cl and Br ‐formation, but has no effect on the yield of I.

Laser‐photolysis investigation of halide oxidation were also carried out with colloidal Fe2O3 (particle radius 600 Å). For I2−formation, the quantum yield exceeds 0.9 indicating almost quantitative hole scavenging by iodide.
Structure of New 2‐Oxo‐2,8‐dihydro‐[l,2,4]oxadiazolo‐[2,3‐a]pyrimidinecarbamates
Authors: Muller Jean‐Claude , Rarouz Henri , Daly John , Schönholzer Peter
Published: December 2004

The structure of new 2‐oxo‐2,8‐dihydro‐[l,2,4]oxadiazolo‐[2,3‐a]pyrimidine‐carbamates 1 was established by correlating the IR. and NMR. data with these of analogous compounds. A X‐ray crystallographic analysis of 1c gave an unequivocal proof of structural assignment.
Directional Preferences of Ether O‐Atoms Towards Alkali and Alkaline Earth Cations
Authors: Chakrabarti Pinakpani , Dunitz Jack D.
Published: December 2004

An analysis of the environments of alkali and alkaline earth cations complexed to ethers has been made with the Cambridge Structural Database. The cations invariably lie close to the bisecting plane through the O‐atoms. The larger cations show an apparent preference to approach the ether group along a tetrahedral lone pair direction, whereas Li+ cations tend to be found along the COC bisector, i.e., along the trigonal lone pair direction. These observations are discussed in relation to recent theoretical and experimental findings.
Über die Enantiomerentrennung durch Verteilung zwischen flüssigen Phasen. 4. Mitteilung. Enantioselektivität der diastereoisomeren Weinsäure‐dimenthylester gegenüber α‐Aminoalkohol‐Salzen
Authors: Prelog Vladimir , Dumić Miljenko
Published: December 2004

Separation of Enantiomers by Partition between Liquid Phases. Enantioselectivity of Diastereoisomeric Dimenthyl Tartarates towards α‐Aminoalcohol Salts

The enantioselectivity of the easily obtainable diastereoisomeric dimenthyl tartarates I and II towards the salts of a series of α‐aminoalcohols 1‐10 was investigated by partition between aqueous and lipophilic phase. The measured enantiomer distribution constants Q (=KA/KB) confirm the previously observed configurational relationships between the lipophilic tartarates and the preferentially extracted enantiomer of the hydrophilic ammonium slat. However, the (R,R)‐ester I is appreciably more selective than its (S,S)‐diastereoisomer II or other previously investigated esters. The tartarates I‐III transport norephedrin salts through bulk lipophilic membranes with enantioselectivity comparable to that observed in partition experiments. The most enantioselective ester I can be used as an efficient mobile phase for preparative separation of norephedrine enantiomers by flash partition chromatography.
An Fe57Mössbauer Study of Selected Binary and Ternary Vanadium Sulfides
Authors: Bensch Wolfgang , Schlögl Robert , Amberger Eberhard
Published: December 2004

Mössbauer data recorded at room temperature and 78 K for several binary and two new ternary vanadium sulfides are presented. The results are discussed in comparison with the structures and magnetic susceptibility measurements. A change in the spin state of the Fe‐atoms from the Fe2+ high‐spin state to the low‐spin state is observed in the binary vanadium sulfides. This change is due to a shortening of the crystallographic c‐axis which is nearly parallel to short metal‐metal distances. In one ternary thallium vanadium sulfide the Fe is in the unusual trivalent low‐spin state at room temperature.
Syntheses of Cyclopropyl Silyl Ketones
Authors: Scheller Markus E. , Frei Bruno
Published: December 2004

The synthesis of the cyclopropyl silyl ketones 1–4 is described. The trimethylsilyl ketone 1 was prepared from geraniol ((E)‐5) in ca. 10% overall yield by cyclopropanation leading to 6, CrO3 oxidation to the aldehyde 8, reaction of the latter with trimethylsilyl anion to 14A+B, and CrO3 oxidation to 1. Also for the (t‐butyl)dimethylsilyl ketones 2–4, an efficient four‐step synthesis with overall yields of 48%, 85%, and 13%, respectively, was elaborated, starting from the allylic alcohols (E)‐5, and 23. The method of preparation involves as the key step a Wittig rearrangement of the silylallyl ethers ((E/Z)‐20, 24) to the silyl alcohols ((E/Z)‐21, 25), subsequent cyclopropanation (19A + B, 22A + B, 26), and oxidation to the cyclopropyl silyl ketones 2–4.
Metal complexes with macrocyclic ligands. Part XXII. Synthesis two of bis‐tetraaza‐macrocycles and study of the structures, electrochemistry, VIS and EPR spectra of their binuclear Cu2+ and Ni2+ complexes
Authors: Schneider Renè , Riesen Andreas , Kaden Thomas A.
Published: December 2004

The two bis‐macrocycles 4 and 5 in which the tetraaza units are separated by a chain of different length, have been synthesized using 1,4,7‐tritosyl‐1,4,7,11‐tetraazacyclotetradecane as starting compound and bifunctional alkylating agents. The bis‐macrocycles give binuclear complexes with Ni2+ and Cu2+, the properties of which have been studied to obtain information about the interaction of the two subunits as a function of the distance. The VIS spectra of the Ni2+ and Cu2+ complexes indicate that both metal ions are in a square‐planar geometry as expected from the results of the analogous complexes with 1,4,7,11‐tetraazacyclotetradecane 7. Cyclic voltammetry and differential pulse polarography of the binuclear Ni2+complexes in CH3CN show a single two‐electron step for ligand 5, whereas two distinct one‐electron redox processes can be observed for ligand 4, indicating that the two metal ions interact with each other when the chain length is shorter. Similarly, the EPR studies of frozen solutions of the binuclear Cu2+ complexes clearly show that a magnetic dipolar interaction between the two paramagnetic centers exists, and that the strength of it depends upon the length of the bridge. Finally, from the X‐ray structures of the binuclear Ni2+ complexes with 4 and 5, it is seen that the two rings are kept apart as far as possible, the distances between the two metal ions determined in the solid correlate well with the observations in solution.
C45‐ und C50‐Carotinoide. 3. Mitteilung. Synthese von (S)‐Trisanhydrobacterioruberin
Authors: Wolf Jean‐Pierre , Pfander Hanspeter
Published: December 2004

C45‐and C50‐Carotenoids: Synthesis of (S)‐Trisanhydrobacterioruberin

The Synthesis of (S)‐trisanhydrobacterioruberin ((S)‐1) is reported.
Chiral metals? A chiral substrate for organic conductors and superconductors
Authors: Wallis John D. , Karrer Andreas , Dunitz Jack D.
Published: December 2004

Chiral metals are so far practically unknown. The synthesis of a chiral substrate for possible organic conductors and superconductors is described.
1H‐ and 13C‐NMR Investigation of Nonafulvenes
Authors: Otter Albin , Sabbioni Gabriele , Neuenschwander Markus , Kellerhals Hans Peter
Published: December 2004

1H‐ and 13C‐NMR spectra of a series of nonafulvenes 1 have been investigated. Most nonafulvenes are olefinic molecules with alternating bond lengths, their nine‐membered ring deviating strongly from planarity. The 10‐monosubstituted nonafulvenes contain 2 sterically different ring segments with a nearly planar (E)‐diene system consisting of C(7), C(8), C(9), C(10), and R. Substituents R are influencing C(9) > C(7) > C(5). In symmetrically substituted nonafulvenes a fast process equilibrating olefinic conformers is operating so that pairs of ring protons and ring C‐atoms are equivalent and only average substituent effects are observed for C(9) > C(7,2). 1H‐ and 13C‐NMR chemical shifts are not significantly influenced by changes of solvent or temperature. On the other hand, new 13C‐ and 1H‐NMR experiments completing previous investigations by Hafner and Tappe confirm that NMR spectra of 10,10‐bis (dialkylamino)nonafulvenes are strongly dependent on solvent polarity and temperature. At ambient temperature and in unpolar solvents, nonplanar conformers are predominant, their spectral data fitting into the series of other nonafulvenes. At low temperature and/or in polar solvents, dipolar conformers are favoured which are characterised by charge separation and a planarised (but not necessarily completely planar) nine‐membered ring with negative excess charge. The spectroscopic behaviour of nonafulvenes is reasonably explained by a qualitative scheme (Fig. 7) which is based on a model proposed by Boche for nonafulvenolates.
Conformation‐Odor Relationships in Norlabdane Oxides
Authors: Ohloff Günther , Vial Christian , Demole Edouard , Enggist Paul , Giersch Wolfgang , Jégou Elise , Caruso Andrew J. , Polonsky Judith , Lederer Edgar
Published: December 2004

Conformational factors have been found responsible for the dramatic change in odor between (−)‐deoxyambreinolide (12) and its (+)‐epi derivative 13. The presumably molecular event during the receptor interaction has been simulated by the diastereoisomeric 11‐methyl‐ambrox derivatives 3 and 5 as model compounds.
Additionsreaktion von 1,3‐Thiazol‐5(4H)‐thionen und inaminen; Bildung von Thioamiden und Thioketonen
Authors: Jenny Christjohannes , Heimgartner Heinz
Published: December 2004

Addition Reaction of 1,3‐Thiazole‐5(4H)‐thiones and Ynamines; Formation of Thioamides and Thioketones

Ynamines and 1,3‐thiazole‐5(4H)‐thiones of type 1 undergo an addition reaction on heating in toluene yielding mainly α,β‐unsaturated 2‐(4,5‐dihydro‐1,3‐thiazol‐5‐yliden)thioamides of type 7 (Scheme 2 and Table). In some cases, 1‐diethylamino‐1‐(4,5‐dihydro‐1,3‐thiazol‐5‐yliden)‐2‐alkanethiones 8 have been isolated as minor products. In analogy to other reactions of ynamines with CO and CS bonds, a [2 + 2] cycloaddition to thiete intermediates, followed by an electrocyclic ring opening is suggested as reaction mechanism.
Synthesis of (E)‐1‐Propenyl Ketones from Carboxylic Esters and Carboxamides by Use of Mixed Organolithium‐Magnesium Reagents. Synthesis of α‐Damascone, β‐Damascone, and β‐Damascenone
Authors: Fehr Charles , Galindo José
Published: December 2004

The novel reagents formed by combination of allylmagnesium chloride and a strong non‐nucleophilic lithium base (LiNR2) convert non‐ or slowly enolizable carboxylic esters or carboxamides into 2‐propenyl ketones which are protected from further reaction by their in situ conversion into enolates. This modified Grignard reaction is applied to efficient syntheses of α‐damascone, β‐damascone, β‐damascenone, and various other (E)‐1‐propenyl ketones.
Drug‐induced modifications of the immune response part 94‐(Arylamino)‐2,5‐dihydro‐2‐oxo‐N‐(trans‐2‐phenylcycolopropyl)furan‐3‐carboxamides as Novel Antiallergic Compounds
Authors: Georgiev Vassil St. , Mack Robert A. , Walter David J. , Radov Lesley A. , Baer Jane E.
Published: December 2004

The synthesis and antiallergic activity of a series of 4‐(arylamino)‐2,5‐dihydro‐2‐oxo‐N‐(trans‐2‐phenyl‐cyclopropyl)furan‐3‐carboxamides 10 are described. Treatment of N‐substituted 2‐amino‐4,5‐dihydro‐4‐oxofuran‐3‐carboxylic acids 9 with chlorooxobis(2‐oxo‐1,3‐oxazolidin‐3‐yl)phosphorus (2) and an appropriate aromatic amine in the presence of Et3N, resulted in a novel 3(2H)‐furanone‐→2(5H)‐furanone rearrangement that led to the facile preparation of the new amides 10. The latter exerted a potent antiallergic activity when tested in the dermal vascular permeability and active anaphylaxis assays in rats. The most active compound 10b inhibited the action of serotonin, histamine, and bradykinin by 94, 92, and 100%, respectively, when administered intraperitoneally to rats at doses of 100 mg/kg. The present series of 10 represents a novel class of antiallergic agents.
On Negative Birefringence in Water‐in‐Oil Microemulsions
Authors: Hilfiker Rolf , Eicke Hans‐Friedrich , Hammerich Holger
Published: December 2004

The occurrence of a negative birefringence in water‐in‐oil (W/O) microemulsions has been substantiated and analyzed. The analysis is based on the well‐established aqueous nanodroplet model of W/O microemulsions. In the particularly investigated water/sodium bis(2‐ethylhexyl)sulfosuccinate (AOT)/aliphatic oil systems, the AOT monolayer exhibits a negative induced intrinsic birefringence, which is brought about by the pronounced polarizability of the alkyl moiety of the AOT molecule approximately perpendicular to the direction of its permanent dipolement.
Two New Antifungal Naphthoxirene Derivatives and their Glucosides from Sesamum angolense WELW
Authors: Potterat Olivier , Stoeckli‐Evans Helen , Msonthi Jerome D. , Hostettmann Kurt
Published: December 2004

Two novel naphthoxirene derivatives 1 and 2 their glucosides 3 and 4 have been isolated from the root bark of Sesamum angolense Welw. (Pedaliaceae) by preparative liquid chromatography. The structure of 1 was established by X‐ray diffraction analysis. The identities of the other naphthcxirenes were deduced by spectroscopic (IR, UV, 1H‐NMR, 13C‐NMR, EI‐MS, DCI‐MS) and chemical methods (oxidation, acid and enzymatic hydrolysis). Compounds 1–3 exhibited antifungal activity. Naphthoxirene 1 was, in addition, cytotoxic to human colon carcinoma cells.
N6‐(Carbamoylmethyl)‐2′‐deoxyadenosine, a rare DNA Constituent: Phosphoramidite Synthesis and Properties of Palindromic Dodecanucleotides
Authors: Seela Frank , Herdering Wilhelm , Kehne Andreas
Published: December 2004

N6‐(Carbamoylmethyl)‐2′‐deoxyadenosine (1), a modified nucleoside occurring in bacteriophage Mu, was synthesized by two different routes. Glycinamide was introdued by nucleophilic displacement of(2,4,6,‐triisopro‐pylphenyl)sulfonyloxy or ethylsulfinyl groups at C(6) of the purine moiety. Compound 1 was converted into the protected phosphoramidite 6b and employed in solid‐phase synthesis of the self‐complementary oligonucleotides 7–14. Replacement of 2′‐deoxyadenosine by 1 led to a strong decrease of the Tm values of the oligomers d(A‐T)6 (7) and d(A‐T‐G‐A‐A‐G‐C‐T‐T‐C‐A‐T)(10), respectively. As the oligemer 10 contains the recognition site d(A‐A‐G‐C‐T‐T) of the endodeoxyribonuclease Hind III, it was subjected to sequence‐specific hydrolysis experiments. Replacement of the first or second Ad by 1 prevented enzymatic phosphodiester hydrolysis (results with 11 and 12). In contrast, slow hydrolysis was observed if the less bulky N6‐methyl‐2′‐deoxyadenosine replaced the second Ad residue (results with 14).
Synthesis of Chiral 12‐Phenyl(2H)dodecanoic Acids: Useful metabolic probes for the biosynthesis of 1‐alkenes from fatty acids
Authors: Görgen Günther , Boland Wilhelm , Preiss Ute , Simon Helmut
Published: December 2004

The synthesis of chiral 12‐phenyi(2H)dodecanoic acids as metabolic probes for the evaluation of the stereo‐chemical course of the biosynthesis of 1‐alkerses from fatty acids in plants and insects is described. The diastereoisomeric (2R, 3R)‐ or (2S, 3S)‐12‐phenyl(2,3−2H2)dodecanoic acids 11 are obtained in high chemical and optical yield (>97% e.e.) from the readily available (E)‐12‐phenyl(2,3‐2H2)dodec‐2‐enoic acid (10) or (E)‐12‐phenyldodec‐2‐enoic acid (10a) by microbial reduction with wet packed cells of Clostridium tyrobutyricum in either 2H2O or H2O buffer. (2R)‐ and (2S)‐12‐phenyl(2−2H)dodecanoic acids 9 (>97% e.e.) are accessible from the allylic alcohol 6 via Sharpless epoxidation with (+)‐L‐ or (−)‐D‐diethyl tartrate, Synthetic routes to the (E)‐ and (Z)‐11‐phenyl(1−2H) undec‐1‐enes 16 and 16a as reference compounds are also included.
Verschiedenartige Addukte von Ketonen, Diazocyaniden sowie Nitrosobenzol an (Methylidenamino)phosphene
Authors: Ried Walter , Fulde Maria , Bats Jan W.
Published: December 2004

Various Adducts from Ketones, Diazocyanides, and Nitrosobenzene with (Methylidenamino)phosphines

(Methylidenamino)phosphine 1a reacts with activated ketones to 2,7‐dioxa‐5‐aza‐1λ5‐phosphabicyclo‐[3.2.0]heptanes 2a, b and with nitrosobenzene to l, 3,5,2λ5‐oxadiazaphosphole 3a. The reaction of 1b with nitrosobenzene and diethyl mesoxalate yields 2,7‐dioxa‐3,5‐diaza‐1λ5‐phosphabicyclo[3.2.0]heptane 4. With the cyano group of diazocyanides, 1a reacts to the adducts 5a–d. The structure of 5a is proven by an X‐ray diffraction analysis.
Energy‐Minimized Structures and Calculated and Experimental Isomer distributions in the hexaamine‐cobalt(III) system [Co(L)2]3+ with the chiral facially‐coordinating triamine (l = butane‐1,2,4‐triamine)
Authors: Comba Peter , Maeder Marcel , Zipper Luc
Published: December 2004

Butane‐ 1,2,4‐triamine (trab) is the smallest tridentate aliphatic unsubstituted chiral triamine. With optically pure trab, there are three, with racemic trab five isomers of [Co(trab)2]3+, One of the five isomers is centrosymmetrical, the others are chiral. For one of the isomers, there are four possible conformations (all combinations of chair and skew boat conformations for the chelate six ring of each ligand), for the others there exist only three independent conformers. All sixteen independent structures have been calculated by strain‐energy minimization. The calculated isomer distribution, based on total strain energies corrected with statistical entropy contributions (21%:16%:16%:4%:43%, and 40%:30%:30%, for racemic and optically pure trab, respectively) are in excellent agreement with the experimental data based on HPLC and 13C‐NMR analyses of equilibrium solutions of the hexaamine‐Co(III) compounds prepared by oxygenation of aqueous solutions in presence of activated charcoal. The results are also briefly discussed in relation to possible stereoselectivity upon complexation of optically pure trab and a racemic chiral ligand to a transition‐metal center.
An Unexpected Asymmetric Reduction of 4‐(1‐Nitro‐2‐oxocyclododecyl)butan‐2‐one. Determination of the absolute configuration of (‒)‐15‐hexadecanolide
Authors: Stanchev Stephan , Hesse Manfred
Published: December 2004

Reduction of the carbonyl group in the side chain of 4‐(1‐nitro‐2‐oxocyclododecyl)butan‐2‐one (3) with organoboron complexes are influenced by the chiral center, in 4‐position with respect to the carbonyl C‐atom, to which the NO2 group is attached, a rare type for an asymmetric reduction. Independent of the (R)‐ or (S)‐configuration of the Alpine‐Hydride, (+)‐3 is reduced only to the (15S)‐nitrolactone (+)‐5 and, after subsequent transformations, to (+)‐(‐S)‐15‐hexadecanolide ((+)‐1), enantiomer of the naturally occurring (−)‐1.
Synthesis of Polyaza Macrocyclic Ligands Incorporating Pyridine Units
Authors: Hosseini Mir Wais , Comarmond Jacques , Lehn Jean‐Marie
Published: December 2004

The synthesis of nine macrocyclic polyamines 2‐10 containing pyridine units is described. These compounds are 22‐ (9), 24‐ (2‐4,6,8,10), or 26‐ (5, 7) membered hexaaza (2,3,9,10) or octaaza (4–7) macrocycles in which one to four pyridine units are incorporated. Compounds 3,4,9, and 10 are homoditopic ligands, whereas 2 and 5 are heteroditopic and 6−8 multitopic receptors. Compounds 2‐10 are potential ligands for metal cations as well as, in their protonated forms, for anions. Protonated macrocycles 2−10 are also potential catalysts for the hydrolysis of nucleotides and polyphosphates.
Bretonin A and Isobretonin A, Unique Glycerol Derivatives Isolated from a Demosponge of Brittany Waters
Authors: Guella Graziano , Mancini Ines , Pietra Francesco
Published: December 2004

It is shown that an unidentified marine demosponge of Brittany contains two unique lipids consisting of glycerol etherified by a C12 trienic linear alcohol and esterified by 4‐hydroxybenzoic acid. The latter is attached to the secondary position of glycerol in bretonin A (= 3‐[((4E, 6E, 8E)‐dodeca‐4,6,8‐trienyl)oxy]‐2‐(4‐hydroxy‐benzoyl)propan‐1‐ol; 1a), and to the other primary position of glycerol in isobretonin A ( = (+)‐3‐[((4E, 6E, 8E)‐dodeca‐4,6,8‐trienyl)oxy]‐1‐(4‐hydroxybenzoyl)propan‐2‐ol; (+)‐2). The structures are based on NMR and MS data, including the ones of the acetylation product (−)‐1b of 1a.
Structural Aspects of the Enantioselectivity of Tartrates with α‐Amino‐alcohol Salts part. I. Crystal structures of eleven tartaric‐acid diesters
Authors: Egli Martin , Dobler Max
Published: December 2004

Enantioselective host‐guest complexes of α‐amino‐alcohol salts with chiral tartaric‐acid esters can not be crystallised up to now. To study structural aspects of their enantioselectivity, crystal structures of the components were determined. The structures of eleven diesters with myrtanol, borneol, menthol, neomenthol, and cis‐4‐(tert‐butyl)cyclohexanol in different configurations showed a remarkable rigidity of the tartaric‐acid conformation, partly because of intramolecular H‐bonding between OH and C=O groups. The conformation of the tartaric‐acid part in these diesters is the same as the one observed in optically active tartaric acid (torsion angle OCCOH ca. 0°), The binding site for guest molecules is a parallelogram formed by two hydroxy and two carbonyl O‐atoms, all lying on the same side of a mean molecular plane. There is one exception: the dimenthyl ester, which is the most enantioselective with a norephedrine guest, has one of the ester groups turned (torsion angle OCCOH ca. 180°), forming a triangle of O‐atoms and moving the bulky menthyl group to the vicinity of the binding site.
Enantioselective Optode Membranes with Enantiomer Selectivity for (R)‐ and (S)‐l‐Phenylethylammonium Ions
Authors: Holý Petr , Morf Werner E. , Seller Kurt , Simon Wilhelm , Vigneron Jean‐Pierre
Published: December 2004

The recently developed general principle of ion‐selective optode membranes, based on conventional ionophores, was employed to design a new approach to the determination of enantiomeric excess. Highly lipophilic chiral crown derivatives, exhibiting a high selectivity for a chiral ammonium guest cation, are combined with a H+‐selective chromoionophore in a plasticized PVC membrane. The enantiomer recognition process is translated by this sensor with an optical transduction into a signal easily measured by a conventional spectrophotometer, and enantiomeric excess can be determined without the need for polarized light. Characteristics and a theoretical description of these new optode membranes are given.
2‐Aza‐l, 3‐dienes. Partie 6. Observation d′un effet ‘tert‐amino’ dans le traitement acide de (pyrrolidin‐l‐yl)‐azadienes
Authors: Legroux Didier , Brotn Jacques , Fleury Jean Pierre
Published: December 2004

‘tert‐Amino Effect’ on Acidic Treatment of (Pyrrolidin‐l‐yl)azadienes

The behaviour of 4‐morpholino‐ and 4‐(pyrrolidin‐l‐yl)‐2‐aza‐1. 3‐diene‐l, l‐dicarbonitriles 3, and 4 and 10, respectively, in acidic medium is described. The former gives with HBr/AcOH 3‐bromopyrazine‐2‐carbonitrile 6. On the other hand, pyrrolidin‐1‐yl derivatives 4 and 10 furnish, by a [1, 5]‐H shift, pyrrolo[l, 2]pyrazine structures 5 and 11, respectively.
Synthesis of IH‐Cyclopropal[g]quinoline via Trapping of an ortho‐Quinodimethane
Authors: Müller Paul , Schaller Jean‐Pierre
Published: December 2004

1H‐Cyclopropa[g]quinoline (3‐aza‐lH‐cyclopropa[b]naphthalene; 17) was synthesized via interception of the heterocyclic ortho ‐quinodimethane 15 with l‐bromo‐2‐chlorocyclopropene, followed by aromatization of the adduct 16 with t‐BuOK.
Rh(II)‐Catalyzed Isomerizations of Cyclopropenes Evidence for Rh(II)‐Complexed Vinylcarbene Intermediates
Authors: Müller Paul , Pautex Nicole , Doyle Michael P. , Bagheri Vahid
Published: December 2004

The thermocatalytic rearrangements of cyclopropenes 1‐4 have been investigated in the presence of Rh(IT) perfiuorobutyrate. 1, 2, 3‐Triphenylcyclopropene (1a) undergoes rearrangement lo diphenylindene 5a or, with alkoxycyclopropene derivatives, to α, β‐unsaturated ketone 6. Furan formation occurs with 2, 3‐diphenylcyclo‐propenecarboxylate 2, but the diethyl counterpart 3 rearranges to dienoate 8. 2‐Alkylcyclopropenecarboxylates 4 afforded (E)‐methylidenecyclopentane derivatives 9 as the only isolable product in yields of ca. 35 %. A mechanism involving regio‐ and stereospecific cyclopropene ring opening to a Rh‐complexed vinylcarbene and insertion of the latter into the CH bond to give 9 is proposed. An analogous mechanism should account for the rearrangement products of 1 to 3.
Isolation and Characterization of s̀‐Adducts upon Attempted Vicarious Nucleophilic Substitution with Cationic Arene‐Iron Complexes
Authors: Müller Paul , Bernardinelli Gérald , Motallebi Shahrokh
Published: December 2004

Reaction of the carbanions derived from chloromethyl phenyl sulfone or 1 ‐chloroethyl phenyl sulfone with the cationic [Fe(arene)Cp] complexes 8 or 9 produced isolable c‐adducts 10‐12. Attempted base induced elimination of the s̀‐adducts, which would have led to products of vicarious nucleophilic substitution (VNS reaction), failed. Similarly, no VNS products were obtained, when the (arene)tricarbonylchromium complexes 4 were reacted with the anion of chloromethyl phenyl sulfone.
Synthesis of All Four Stereoisomers of (E)‐Vitamin KT (Phylloquinone), Analysis of Their Diastereoisomeric and Enantiomeric Purities and Determination of Their Biopotencies
Authors: Schmida Rudolf , Antoulas Syméon , Rüttimann August , Schmid Max , Vecchi Max , Weiserb Harald
Published: December 2004

All four stereoisomers of (E)‐vitamin Kb i. e. (21E, 7R, 111R)‐l (= 1a), (21E, 71 R, l11S)‐1 (= 1b), (21E, 71 S, 111S) 1 ( = 1c), and (21E, 71S, 111R)‐l ( = Id), have been synthesized in a state of high chemical and stereoisomeric purity. The synthesis of stereoisomers lb‐d relied on the use of the optically active Cf1* and C*10‐building blocks (R)‐ or (S)‐4‐(benzyloxy)‐3‐methylbutanal ((R)‐ or (S)‐2) and (R)‐ or (S)‐citronellal ((R)‐ or (S)‐3) which had been secured by the Rh1‐catalyzed allylamine‐to‐enamine isomerization technology. For the synthesis of the natural (E)‐vitamin‐K1 stereoisomer 1a, a new route starting from natural phylol was developed, based on an O‐alkylation/rearrangement procedure. A HPLC method was developed which separates with remarkable efficiency all four stereoisomers of (E)‐ as well as three out of the four stereoisomers of (Z)‐vitamin K1 on optically active poly(trityl methacrylate) as the chiral stationary phase supported on Nucleosil. By this method, the stereoisomeric content of the stereoisomers 1b‐d synthesized was shown to be in the range of 96‐98 %, while the natural isomer 1a was configurationally uniform. The biological activity of the four (E)‐vitamin‐K1 stereoisomers was determined by means of the curative prothrombin time test with vitamin‐K‐depleted chicks. A high precision of the results was obtained with the recently introduced up‐and‐down organization of the test and the statistical evaluation according to an estimation procedure. With the natural (E)‐vitamin‐K1 stereoisomer 1a as standard (set at 1. 0), activities of 0. 93, 1. 19, and 0. 99 were found for stereoisomers 1b, 1c, and 1d, respectively. Within the confidence limits, these activity ratios can be regarded as identical, A very similar efficacy was obtained by comparison of (E, all‐rac )‐vitamin K1 ((21E, RS, 11′ RS)‐1; equimolar mixture of the four stereoisomers 1a‐d) with the natural (E)‐vitamin‐K1 stereoisomer 1a). A synergistic effect was not detectable, as was the case with the eight α‐tocopheryl‐acetate stereoisomers.