bluuebunny/crossref_metadata_2025 huggingface dataset:
Desoxy‐nitrozucker 14. Mitteilung 1‐C‐Nitroglycale. Herstellung und Umsetzung mit einigen Stickstoff‐Nucleophilen
Authors: Baumberger Franz , Beer Dieter , Christen Markus , Prewo Roland , Vasella Andrea
Published: December 2004

1‐C‐Nitroglycals. Preparation and Reaction with Some Nitrogen Nucleophiles

Acetylation of the 1‐deoxy‐1‐nitromannopyranoses 2 and 6 was accompagnied by spontanous β‐elimination to give the 1‐C‐nitroglucals 3 and 7, respectively, while acetylation of the gluco‐ and galacto‐configurated 1‐deoxy‐1‐nitropyranoses 8 and 14 gave the acetates 9 and 15, respectively (Scheme 1). The acetylation of the ribo‐ and arabino‐configurated 1‐deoxy‐1‐nitrofuranoses 19 and 21 also occurred without β‐elimination to give the acetates 20 and 22, respectively (Scheme 2). Mild base treatment of the previously described O‐acetylnitro‐β‐D‐glucose 4, the O‐acetylnitro‐β‐D‐pyranoses 9 and 15, and the O‐acetylnitro‐β‐D‐furanoses 17, 20, and 22 gave the 1‐C‐nitroglycals 3, 10, 16, 18 and 23, respectively (Scheme 1 and 2). The previously obtained 1‐C‐nitroglucal 3 was deacetylated by treatment with MeOH in the presence of KCN or sodium m‐nitrophenolate to give the free nitroglucal 5. Deacetylation of the benzylidene protected 1‐C‐nitroglucal 10 (MeOH, NaOMe) gave the 4,6‐O‐benzylidene‐1‐C‐nitroglucal 11 and traces of the 2‐O‐methyl‐1‐C‐nitromannoses 12 and 13. The UV, IR, 1H‐NMR and 13C‐NMR spectra of the 1‐C‐nitroglycals are discussed. In solution, the 1‐C‐nitroglycals 1, 5, 7, 10, 11, and 16 adopt approximately a 4H5− and 3 a flattened 4H5 conformation. The structure of 5 was established by X‐ray analysis. In the solid state, 5 adopts a sofa conformation, which is stabilized by an intramolecular H‐bond. The β‐addition of NH3 to the 1‐C‐nitroglucals 7 and 10 was followed by an O→ N acetyl migration to give exclusively anomeric pairs of the N‐acetyl‐1‐nitromannosamine derivatives 24/25 and 26/27, respectively (Scheme 3). The β‐addition of methylamine, octadecylamine, and tryptamine to the 1‐C‐nitroglucal 11 also stereoelectronically controlled and gave the crystalline N‐alkyl‐1‐nitromannosamines 28, 29, and 30, respectively. The stereoelectronically controlled β‐addition of NH3 to the 1‐C‐nitrogalactal 16, followed by acetylation, yielded exclusively the talosamine derivative 31, while the reversible β‐addition of azide ions to 16 gave the anomeric 2‐azido‐1‐nitrogalactoses 32 and 33. The β‐addition of azide ions to the 1‐C‐nitroglucal 1 led to the 2‐azido‐1‐nitromannose 34. In the presence of excess formaldehyde, this addition was followed by a Henry reaction. Chromatography of the crude product was accompagnied by solvolytic removal of the NO2 group to give the 3‐azidomannoheptulose 35 in high yields (Scheme 4).
Synthese von (Methylthio)penam‐Derivaten durch Keten‐Addition an 4,5‐Dihydro‐5‐(methylthio)‐1,3‐thiazole
Authors: Jenny Christjohannes , Prewo Roland , Bieri Jost H. , Heimgartner Heinz
Published: December 2004

Synthesis of (Methylthio)penam Derivatives via Keten Addition onto 4,5‐Dihydro‐5‐(methylthio)‐1,3‐thiazoles

The 4,5‐dihydro‐5‐(methylthio)‐2‐phenyl‐1,3‐thiazoles 3a and 3b, easily prepared from the corresponding 1,3‐thiazol‐5(4H)‐thiones and MeLi, react with dichloroacetyl chloride (5a) and acidoacetyl chloride (5b) in the presence of Et3N to give (methylthio)penam derivatives 6 (Table 1). The reaction mechanism is either a [2 + 2] cycloaddition of in situ generated ketene or a two‐step reaction (Scheme 2). The structure of 6f has been confirmed by X‐ray crystallography (Fig. 2). The relative configuration of 6a‐e follow from comparison of their 1H‐NMR spectra with those of 6f (Fig. 1). The 6‐azidopenams 6d and 6f have been reduced to aminopenams 8a and 8b, respectively. Acylation of 8a with phenacetyl chloride yields 9 (Scheme 4).
Preparation of Enantiomerically Pure β‐Silylcarboxyl Derivatives by Asymmetric 1,4‐Addition to N‐Enoyl‐sultams. Preliminary Communication
Authors: Oppolzer Wolfgang , Mills Robert J. , Pachinger Werner , Stevenson Thomas
Published: December 2004

EtAlCl2‐promoted additions of organocopper reagents to camphor‐derived, conjugated N‐enoyl‐sultams gave saturated and olefinic β‐silylcarboxyl derivatives with high diastereodifferentiation. Nondestructive removal of the chiral auxiliary followed by oxidative Si‐C bond cleavage furnished enantiomerically pure acetate‐derived aldols and propionate‐derived ‘anti’ ‐aldols (via silyl‐directed α‐methylation).
Struktur und Reaktivität von Xanthocorrinoiden. 4. Mitteilung. Hydroxylierung an C(15) des Corrin‐Chromophors bei der Reaktion von Cyanocob(III)alamin mit Udenfriend‐Reagenz
Authors: Holze Gerhard , Gossauer Albert , Ernst Ludger
Published: December 2004

Structure and Reactivity of Xanthocorrinoids. C(15) Hydroxylation of the Corrin Chromophore on Reaction of Cyanocob(III)alamin with Udenfriend's Reagent

Hydroxy‐corrinoid 4 represents a new type of corrin derivatives whose chromophore is identical with that of products formed on bacterial degradation of cyanocob(III)alamin (1). In vitro, 4 is obtained by O2 oxidation of 1 in the presence of ascorbic acid and cupric ions.
Thermal Methyl‐Group Transfer between Methylcobalt(III) Corrinates and Cobalt(II) Corrinates. Equilibration Experiments with Heptamethyl Cobyrinates and Cobalamins
Authors: Kräutler Bernhard , Hughes Mark , Caderas Christian
Published: December 2004

Separate neutral aqueous solutions of either (a) methylcob(III)alamin (2) and (heptamethyl cob(II)yrinate) perchlorate (3) or of b) cob(II)alamin ( = vitamin B12r; (4) and [Coβ‐methyl(heptamethyl cob(III)yrinate)] perchlorate (5) equilibrated thermally at r.t. according to 2 + 3 ⇄ 4 + 5. The corresponding equilibrium constant Ke was determined (Ke = 0.63 ± 0.15). This equilibration experiment indicates that the coordination of the nucleotide function in methylcob(II)alamin (2) hardly affects the thermodynamics of the CoC bond homolysis in aqeous solution when compared to nucleotide‐free methylcorrinoids such as 5.
Singlet‐Oxygen Ene Reactions of (E)‐4‐Propyl[1,1,‐2H3]oct‐4‐ene. Short Communication
Authors: Rautenstrauch Valentin , Thommen Walter , Schulte‐Elte Karl H.
Published: December 2004

Rose bengal‐sensitized photooxygenation of 4‐propyl‐4‐octene (1) in MeOH/Me2CHOH 1:1 (v/v) and MeOH/H2O 95:5 followed by reduction gave (E)‐4‐propyl‐5‐octen‐4‐ol (4), its (Z)‐isomer 5, (E)‐5‐propyl‐5‐octen‐4‐ol (6), and its (Z)‐isomer 7. Analogously, (E)‐4‐propyl[1,1,1‐2H3]oct‐4‐ene (2) gave (E)‐4‐propyl[1,1,1‐2H3]oct‐5‐en‐4‐ol (14), its (Z)‐isomer 15, (E)‐5‐[3′,3′,3′‐2H3]propyl‐5‐octen‐4‐ol (16), its (Z)‐isomer 17, and the corresponding [8,8,8‐2H3]‐isomers 18 and 19 (see Scheme 1). The proportions of 4–7 were carefully determined by GC between 10% and 85% conversion of 1 and were constant within this range. The labeled substrate 2 was photooxygenated in two high‐conversion experiments, and after reduction, the ratios 16/18 and 17/19 were determined by NMR. Isotope effects in 2 were neglected and the proportions of corresponding products from 1 and 2 assumed to be similar (% 4 ≈︁ % 14; % 5 ≈︁ % 15; % 6 ≈︁ % (16 + 18): % 7 ≈︁ % (17 + 19)). Combination of these proportions with the ratios 16/18 and 17/19 led to an estimate of the proportions of hydroperoxides formed from 2. Accordingly, singlet oxygen ene additions at the disubstituted side of 2 are preferred (ca. 90%). The previously studied trisubstituted olefins 20–25 exhibited the same preference, but had both CH3 and higher alkyl substituents on the double bond. In these substrates, CH3 groups syn to the lone alkyl or CH3 group appear to be more reactive than CH2 groups at that site beyond a statistical bias.
Die Synthese von 6,7‐Dihydro‐2H‐pyrimido[6, 1‐a]isochinolin‐4(3H)‐onen und analogen Verbindungen und deren Wirkung als Blutpättchenaggregationshemmer
Authors: Kienzle Frank , Bounameaux Yves , Minder Rudolf E. , Muggli Reto
Published: December 2004

Synthesis of 6,7‐Dihydro‐2H‐pyrimido[6,1‐a]isoquinolin‐4(3H)‐ones and Analogous Compounds and their Activity as Blood‐Platelet Inhibitors

The synthesis of 6,7‐dihydro‐2H‐pyrimido[6,1‐a]isoquinolin‐4(3H)‐ones and of analogous compounds is described. These compounds are powerful phosphodiesterase inhibitors and, therefore, inhibit blood‐platelet aggregation independent of the agonist. They exhibit, too, cardiac activities. However, there is evidence for selective action. A structure‐activity relationship for platelet‐aggregation inhibitors is discussed.
Chlorine Dioxide as an Electron‐Transfer Oxidant of Olefins. Preliminary Communication
Authors: Rav‐Acha Chaim , Choshen (Goldstein) Ehud , Sarel Shalom
Published: December 2004

The kinetics and product studies of oxidation of eight olefins 1‐8 by ClO2 in H2O in the pH range 3‐7 are described. The reaction is faster as the pH decreases. At pH < 4, ClO2 reacts equimolarly with olefins to yield isomeric mixtures of chlorohydrines and 1,2‐dioxygenated products, following the equation: magnified image The order of reactivity is: (E)‐stilbene > indene > β‐methylstyrene > acenaphthylene > α‐methylstyrene > styrene > cyclohexene > allylbenzene. A multi‐stage radical‐cation mechanism is proposed, in which an initial reversible protonation:

is followed by an electron‐transfer stage (rate‐determining): magnified image The cation‐radical thus produced, adds rapidly an additional ClO2 to form dioxygenated products. The chlorohydrines most likely arise from HClO additions to the olefinic double bonds, which, in turn, generate from dismutation of 2 HClO2 into HClO + H+ + ClO.
Butanolide und Butenolide durch intramolekulare En‐Reaktion bei der Thermolyse von Propargyl‐propiolaten
Authors: Bilinski Vanda , Karpf Martin , Dreiding André S.
Published: December 2004

Butanolides and Butenolides by Intramolecular Ene‐Reaction during Thermolysis of Propargyl Propiolates

Gas‐phase flow thermolysis of 2‐butynyl propynoate (1) and 2‐propynyl 2‐butynoate (2) at 550° afforded 3‐ethynyl‐2‐methyl‐2‐buten‐4‐olide (4, 85%) and 2‐ethynyl‐3‐methyl‐2‐buten‐4‐olide (5, 80%), respectively. Their formation presumably entails an ene reaction between the methylacetylenic and the acetylenic functions of the diyne esters 1 and 2 to give the two methyliden‐vinyliden‐butanolides 10 and 11 as intermediates, followed by a [1,5]‐H shift to 4 and 5. At 400–450°, the gas phase flow thermolysis of 1 and 2 led to the dimers 16 (77%) and 17 (6%), respectively. These products resulted from the Diels‐Alder dimerization of the above mentioned intermediates 10 and 11. The regioselectivity of this dimerization is determined by a ‘head‐to‐head’ approach, with the double bond conjugated to the carbonyl group acting as the dienophile in both cases. The low yield of 17 from 2 is probably due to a further Diels‐Alder reaction of the dimer 17 with its precursor 11, yielding a trimer 18 (8% isolated). This process is not possible when starting with 1, which explains the higher yield of 16. The gas phase flow thermolysis of 2‐butynyl 2‐butynoate (3) at 550° afforded a mixture of four isomeric products, namely the two monocyclic ethynyl‐butenolides 6 and 7 and the two bicyclic vinyl‐butenolides 8 and 9. The formations of 6–9 are also rationalizable by initial ene‐reactions, in this case two alternative ones, each involving one of the two CH3 groups of 3. This leads to two alkylidene‐vinylidene‐butenolides, namely 12 and 13. A [1,5]‐H shift converts 12 into 6 and 13 into 7. A competing alternative [1,5]‐H shift transforms both 12 and 13 to the triene 14, which electrocyclizes to the cyclohexadiene 15. The latter undergoes two alternative [1,5]‐H shifts to yield 8 and 9.
Intermolecular [4 + 2]‐Cycloadditions of Nitroalkenes with Cyclic Olefins. Transformations of Cyclic Nitronates
Authors: Denmark Scott E. , Cramer Christopher J. , Sternberg Jeffrey A.
Published: December 2004

Nitrocyclohexene undergoes facile SnCl4‐induced, [4 + 2]‐cycloadditions with simple cycloalkenes to produce nitronates. The nitronates can be transformed sterospecifically into a number of other functional groups (alcohol, ketone, oxime, amine) by hydrolytic, reductive, and oxidative processes. The mechanism of the [4 + 2]‐cycloaddition is believed to involve formation of a zwitterionic intermediate which can collapse via competing pathways to form the observed products. 1,3‐Dipolar cycloadditions of the nitronates are described.
Kombinierte NOE‐ und Entkopplungsexperimente zur selektiven H‐NMR‐Detektion: Anwendung auf ein stereochemisches Problem
Authors: Bigler Peter
Published: December 2004

Combined NOE and Decoupling Experiments for the Selective H‐NMR Detection: Application to a Stereochemical Problem

The successful solution of complex stereochemical problems by NMR methods often requires scalar (J) and dipolar (NOE) data. A modern method, improved with respect to sensitivity and selectivity, which yields both scalar and dipolar informations is proposed, and an application to configurational analysis is demonstrated. The method is based on NOE effects for the detection of selected protons and homonuclear decoupling for improved resolution.
Metal complexes with macrocyclic ligands. Part XXV. One‐step synthesis of mono‐N‐substituted azamacrocycles with a carboxylic group in the side‐chain and their complexes with Cu2+ and Ni2+
Authors: Studer Martin , Kaden Thomas A.
Published: December 2004

Mono‐N‐substituted azamacrocycles 2–7, containing a carboxyalkyl or carboxyaryl side‐chain, are obtained by reacting a five‐fold excess of the macrocycle with 1 equiv. of a suitable halogenocarboxylic acid in alkaline aqueous EtOH. For halogenocarboxylic acids, which easily lactonize under alkaline conditions, a variant with the corresponding ester or nitrile as alkylating agent is also described. The salient point of this synthesis lies in the use of an excess of the macrocycle over the alkylating agent, thus reducing the amount of polyalkylation to a minimum, and in the easy separation of the excess of unreacted educt from the aminocarboxylic acid. These new ligands form Ni2+ and Cu2+ complexes, the spectral properties of which have been studied. In the case of the Cu2+ complexes with ligand 2, 3, and 6, a pH‐dependent color change is observed. This is explained with an equilibrium between a species, in which the carboxylate group is bound to the metal, and one, in which it is protonated and non‐coordinated. In the case of the Ni2+ complexes with the same ligands, only the species with a coordinated carboxylate was observed. In the Cu2+ and Ni2+ complexes with ligands 4 and 5, however, the carboxylate group does not coordinate at all, because of the length or the special structure of the chain.
Norbornanes. Part 18. Inductive Charge Dispersal in the Solvolyses of 4‐ and 5‐Substituted 2‐Norbornyl p‐Toluenesulfonates
Authors: Fuso Francesco , Grob Cyril A. , Sawlewicz Pawel , Yao Guo Wei
Published: December 2004

The solvolysis rates and products of 4‐ and 5‐exo‐substituted 2‐exo‐ and 2‐endo‐norbornyl tosylates 9 and 10, respectively, are reported. The logarithms of the rate constants (log k) correlate linearly with the inductive constants σ for the substituents. A comparison of the reaction constants p1 for the 4‐, 5‐, 6‐, and 7‐substituted 2‐exo‐ and 2‐endo‐tosylates 9, 10, 1, and 2 respectively, indicates that inductivity is higher for 2‐exo‐ionization than for 2‐endo‐ionization in all series. This observation is attributed to the more favorable alignment of neighbouring C‐atoms for dorsal participation in exo‐ionization, especially, in the case of C(6).
Molecular Anion Binding and Substrate Photooxidation in Visible Light by 2,7‐Diazapyrenium Cations
Authors: Blacker A. John , Jazwinski Jaroslaw , Lehn Jean‐Marie
Published: December 2004

The 2,7‐diazapyrenium group (DAP2+) combines the features of pyrene, of methylviologen, and of nucleicacid intercalators and may thus present a variety of interesting properties. The cations 1 and 2 and the bis‐diazapyrenium species 3 have been synthesized and shown to bind molecular anions like aromatic polycarboxylates, giving rise to pronounced shifts of 1H‐NMR signals, modifications of UV/VIS absorption spectra, and quenching of fluorescence. The complexes formed probably have a face‐to‐face structure, and their stability constants are remarkably high, in particular for the bis‐diazapyrenium cation 3 which is susceptible to form intercalative chelate complexes such as 9(log Ks ≈ 3 for 1, up to ca. 7 or more for 3a). Neutral molecules like adenine are also bound, but much less strongly. Visible‐light irradiation of Me2DAP2+ (1) in presence of various electron donors, such as EDTA, gives the reduced species Me2DAP+ wich has been characterized by UV/VIS and ESR spectroscopy. The results indicate that Me2DAP2+ (1) functions as a methylviologen analogue, photoactive in visible light. Thus 2,7‐diazapyrenium cations are attractive subunits for incorporation into macropolycyclic structures to give photo‐ and electroactive receptor molecules.
Norbornanes. Part 19. The Inductive Model for Norbornyl Cation Formation
Authors: Altmann‐Schaffner Eva , Grob Cyril A.
Published: December 2004

Two CH3 groups at C(6) of 2‐exo‐ (10a) and 2‐endo‐norbornyl p‐toluenesulfonate 11a lower their solvolysis rates in 80% EtOH by factors of 28 and 16, respectively. A spirocyclopropyl group including C(6), as in 21a and 22a, reduces the rate of exo‐ and endo‐ionization by factors of 250 and 8, respectively. The geminally dimethyl‐substituted tosylates 10a and 11a yield the 2‐exo‐alcohol 10b, whereas the spirocyclopropyl‐substituted tosylates 21a and 22a furnish rearranged 3‐brendanol 23. These findings are readily rationalized by the inductive model, according to which norbornyl cation formation is controlled by the inductive effect of dorsal substituents.
Two Unusual Trimers of Diketene
Authors: Ernest Ivan , Fritz Hans , Rihs Grety
Published: December 2004

Formation of two unknown, tricyclic trimers of diketene, 3 and 4, was observed in diketene solutions containing (CH3)3SiCl/NaI or TsOH.
Enantionselektive Synthese des L‐Threonins
Authors: Soukup Milan , Wipf Beat , Hochuli Erich , Leuenberger Hans G. W.
Published: December 2004

An Enantionselective Synthesis of L‐Threonine

An enantioselective synthesis of L‐threonine (1) is described. Racemic ethyl 2‐acetamido‐3‐oxobutyrate (6) was synthesized from ethyl acetoacetate (2) [4][5] and then transformed to the epimeric optically active alcohols 7a and 7b by microbiological reduction with Saccharomyces rouxii. The Mixture 7a/7b could be converted to 1 by slightly modified, known Methods in a yield of ca. 52% with respect to 7a/7b.
Elektrochemische Oxidation von (S)‐Äpfelsäure‐Derivaten: ein Weg zu enantiomerenreinen alkylierten Malonaldehydsäure‐estern
Authors: Renaud Philippe , Hürzeler Marianne , Seebach Dieter
Published: December 2004

Electrochemical Oxidation of (S)‐Malic‐Acid Derivatives: a Route to Enantiomerically Pure Alkylmalonaldehydic Esters

The 3,3‐dialkymalic‐acid diesters, prepared by the previously described diastereoselective alkylations through dilithium alkoxide enolates, are saponified to the monoesters containing a free α‐hydroxycarboxylic‐acid moiety(Scheme 3). The monoesters are subjected to electrochemical oxidative decarboxylation in MeOH. If the intermediate monoacids are purified, the malonaldehydic esters (2‐formy1‐2‐alkylcaroxylates) Obtained by this procedure are enantiomerically pure; they have the same structural features, i.e. two enantiotopic functionalized branches on the (persubstituted) stereogenic center, as the well known 3‐hydroxy‐2‐methylpropanoic acid (‘Roche acid’) which was employed frequently as a starting material for the preparation of either enantiomer of various target molecules.
Synthese eines Nickel(II)‐B,C,D‐hexadehydrocorrinats durch (A→D)‐Cyclisierung
Authors: Montforts Franz‐Peter , Bats Jan W.
Published: December 2004

Synthesis of a Nickel(II) B,C,D‐Hexadehydrocorrinate by (A→D)‐Ring Closure

The B,C,D‐hexadehydrocorrin of type 10 fills a gap in the corrin family whose members can occur at different oxidation levels. We report here on the synthesis of a correspondingly protected secocorrin 23 and its convenient cyclization to 10
Antimykotisch wirksame Imidazolyl‐alkene: Synthese und Röntgenstrukturanalyse von Omoconazol
Authors: Thiele Kurt , Zirngibl Ludwig , Pfenninger Max H. , Egli Martin , Dobler Max
Published: December 2004

Antimycotic Imidazolyl‐alkenes: Synthesis and X‐Ray Crystal Structure of Omoconazol

The synthesis of omoconazol 4 from 2′,4′‐dichloro‐α‐(1H‐imidazol‐1‐yl)propiophenon (5) and 1‐bromo‐2‐(4‐chlorophenoxy)ethane (6) is described. Omoconazol, C20H17Cl3N2O2, crystallises in the monoclinic space group P21/n, a = 14.329, b = 8.703, c = 16.791 Å, β = 105.75°. The crystal structure showed that omoconazol has the (Z)‐configuration, in accordance with previous NMR results.
Copper(II) Triflate, a New Reagent for Mild Dehydration of Alcohols: Synthetic Usefulness and Mechanistic Insight
Authors: Laali Khosrow , Gerzina Robert J. , Flajnik Christine M. , Geric Cynthia M. , Dombroski Ann Marie
Published: December 2004

The effectiveness of copper(II) triflate (copper(II) trifluoromethanesulfonate) as a new dehydrating reagent for a variety of alcohols has been demonstrated. Based on several control experiments, a possible mechanism is suggested.
Verapliquinones: Novel Diprenylquinones from an Aplidium sp. (Ascidiacea) of Ile‐Verte Waters, Brittany
Authors: Guella Graziano , Mancini Ines , Pietra Francesco
Published: December 2004

An Aplidium sp. (Ascidiacea), collected in French Atlantic waters near the Ile Verte, is shown to contain verapliquinone B (2) and verapliquinone D (6) as the first examples of linear diprenylquinones of the neryl type, besides their respective isomers 1 and 5 of the geranyl type.
Syntheses of (+)‐ and (–)‐Methyl 8‐Epinonactate and (+)‐ and (–)‐Methyl Nonactate
Authors: Warm Aleksander , Vogel Pierre
Published: December 2004

In four synthetic steps, (+)‐ and (–)‐methyl 8‐epinonactate ((+)‐ and (–)−4) have been derived from (+)‐ and (–)‐7‐oxabicyclo[2.2.1]heptan‐2‐one ((+)‐ and (–)−9), respectively. The (+)‐ and (–)‐methyl nonactate ((+)‐ and (–)−3) were obtained from (+)‐ and (–)−4, respectively, by Mitsunobu displacement reactions. Optical resolution of (±)−9 via chromatographic separation of the corresponding N‐methyl‐S‐alkyl‐S‐phenylsulfoximides 24 and 25 yielded the starting materials (+)‐ and (–)−9, respectively.
Photolactonisierung: Ein neuer synthetischer Zugang zu Makroliden
Authors: Quinkert Gerhard , Billhardt Uta‐Maria , Jakob Harald , Fischer Gerd , Glenneberg Jürgen , Nagler Peter , Autze Volker , Heim Nana , Wacker Manfred , Schwalbe Thomas , Kurth Yvonne , Bats Jan W. , Dürner Gerd , Zimmermann Gottfried , Kessler Horst
Published: December 2004

Photolactonization: A Novel Synthetic Entry to Macrolides

o‐Quinol acetates, hydroxyalkylated at C(6), are easily accessible from simple phenols by Wessely acetoxylation (preferentially catalyzed by BF3). On UV irradiation (in the presence of an appropriate tertiary amine), they are smoothly converted to macrocyclic lactones. Subtle conditions have been elaborated to lead to high overall yields, and the scope of the conversion of phenols to macrolides has been elucidated.
Field‐Desorption Mass Spectra of Fern Phloroglucinols Containing Three to Six Ring Constituents
Authors: Richter Wilhelm J. , Raschdorf F. , v. Euw Josef , Reichstein Tadeus , Widén Carl‐Johan
Published: December 2004

It has been previously shown that the structural analysis of the title compounds by electron‐impact ionization (EI)mass spectrometry is complicated by extensive, if not complete, thermal rottlerone‐type rearrangement and/or fragmentation reactions. The use of a ‘softer’ ionization technique such as field desorption (FD) is, therefore, required in order that these compounds may be characterized in terms of their molecular size and composition. In this report, the FD mass spectra of typical representatives of this class of compounds are described along with the attempted suppression of undesirable thermal reactions by the optimization of the emitter temperatures.
On the Photochemistry of 12,13‐Didehydrosqualene
Authors: McWhorter William W. , Jaun Bernhard
Published: December 2004

The photochemical formation of bicyclooctenes b from 12,13‐didehydrosqualene (1) upon irradiation at wavelengths longer than 290 nm is reported. The same photoreaction is also observed with trienes 7 and 8 which like 1 have a remote double bond two C‐atoms removed from the triene system. A configurational assignment for bicyclooctene 10 obtained from 8 and a mechanism for the observed photochemical reaction are proposed.
Diels‐Alder‐Reaktionen von 2,4‐Bis{[(tert‐butyl)dimethylsilyl]oxy}‐3‐aza‐1,3‐pentadien mit Heterodienophilen
Authors: Ried Walter , Reiher Uwe , Jan W. Bats
Published: December 2004

Diels‐Alder Reactions of 2,4‐Bis{[(tert‐Butyl)dimethylsilyl]oxy}‐3‐aza‐‐1,3‐pentadien with Heterodienophiles

The 2,4‐bis{[(tert‐butyl)dimethylsilyl]oxy}‐3‐aza‐1,3‐pentadien(2) reacts via the Diels‐Alder adducts 3, 6a‐c, and 8a, b, which cannot be isolated, giving the triazines 4, 7a‐c, and the oxadiazines 9a, b. The hydrolysis of 4 in MeOH affords the N‐acetyl‐acetamid derivative 5. The formula of 9a is proven by an X‐ray‐structure analysis.
Novel Synthesis of Agaritine, a 4‐Hydrazinobenzyl‐Alcohol Derivative Occurring in Agaricaceae
Authors: Datta Subir , Hoesch Lienhard
Published: December 2004

The 4‐hydrazinobenzyl alcohol (3 was prepared (58%)) by diiobutylaluminiumhydride reduction of methyl 4‐hydrazinobenzoate (4), whereas LiA1H4 or LiBh4 reduction of4 proceeded further to yield (via intermediate 3) (4‐tolyl)hydrazine (5). The alcohol 3 was stable under O2‐free conditions and exhibited no tendency to eliminate H2O, neither thermally nor with H+ catalysis. Oxidation of 3 with SeO2 yielded 4‐(hydroxymethyl)benzine‐diazonium ion (8), identified by its azo coupling product 9 with 2‐naphthol. Condensation of 3 with 1‐benzyl 5‐Hydrogen N‐(benzyloxycarbonyl)‐L‐glutamate (10) in presence of dicyclohexylcarbodiimide afforded 81% of N2‐(benzyloxycarbonyl)‐L‐ glutamic acid 1‐(benzyl‐ester) 5‐{2‐[4‐(hydroxymethyl)phenyl]hydrazide} (11) which upon controlled hydrogenolysis (quinoline‐sulfur‐poisoned Pd/C catalyst) gave 82% of L‐Glutamic acid 5‐{2‐[4‐(hydroxymethyl)phenyl] hydrazide} (1), i. e. agaritine, a metabolite of Agaricus bisporus. Without poisoning of the catalyst, hydrogenolysis of (11) yielded L‐glutamic acid 5‐[2‐(4‐tolyl)hydrazide] (12).
Nucleotides. Part XXVII Bis[2‐(p‐nitrophenyl)ethyl] Phosphorochloridate, a New Versatile Phosphorylating Agent in Nucleotide Chemistry
Authors: Himmelsbach Frank , Charubala Ramamurthy , Pfleiderer Wolfgang
Published: December 2004

A new, versatile phosphorylating agent, bis[2‐(p‐nitrophenyl)ethyl] phosphorochloridate (3), has been prepared and is used for 3′‐ and/or 5′‐phosphorylations of nucleosides. The resulting bis[2‐(p‐nitrophenyl)ethyl] phosphotriesters are versatile synthons in oligonucleotide synthesis leading finally to 3′‐ and/or 5′‐terminated monophosphates in excellent yields.
Einfache Umwandlung von(–)‐(R)‐3‐Hydroxybuttersäure in das (+)‐(S)‐Enantiomere und dessen Lacton(‒)‐(S)‐4‐Methyloxetan‐2‐on
Authors: Griesbeck Axel , Seebach Dieter
Published: December 2004

Simple Conversion of (R)‐3‐Hydroxybutanoic Acid to the (S)‐Enantiomer and its Lactone (–)‐(S)‐4‐Methylixetan‐2‐one

Condensation of (R)‐3‐hydroxybutanoic acid (1) with ethyl orthoacetate gives a 2‐ethoxy‐substituted (1,3)dioxanone 2 which is thermally labile: at ca. 100°, two competing processes commence, one leading to ethyl (R)‐3‐acetoxybutanoate (3), the other one ‐ with complete inversion of configuration ‐ to the (S)‐4‐methylixetan‐2‐one (4) and ethyl acetate. These can be readily separated by fractional distillation. Thus, enantiomerically pure (S)‐3‐hydroxybutanoic acid (ent‐1) and l‐2‐alkyl‐3‐hydroxybutanoic‐acid derivatives (such as 6 and 8) become available from the biopolymer PHB, the precursor to the acid 1.
Diasteroselektive Hydroxyalkylierungen in 1‐Stellung von Tetrahydroisochinolinen und Synthese von Aporphin‐, Protoberberin‐ und Phthalid‐Alkaloider
Authors: Seebach Dieter , Isabelle M. P. Huber , Max A. Syfrig
Published: December 2004

Diastereoselective Hydroxyalkylations in Position 1 of Tetrahydroisoquinolines and Synthesis of Aporphine, Protoberberine, and Pathalide Alkaloids

Unsubstituted and 6,7‐dialkoxy‐N‐pivaloyl‐tetrahydroisoquinolines 1–3 are converted to 1‐bromomagnesium derivatives by sequential treatment with t‐BuLi (−75°/THF) and MBr2.OEt2. Addition of the metalated tetrahydroisoquinolines to aliphatic or aromatic aldehydes occurs with relative topicity ul (Scheme 2). The 1‐hydroxyalkylated 2‐pivaloyl‐tetrahydroisoquinolines a of u‐configuration thus obtained (14 examples) can be converted to free aminoalcohols c of either l‐or u‐configuration (9 examples; Scheme 3). The depivaloylation with retention (→ u‐c) is best achieved by heating in EtOH/KOH, the conversion to 1‐aminoalcohols l‐c by treatment with CF3COOH/(CF3CO)2O (→ l,‐pivalates l‐b), followed by alkaline saponification or by LiAlH4 reduction of the esters. The configuration of the products is assigned by 1H‐NMR spectroscopy, by X‐ray crystal structure analysis, by chemical correlation, and by comparison of the chemical properties of the l‐ and the u‐isomers. The diastereoselective hydroxybenzylation of the tetrahydroisoquinoline is used for short syntheses of ushinsunine/oliveroline (Scheme 4), β‐hydrastine, and ophiocarpine/epiopliocarpine (Scheme 6; aporphine, phthalide, and protoberberine alkaloids, respectively).
Synthese von 4‐Benzylthio‐ und 4‐(Arylthio)‐1,3‐oxazol‐5(2H)‐onen
Authors: Wipf Peter , Prewo Roland , Jost H. Bieri , Heimgartner Heinz , Nastopoulos Vassilios , Germain Gabriel
Published: December 2004

Synthesis of 4‐(Benzylthio)‐and 4‐(Arylthio)‐1,3‐oxazole‐5(2H)‐ones

Following a known procedure, 4‐(benzylthio)‐1,3‐oxazol‐5(2H)‐one (4a) was synthesized starting from sodium cyanodithioformate (1) and cyclohexanone (Scheme 1). The structure of the intermediate 4‐(benzylthio)‐1,3‐thiazol‐5(2H)‐one (3a) was established by X‐ray crystallography. An alternative route was developed for the synthesis of 4‐(arylthio)‐1,3‐oxazol‐5(2H)‐ones which are not accessible by the former reaction. Treatment of ethyl cyanoformate (5) with a thiophenol in the presence of catalytic amounts of Et2NH and TiCl4, followed by addition of a ketone and BF3.Et2O in a one‐pot‐reaction, gave 4f–i in low‐to‐fair yields (Scheme 3). Both synthetic pathways‐complementary as for benzyl–S and aryl‐S derivatives–seem to be limited with respect to variation of substituents of the ketone.
Neue Aromadendran‐Derivate aus Tolu‐Balsam
Authors: Friedel Horst Dieter , Matusch Rudolf
Published: December 2004

New Aromadendrane Derivatives from Tolu Balsam

Five new aromadendrane derivatives were isolated from tolu balsam by HPLC and their structures elucidated by NMR spectroscopy.
Determination of the Quantum Yield of Intersystem Crossing of Rose Bengal
Authors: Murasecco‐Suardi Patricia , Gassmann Ernst , Braun André M. , Oliveros Esther
Published: December 2004

The quantum yield of intersystem crossing (Φisc) of a sensitizer is related to the quantum yield of singlet‐oxygen production (Φ(1O2)) by the efficiency of the energy transfer (φet) and is an important parameter in the evaluation of potential applications of sensitized photo‐oxidations. Using two different laser photolysis techniques, the energy‐transfer method and the partial saturation method, Φisc of rose bengal has been determined in MeOH and in aqueous solutions. The results confirm that with Φisc(H2O) = 1.05(± 0.06) and Φisc(MeOH)=0.90(±0.08), the generally assumed relation Φisc · φet = Φ(1O2), with φet = 1, cannot be maintained any longer (Φ(1O2, H2O) = 0.75 and Φ(1O2, MeOH) = 0.76). During these experiments, a second intermediate has been observed which is produced from the triplet state of rose bengal and, stabilized in a anionic micellar solution, has been shown to be the radical cation of the sensitizer. The efficiency of the electron transfer has been evaluated from transient absorption and bleaching recordings, and it seems conclusive to attribute the results to the difference between Φisc and Φ(1O2).
Horeau's Coupling of Enantiomers Revisited. The Reversible Coupling of Enantiomers to Form Diastereoisomers in Kinetically Labile Metal Complexes
Authors: Marty Werner , Pasquier Maurice L. , Gampp Harald
Published: December 2004

Pairs of enantiomeric molecules (ℜ︁,𝔖) of a substrate of unknown, but incomplete enantiomeric purity may be coupled to each other through labile coordination to a metal center M. This results in the formation of an equilibrium mixture of diastereoisomeric complexes, viz. meso‐LnMℜ︁𝔖(=m) and a pair of enantiomers LnMℜ︁ℜ︁ and LnM𝔖𝔖(= e), where L is an achiral auxiliary ligand. General expressions are presented for determining the ratio of enantiomers [ℜ︁]0/[𝔖]0 from experimental parameters, which may be obtained from NMR measurements. Effects of diastereoselectivity are specifically considered. Limiting cases (nearly pure or nearly racemic substrates, very high or no diastereoselectivity, very large or no excess of free substrate) are discussed. The cases of additional diastereoisomerism owing to different coordination geometries and of the formation of complexes with more than two substrate molecules per metal center are also investigated. The results presented can not only be used for determining the enantiomeric excess but also for designing optimal strategies for the successive resolution of partly enriched samples.
Regioselective Electrophilic Additions of Bicyclo[2.2.n]alk‐2‐enes Controlled by Remote Epoxide Functions
Authors: Claret François , Carrupt Pierre‐Alain , Vogel Pierre
Published: December 2004

The electrophilic additions of 2‐nitrobenzenesulfenyl chloride to (1RS,2SR,4RS)‐spiro[bicyclo[2.2.1]hept‐5‐ene‐2,2′‐oxirane] (12) and (1RS,2SR,4RS)‐spiro[bicyclo[2.2.2]oct‐5‐ene‐2,2′‐oxirane] (14) were not regioselective under condition of kinetic control. However, good regioselectivity was observed for the addition of 2‐nitro‐benzenesulfenyl chloride to (1RS,2RS,4RS)‐spiro[bicyclo[2.2.1]hept‐5‐ene‐2,2′‐oxirane] (13), giving (1RS,2SR,4SR,5RS,6RS)‐6‐exo‐(2‐nitrophenylthio)spiro[bicyclo[2.2.1]heptane‐2.2′‐oxirane]‐5‐endo‐yl chloride (24) and for the exo addition to (1RS,2RS.4RS)‐spiro[bicyclo[2.2.2]oct05‐ene‐2,2′‐oxirane] (15), giving preferntially (1RS,2SR,4SR,5RS,6 RS)‐6‐exo‐(2‐nitrophenylthio) spiro[bicyxlo[2.2.2]octane‐2,2′‐oxirane]‐5‐endo‐yl chloride (30). The facial selectivity (electrophilic exo vs. endo attack on the bucyclic alkene) depended on the relative configuration of the spiroepoxide ring in the bicyclo[2.2.2]octenes 14 and 15. The exo‐epoxide 14 was attacked preferentially (6:1) on the endo face by sulfenyl whereas exo attack was preferred (7:2) in the case of the endo‐epoxide 15. No products resulting from transannular ring expansion of the spiro‐epoxide moieties could be detected.
Isolierung von 10′‐Apo‐β‐carotin‐10′‐ol und (3R)‐10′‐Apo‐β‐carotin‐3,10′‐diol (Galloxanthin) aus Rosenblüten. 5. Mitteilung über Rosenfarbstoffe
Authors: Märki‐Fischer Edith , Eugster Conrad Hans
Published: December 2004

Isolation of 10′‐Apo‐β‐carotene‐10′‐ol and (3R)‐10′‐Apo‐β‐carotene‐3,10′‐diol (Galloxanthin) from Rose Flowers

The novel (all‐E)‐10′‐apol‐β‐carotene‐10′‐ol (2) and (all‐E,3R)‐10′‐apo‐β‐carotene‐3,10′‐diol (5) have been isolated from petals of one yellow species and various whitish or yellow blend varieties of rose cultivars. Each (all‐E)‐compound is accompanied by a (Z)‐isomer, probably the (9Z)‐isomer. Diol 5 proved to be identical with galloxanthin, an apo‐10′‐carotenol previously isolated from the retina of chicken.
Sarcodictyin A and Sarcodictyin B, Novel Diterpenoidic Alcohols Esterified by (E)‐N(1)‐Methylurocanic Acid. Isolation from the Mediterranean Stolonifer Sarcodictyon roseum
Authors: D'Ambrosio Michele , Guerriero Antonio , Pietra Francesco
Published: December 2004

The Mediterranean stolonifer Sarcodictyon roseum (= Rolandia rosea) (Cnidaria, Anthozoa, Alcyonaria, Stolonifera, Clavulariidae) is shown to contain two novel diterpenoidic alcohols esterified by (E)‐N(1)‐methyl‐urocanic acid (= E)‐3‐(l‐methyl‐lH‐imidazol‐4‐yl)acrylic acid). They are sarcodictyin A ( = (−)‐(4R,4a,R, 7R,10S,11S,12aR,lZ,5E,8Z)‐7,10‐epoxy‐3,4,4a,7,10,11,12,12a‐octahydro‐7‐hydroxy‐6‐(methoxycarbonyl)‐1,10‐dimethyl‐4‐(1‐methylethyl)benzocyclodecen‐11‐yl (E)‐3‐(1‐methyl‐lH‐imidazol‐4‐yl)acrylate; (−)‐1) and sarco‐dictyin B (the 6‐(ethoxycarbonyl analogue; (−)‐2). The assignment of the structures is mainly based on 1D‐ and 2D‐NMR data, as well as on chemical transformations of (−)‐1, such as transesterification with MeONa/MeOH giving methyl (E)‐N(1)‐methylurocanate (3) and the free alcohol (+)‐4 and reduction with LiAlH4 followed by benzoylation giving dibenzoate 7. Absolute configurations are based on Horeau's method of esterification of (+)‐4.
Azidinium‐Salze. 23. Mitteilung. Photolyse heterocylischer Azidinium‐Salze
Authors: Balli Heinz , Huys‐Francotte Martine , Schmidlin Fred
Published: December 2004

Photolysis of Heterocyclic Azidinium Salts

The photochemistry of some azidinium salts was investigated. Their photolusis led to a large variety of products which were isolated and identified. Reaction mechanisms involving singlet and triplet nitrene intermediates are discussed to explain the product formation.
L‐Carnitine. Novel Synthesis and Determination of the Optical Purity
Authors: Voeffray Robert , Perlberger Jean‐Claude , Tenud Leander , Gosteli Jacques
Published: December 2004

A new route to L‐carnitine (1) based on the resolution of th trimethylammonium derivative 5 is described. The enantiomeric purity of 1 is determined by 1H‐NMR of its O‐acetyl hydrochloride 11 using [Eu(hfc)3] as chiral shift reagent. The optical rotation of 1 with an enantiomeric purity ≥99% is [α] =−31.3° (c = 10, H2O).
Reactions of Chiral 2‐(tert‐Butyl)‐2H,4H‐1,3‐dioxin‐4‐ones Bearing Functional Groups in the 6‐Position and Diastereoselective Catalytic Hydrogenation to cis‐2,6‐Disubstituted 1,3‐Dioxan‐4‐ones
Authors: Noda Yoshihiro , Seebach Dieter
Published: December 2004

(R)‐5‐Bromo‐6‐(bromomethyl)‐2‐(tert‐butyl)‐2H,4H‐1,3‐dioxin‐4‐one (2) derived from (R)‐3‐hydroxybutanoic acid is used for substitutions and chain elongations at the side‐chain C‐atom in the 6‐position of the heterocycle (→3–6, 10–13). Subsequent simultaneous reductive debromination and double‐bond hydrogenation (Pd/C,H2)occurs with essentially complete diastereoselectivity (>98% ds), with H transfer from the face opposite to the t‐Bu group (→15–20, Table 1). Hydrolytic cleavages of the dioxanones then lead to enantiomerically pure β‐hydroxy‐acid derivatives (overall self‐reproduction of the stereogenic center of 3‐hydroxybutanoic acid or alkylation in the 4‐position of this acid with preservation of configuration).
Synthese makrocyclischer Ketone durch Ringerweiterung; ein neuer Weg zu(±)‐Muscon
Authors: Bienz Stefan , Hesse Manfred
Published: December 2004

Synthesis of Macrocyclic Ketones by Ring‐Enlargement Reactions; a New Path to (±)‐Muscone

A new synthetic route to macrocyclic ketones is described. Starting from 2‐nitrocycloalkanones, the ring‐enlarged compounds of the type 4 and 5 were prepared in three steps. Reduction of the NO2 group with Bu3SnH and azobisisobutyronitrile led in moderate yields to simple β‐keto‐esters which were quantitatively hydrolyzed and decarboxylated to the ketones of the type 8 and 9. The interesting fragrances Exaltone® (8a) and (±)‐muscone (9a) were prepared in this way in overall yields of 22 and 18%, respectively.
Kombinierte Anwendung von NOE‐Experiment und Molekül‐Mechanik‐Rechnungen zur Lösung eines stereochemischen Problems
Authors: Bigler Peter , Tintelnot Marina
Published: December 2004

Combined Application of NOE Experiment and Force‐Field Calculations for the Solution of a Stereochemical Problem

The determination of NO effects using modern NMR techniques yields valuable information on internuclear distances in molecules. The correct interpretation of these effects in highly flexible molecules with anisotropic internal motions can be improved in reliability and efficiency by the concomitant application of force field calculation. The evaluation of an additional parameter from the results of such a calculation, which can directly be correlated with the experimental data, is demonstrated. Nevertheless, inherent problems in both the NOE measurements and molecular mechanics should be taken into account for a careful interpretation of the results.
Agnatasterone A and B, Unusual Pregnane Steroids Isolated from the North‐East Atlantic Sponge Axinella agnata
Authors: Guella Graziano , Pietra Francesco
Published: December 2004

Two novel pregnatrienolones isolated in very small amounts from the North‐East‐Atlantic demosponge Axinella agnata (Tetractinomorpha, Axinellida) are unique in having C(2)C(3) (or C(3)C(4)), C(7)C(8), and C(16)C(17) bonds and a 12β‐OH group which, being strongly H‐bonded to a 20‐keto group, resists acylation. 1H‐ and 13C‐NMR spectroscopy of the steroids and of products of their selective epoxidation or reduction allow us to propose the structures (+)‐12β‐hydroxy‐5α‐pregna‐2,7,16‐trien‐20‐one ( = agnatasterone A, (+)‐1), and (+)‐12β‐hydroxy‐5α‐pregna‐3,7,16‐trien‐20‐one ( = agnatasterone B. (+)‐5), for the two steroids with minimal recourse to model compounds.
Synthesis of Aristotelia‐Type Alkaloids. Part III. (3R,4R)‐ and (3R,4S)‐1‐p‐menthene‐3,8‐diol and the corresponding racemates: Preparation and assignment of configuration
Authors: Burkard Stefan , Looser Martin , Borschberg Hans‐Jürg
Published: December 2004

A 1:1 mixture of the racemic trans‐ and cis‐1‐p‐menthene‐3,8‐diols ((±)‐3 and (±)‐4, resp.) was readily prepared in 3 steps starting from 3‐methyl‐2‐cyclohexen‐1‐one. The relative configuration of the diols, purified via the corresponding cyclocarbonates, was assigned by 1H‐NMR spectroscopy and found to be at variance with tentative claims in the literature. Optically active samples of 3 and 4 were prepared by resolution of the racemates with (R)‐1‐phenylethylamine. The absolute configuration of the resulting diols was determined by chemical correlation with standards of known absolute configuration.
Low‐Temperature X‐ray Crystal‐Structure Analysis of the Thermally Unstable Lithiated 2‐Butenyl tert‐Butyl Sulfide: A comparison with model ab initio MO calculations
Authors: Seebach Dieter , Maetzke Thomas , Haynes Richard K. , Paddon‐Row Michael N. , Wong Stephen S.
Published: December 2004

Single crystals of the N,N,N′,N′‐tetramethylethylenediamine (TMEDA) complex 6 of the title compound have been isolated. Compound 6 decomposes in the crystalline state above −20°. From the bond lengths and angles obtained by X‐ray crystal‐structure analysis (data collected at −70°), compound 6 is best described as a (E)‐1‐(tert‐butylthio)‐1‐lithio‐2‐butene with the double bond acting as an additional ligand on lithium (unsymmetrical allylic group). The S‐atom is in a cisoid arrangement in a common plane with the four C‐atoms of the butenyl system. The t‐Bu group and the Li‐atom are located above and below this plane. The structure is discussed with respect to the reactivity of 6 (α/γ reactivity). The gross structure is reproduced surprisingly well by an ab initio SCF MO calculation of the model lithiopropene‐1‐thiol 7(HS instead of t‐BuS, CH2 instead of CHCH3, no solvation of Li). The prominent difference is the symmetry of the allyllic moiety in the calculated structure.
Optically Pure Isoproterenol Analogues With Side Chains Containing an Amide Bond: Synthesis and biological properties
Authors: Märki Hans P. , Crameri Yvo , Eigenmann Rainer , Krasso Anna , Ramuz Henri , Bernauer Karl , Goodman Murray , Melmon Kenneth L.
Published: December 2004

The isoproterenol analogues 4a and 4b, synthesized as mixtures of Diastereoisomers, were shown to possess very potent β‐adrenoceptor agonistic activity. Therefore, the four possible diastereoisomers of 4a have been synthesized and tested for inotropic activity. The (6R, 2′R)‐diastereoisomer turned out to be the most interesting one. Consequently, also (6R,2′R)‐4b has been prepared and tested. For the diastereoselective synthesis, three variants have been elaborated: (i) coupling of epoxides 12 with amines 27 (Scheme 6); (ii) coupling of the activated glycol 17 with the amine 22 (Scheme 8); (iii) diastereoselective hydrogenation of the amino ketone 31 (Scheme 7). Both (6R,2′R)‐4a and (6R,2′R)‐4b show long lasting positive inotropic activity after intravenous as well as oral administration and are at least three times as potent as rac‐isoproterenol. In the anesthetized dog, a good separation of positive inotropic and positive chronotropic effects is observed. In conscious dogs, however, heart rate and contractile force increase to the same extent (possibly due to reflex tachycardia).
Polycyclopentane Als Steroid‐Analoga
Authors: Trachsel Marcel , Keese Reinhart
Published: December 2004

Polycyclopentanes as Steroid Analoga

The synthesis of linearly annellated pentaquinanes from a readily available triquinane is reported.
Light‐Induced Synthesis of Tricyclic Thiolane Derivatives from 2(5H)‐thiophenones via consecutive radical ring closure
Authors: Kiesewetter René , Graff Alan , Margaretha Paul
Published: December 2004

Two α,β‐unsaturated thiolactones, 5‐(2‐propynyl)‐2(5H)‐thiophenone (5) and 3,5‐di(2‐propenyl)−2(5H)‐thiophenone (6), were newly synthesized. Irradiation (λ = 300 nm) of 5 in MeOH containing cyclopentene afforded a 3:1 mixture of diasteroisomeric methyl 7‐thiatricyclo[6.4.0.02,6]dodec‐10‐ene‐12‐carboxylates (8a/8b), while irradiation of 6 in MeOH saturated with 2‐methylpropene gives a 3:2 mixture of diastereoisomeric methyl 3,3,9‐trimethyl‐5‐thiatricyclo[6.2.1.02,6]undecane‐1‐carboxylates (10a/10b).
1H‐and 13C‐NMR study of the dilithium naphthalene and its TMEDA complex
Authors: Benken Rainer , Günther Harald
Published: December 2004

Dilithium naphthalene (2) and its TMEDA complex 3 have been prepared, and their 1H‐and 13C‐NMR spectra were analyzed in terms of chemical shifts and coupling constants. From its Q value, 2 is characterized as delcoalized [4n] π system and the 1H ‐ as well as the 6Li‐NMR shifts classify the ion as strongly paratropic. For the quarternary C‐atoms, a down‐field shift of 30.4 ppm is observed. The conclusions drawn from the NMR parameters are compared with the results of MNDO calculations for naphthalene and biphenylene and their ions.
The Construction of New Proteins. Part III. Artificial folding units by assembly of amphiphilic secondary structures on a template
Authors: Mutter Manfred , Altmann Eva , Altmann Karl‐Heinz , Hersperger René , Koziej Pjotr , Nebel Kurt , Tuchsecherer Gabriele , Vuilleumier Stéphane , Gremlich Hans‐Ulrich , Müller Klaus
Published: December 2004

A new general strategy for the construction of artificial proteins with predetermined tertiary structure is presented. Amphiphilic α‐helix and β‐sheet‐forming oligopeptides are assembled on a multifunctional ttemplate molecule which directs the peptide blocks to adopt characteristic folding topologies. The design, synthesis, and conformational properties of these template‐assembled synthetic proteins (TASP) are exemplified for βαβ‐, α‐helix‐bundle‐ and β‐barrel‐like tertiary structures using specially designed oligopeptides as template molecules. In contrast to linear polypeptide chains of comparable molecular weights, these conceptually novel marcromolecules are readily accessible to chemical synthesis and exhibit excellent solubility in a number of solvents. Experimental evidence is provided for a template‐induced intramolecular folding to secondary and tertiary structures in aqueous solutions. This approach opens new prospects for the chemical construction of biomacromolecules with tailormade structural and functional properties.