bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of New Sialidase Inhibitors, 6‐Amino‐6‐Deoxysialic Acids
Authors: Baumberger Franz , Vasella Andrea , Schauer Roland
Published: December 2004

The synthesis of the 6‐amino‐6‐deoxysialic‐acid analogues 4, 5, and 6, is described. Mitsunobu reaction of the 1‐C‐nitroglycal 8, (PPh3, HCOOH, DEAD) gave the formiate 10 with inversion of configuration at C(3) (Scheme 2). Treatment of 10 with aq. NH3 and subsequent protection of the amino function gave the imines 14 and 15 (Scheme 3), which were transformed into the triflates 17. Substitution by azide, deprotection, and N‐acetylation gave the anormeric 2‐acetamido‐3‐azido‐1‐deoxy‐1‐nitro‐D‐mannoses 16 and the enol ether 18. Chain elongation of the nitro azides 16 followed by hydroylsis gave the nonulosonates 20/22, which upon reduction yielded the diols 23 and 24, respectively (Scheme 4). The diol 23 was transformed into the sialic‐acid analogues 5, 6, and 32 by ozonolysis, transfer hydrogenation, hydorgenolysis, and deprotection (Scheme 5), and the diol 24 into 4 by a similar reaction sequence. The sialic‐acid analogues 4 and 6 inhibit bacterial and viral sialidases competitively. The inbibitor constants for this enzyme from Vibrio cholerae are 0.12 mm for 4 and 0.19 mm for 6, respectively. The activity of fowl plague virus sialidase was reduced by 17% and 36% under the influence of 4 and 6, respectively, at a concentration of 0.1 mM. Compound 5 was inactive.
Slowly Interconverting Conformers of The Briarane Diterpenoids Verecynarmin B, C, and D, Isolated from the nudibranch mollusc Armina maculata and the pennatulacean octocoral Veretillum cynomorium of East Pyrenean waters
Authors: Guerriero Antonio , D'Ambrosio Michele , Pietra Francesco
Published: December 2004

The novel briarane diterpenoids verecynarmin B(=(−)‐(1R*, 10S*, 11R*, 4E, 12Z)‐briara‐4,7,12,17,‐tetraen‐14‐one; (−)‐4); verecynarmin C (=(−)‐(1R*, 10R*, 11S*, 4E, 12Z)−11‐hydroxybriara‐4,7,12,17‐tetraen‐14‐one; (−)‐5); and verecynarmin D (=(−)‐(1R*, 10R*, 11R*, 4E, 12E)‐13‐chloro‐11‐hydroxybriara‐4,7,12,17,‐tetraen‐14‐one; (−)‐6) are reported here as constituents of both the Mediterranean nudibranch mollusc Armina maculata (Rafinesque) and its prey, the pennatulacean octocoral Veretillum cynomorium (PALLAS). The structural assignments rest mainly on (i) establishing that these briaranes occur in solution as two stable conformers which interconvert slowly (ca. 10 time per second at r.t. according to dynamic NMR) by 180° flipping of the C(4)C(5) group in the ten‐membered ring (Scheme 1), (ii) deriving, for both conformers, 1H, 1H coupling constants from 1D spectra, as well as 1H, 1H, 13C, 1H, and 13C, 1H, and 13C, 13C, correlations from 2D experiments; (iii) subjecting the briaranes to SeO2 oxidation at the C(16) methyl group with isomerization at the C(4)=C(5) bond to give, in each case, only one observable molecular species as shown by NMR spectroscopy (Scheme 2).
15N‐Markiertes 3‐(Dimethylamino)‐2,2‐dimethyl‐2H‐azirin zur mechanistischen Untersuchung von Reaktionen mit NH‐aciden Heterocyclen
Authors: Ametamey Simon M. , Hollenstein Roger , Heimgartner Heinz
Published: December 2004

15N‐Labelled 3‐(Dimethylamino)‐2,2‐dimethyl‐2H‐azirine for Mechanistic Studies of Reactions with NH‐Acidic Heterocycles

The synthesis of 3‐(dimethylamino)‐2,2‐dimethyl(1‐15N)‐2H‐azirine (1*) was accomplished via reaction of 1‐chloro‐N,N,2‐trimethyl‐1‐propenylamine (9) and sodium (1‐15N) azide (Scheme 3). The earlier reported reactions of 1 with saccharin (10, Scheme 4), phthalimide (12, Scheme 5), and 2H‐1,3‐benzoxazin‐2,4(3H)‐dione (16, Scheme 6) were repeated with 1*, and the position of the 15N‐label in the products was determined by 15N‐NMR spectroscopy. Whereas the postulated reaction mechanisms for 10 and 12 were confirmed by these experiments, the mechanism for the reaction of 16 had to be revised. With respect to the position of 15N in the products 17 and 18, a new mechanism is formulated in Scheme 7. Treatment of 5,5‐dimethyl‐1,3‐oxazolidine‐2,4‐dione (19) with 1* led to 3,4‐dihydro‐2H‐imidazol‐2‐on 20 in which only N(3) was labelled. The mechanism of a ring expansion and transannular ring contraction as shown in Scheme 8 is in agreement with this finding.
Novel Aplysinopsin‐Type Alkaloids from Scleractinian Corals of the Family Dendrophylliidae of the Mediterranean and the Philippines. Configurational‐assignment criteria, stereospecific synthesis, and photoisomerization
Authors: Guella Graziano , Mancini Ines , Zibrowius Helmut , Pietra Francesco
Published: December 2004

From the scleractinian coral Tubastraea sp. (Dendrophylliidae) collected at Palawan, Philippines, 3′‐deimino‐3′‐oxoaplysinopsin (4) and 6‐bromo‐3′‐deimino‐3′‐oxoaplysinopsin (6) are now isolated as 5:2 mixtures of (E/Z) stereoisomers. The 3′‐deimino‐2′,4′‐bis(demethyl)‐3′‐oxoaplysinopsin (7) and 6‐bromo‐3′‐demino‐2′,4‐bis(demethyl)‐3′‐oxoaplysinopsin (5) are isolated as 2:3 and 1:1 (E/Z) mixtures, respectively, from another dendrophylliid, Leptopsammia pruvoti, collected near Marseille, Mediterranean coast of France. Larger amounts of these and related compounds, needed for a full structural determination, are obtained by synthesis. Thus, condensations of indol‐3‐carboxaldehyde (9) or of its 6‐bromo derivative 14 with hydantoin (15), 3‐methylhydantoin (11), or 1,3dimethylhydantoin (10) give the prevalent natural aplysinopsins with high stereospecificity. The minor stereoisomers (Z)‐4, (Z)‐6, (E)‐7, and (E)‐5 are obtained by (E/Z) photoisomerization under UV light of the condensation mixtures. The configuration is assigned from larger HC(8)/C(5′) 1H, 13C couplings in the (E) than in the (Z) isomer, and, in the case of 4 and 6, from NOE enhancement at MeN(2′) on irradiation at HC(8). The stereospecificity of the condensations is attributed to steric inhibition to planarity in the rate‐limiting transition states, due to N(2′)/HC(2) repulsion with (Z)‐4 and (Z)‐6, or to C(5′)O/HC(2) repulsion with (E)–7 or (E)‐5. As the aplysinopsins undergo (E/Z ) phostoisomerization also under the daylight conditions of the laboratory, their isomeric composition in nature can not be presently assessed.
Stereospecific Synthesis of 2‐Oxazinyl‐4‐oxoazetidinecarbamates Starting from a 1,2‐Diazepine. A new type of intramolecular transbenzoylation
Authors: Fritz Hans , Henlin Jean‐Michel , Tschamber Théophile , Streith Jacques , Riesen Andreas , Zehnder Margareta
Published: December 2004

Azeitidinodiazepines4band4creact with acylnitroso dienophiles5a–c, specifically from their convexe α‐side, but in a non‐regiospecific way, leading thereby stereospecifically to the expected adducts6a–dand7a–d. The three‐dimensional structures of6aand7awere determined by X‐ray analyses which corroborated their NMR data. OsO4cis‐glycolization occurred in good yield with the inverse adducts7aand7eand led to the rearranged products10. These latter ones result from an intramolecular N‐ to O‐transbenzoylation of the short‐lived intermediates9followed by fragmentation of the animal function. X‐Ray analysis of7ashowed the N(10) atom to be pyramidal, a result which demonstrates that it does not have any pronounced benzamide character; otherwise no such N‐ to O‐transbenzoylation would have taken place. Structure and relative configuration of10awere ascertained by X‐ray analysis which confirmed its NMR data as well as the stereochemical outcome of its formation.
Aldehyde Enol Esters as Novel Chain Terminators in Cationic Olefin Cyclizations
Authors: Simmons Dana P. , Reichlin Daniel , Skuy David
Published: December 2004

Citronella (1) has been transformed into enol acetates 2 which have been cyclized with various Lewis and Brönsted acids to dihydrocyclocitral (4). Application of this methodology to the synthesis of mono‐ and bicyclic ring systems has been examined.
Synthesis of Ethyl (2RS,3SR)‐1‐Tosyl‐3‐Vinylazetidine‐2‐carboxylate and ethyl (2RS,E)‐3‐ethylidene‐1‐tosylazetidine‐2‐carboxylate (=rac‐ethyl N‐tosylpolyximate)
Authors: Bauman Hans , Duthaler Rudolf O.
Published: December 2004

The synthesis of 3‐ethylideneazetidine‐2‐carboxylic acid (=polyoximic acid; 3) is a approached in two different ways leading to potential precursors of 3. The first way involved a ring closure to a vinyl‐subsatituted azetidin. Thus, Ireland‐Claisen rearrangement of the Boc‐glycinates 6 and 10 of (Z)‐ and (E)‐2‐butene‐1,4‐diol afforded, after exchange of the N‐protecting groups, the isomeric 2‐(tosylamino)‐3‐vinylbutanolides 13 and 14 with high stereoselectivity. Only the cis‐isomer 14 could be further transformed to 3‐(bromomethyl)‐2‐(tosylamino)‐4‐pentenoate 17, and in a smoth cyclization with K2CO3, to trans‐3‐vinylazetidtene‐2‐carboxylaze 18 (Scheme 2). In the second approach, the 3‐ethylidene isomer 19 of 18 was obtained more directly by a [2+2] cycloaddition, together with the two isomers 23 and 24, from methlallene 20 and (tosyliminno)acetate 21 (Scheme 3). The main product of this reaction was, however, 2‐(tosylamino)‐4‐hexinoate 22, the product of an ene reaction.
Acid‐Catalyzed Rearrangements for a Diastereoselective Entry into a New Fused Hexacyclic Heterocycle: (5RS,7aRS,12RS,14aRS,)‐4,5,7a,11,12,14,14a‐octahydro‐5,12‐dimethyl‐diindolo [1,7‐bc: 1′,7′‐gh][2,6] naphthyridine
Authors: Papageorgiou Christos , Borer Xaver
Published: December 2004

The title compound 1 was obtained in 10.3% overall yield via two acid‐catalyzed rearrangements and pyrrolidine formation. Thus, bi‐oxindole 6 afforded exclusively the thermodynamically stable cis‐diazachrysene 7 which, after allylation, followed by aza‐Claisen rearrangement gave alcohol 2. Pyrolytic ring closure of the latter yielded 1 in highly diastereoselective fashion.
Tandem cheletropic additions of sulfur dioxide to [2.2.2]hericene. The ‘barrelene effect’
Authors: Birbaum Jean‐Luc , Vogel Pierre
Published: December 2004

At 20°, [2.2.2]hericene ( = 2,3,5,6,7,8‐hexamethylidenebicyclo[2.2.2]octane;1) adds 2 equiv. of SO2 to give successively mono‐sulfolene 13 and the bis‐sulfolene 14 (for thermodynamic and kinetic data, see Tables 1 and 2). Under forcing conditions (high concentration, long reaction time), no trace of tris‐sulfolene 15 could be detected. The inertia of bis‐sulfolene 14 is attributed to the ‘barrelene effect’ which destabilizes the tris‐sulfolene 15.
Efficient Synthesis of 1,2‐Bis(2,2′‐bipyridinyl)ethane and 1,2‐bis(1,10‐phenanthrolinyl)ethane ligands by oxidative coupling of the corresponding monomeric methylene carbanions
Authors: Lehn Jean‐Marie , Ziessel Raymond
Published: December 2004

Several dimeric 1,2‐bis (2,2′‐bipyridinyl)ethane (1,2,6,7, and 9 and 1,2‐bis(1,10‐phenanthrolinyl)) ethane (3,4, and 5) ligands have been synthesized in high yield by oxidative coupling of the corresponding monomeric methylene carbanions using as oxidating agents Br2, I2, and 1,2‐dibromoethane. The structure of the compounds obtained from three tetramethyl‐2,2′‐bipyridines and one tetramethyl‐1,10‐phenanthroline have been assigned on the basis of their 1H‐NMR spectra. The electronic absorption and emission properties of these new ligands are reported. They display intense fluorescence spectra.
Synthese der Spermidin‐Alkaloide (±)‐Inandenin‐10‐ol, Inandenin‐10‐on und (±)‐Oncinotin
Authors: Bienz Stefan , Guggisberg Armin , Wälchli Rudolf , Hesse Manfred
Published: December 2004

Syntheses of the Spermidine Alkaloids (±)‐Inandenin‐10‐ol, Inandenin‐10‐one, and (±)‐Oncinotine

New syntheses of the title compounds using two‐ring‐enlargement reactions are described. Starting from the aldehyde 1, the corresponding 4′‐aza derivative 15 could be obtained by reductive amination with the appropriate and protected spermidine derivative 14 (Scheme 4). Enlargement of the carbocyclic ring in 15 by five members gave, after further transformations, the hydroxylactam 18. Transamidation of 18, the second ring‐enlargement step, led to (±)‐inandenin‐10‐ol (7;22.9% overall yield) and, after oxidation, to inandenin‐10‐one (8; 22.5%, overall yield). (±)‐Oncinotine 6 was synthesized by two pathways (Scheme 6): protection of the terminal NH2 group by treatment with the Nefkens reagent and replacement of the OH group by Cl gave 24, which by thermal transamidation followed by direct ring closure led to the oncinotine derivative 26. The same intermediate could be obtained in higher yield via 28 by oxidation and protection of 18 followed by transamidation and reductive ring closure. Treatment of 26 with hydrazine finally gave (±)‐oncinotine 6 in 15.9% overall yield.
Synthese des Flechtenmakrolids (+)‐Aspicilin mit Photolactonisierung als Schlüsselreaktion
Authors: Quinkert Gerhard , Heim Nana , Glenneberg Jürgen , Döller Uwe , Eichhorn Mathias , Billhardt Uta‐Maria , Schwarz Christine , Zimmermann Gottfried , Bats Jan W. , Dürner Gerd
Published: December 2004

Synthesis of the Lichen Macrolide (+)‐Aspicilin Using Photolactonization as a Key Reaction

(+)‐Aspicilin, obtained from a lichen source of the Black Forest, has been proven to have the absolute configuration depicted by formula la. It is easily built up from phenol (14a), 1,9‐nonanediol (13a), and (−)‐(S‐) methyloxiarane (6) (cf. Scheme 2). The latter building block provides the first stereogenic center C(17). The heterocycle is produced by photolactonization, fairly early during the course of the synthesis. The second stereogenic center is generated diastereoselectively at C(6) in compound 8, conveniently available from photolactone 9a or 9b/9c. Its absolute configuration depends on the kind of reducing agent and is controlled by long‐range conformational transmission of chiral information. To explore the cause of stereoselection, 2D‐NMR spectroscopy, X‐ray structural analysis, and/or computer‐aided conformational search followed by energy minimization have been used extensively, revealing the importance of the local conformation of the lactone moiety. Compound 8, on treatment with Yamamoto's reagent, affords pre‐target compound 7a almost exclusively. The latter compound, on pyridine‐accelerated dihydroxylation with OsO4, gives preferentially (+)‐Aspicilin.
The Structure of the Polycyclic Nonadecapeptide Ro 09‐0198
Authors: Kessler Horst , Steuernagel Stefan , Will Martin , Jung Günther , Kellner Roland , Gillessen Dieter , Kamiyama Tsutomu
Published: December 2004

The conventional determination of the amino‐acid sequence of the peptide antibiotic Ro 09‐0198 was prevented by four cyclizations via side chains. The joint application of NMR spectroscopy at highest field and automated Edman degradation yielded a complete determination of the connectivity pattern. The three‐dimensional structure derived from NOE data exhibits an interesting separation of amino acids with hydrophilic and hydrophobic side chains.
The Reaction Volume for the Equilibrium between the Lanthanide (III) ennea‐ and octaaqua lons as a diagnostic aid for their water‐exchange mechanisms. Preliminary Communication
Authors: Laurenezy Gabor , Merbach André E.
Published: December 2004

The equilibrium between [Ce(H2O)9]3+ and [Ce(H2O)8]3+ has been followed in aqueous solution at 298 K by variable‐pressure UV spectroscopy at 295 nm. The dervied volume of reaction for the dissociation of this enneaaqua ion is ΔV0 = +10.9 cm3. mol−1. This value, together with the previously determined activation volume, ΔV≠ = −6 cm3. mol−1, for H2O exchange on [Ln(H2O)8]3+ (Ln = Tb to Tm), allows the assignment of an associative interchange Ia mechanism on these octaaqua ions.
Bathophenanthroline‐ruthenium(II) complexes as non‐radioactive labels for oligonucleotides which can be measured by time‐resolved fluorescence techniques
Authors: Bannwarth Willi , Schmidt Dieter , Stallard Robert L. , Hornung Claudia , Knorr Reinhard , Müller Francis
Published: December 2004

The specific attachment of bathophenanthroline‐ruthenium(II) complexes as non‐radioactive label molecules to synthetically 5′‐NH2‐modified oligonucleotides is described. After excitation by light pulses, the fluorescence of these labels can be measured by a time‐resolved mode woth high sensitivity. No quenching takes place due to coupling of the Ru complexes to the DNA. Ru‐complex‐labelled oligonucleotides still hybridize specifically to complementary DNA sequences, and no quenching is observed in the course of the hybridization process.
Crystal Structure and Electron‐Density Distribution of Two [1.1.1] Propellane Derivatives at 81 K
Authors: Seiler Paul , Belzner Johannes , Bunz Uwe , Szeimies Günter
Published: December 2004

The molecular structure and electron‐density distribution of two [1.1.1]propellane derivatives have been determined from accurate single‐crystal X‐ray diffraction measurements at 81 K. The crystals of these highly reactive compounds (both are liquid at room temperature) were grown directly on the X‐ray diffractometer at ca. 208 and 228 K, respectively. Both compounds crystallize in the space group P21/c with one molecule in the asymmetric unit. The symmetry of the propellane C‐atom skeleton is close to D3h for both molecules. The distances between the two bridgehead C‐atoms are 1.587 and 1.585 Å, and the mean lengths of the propellane side bonds are 1.525 and 1.528 Å, respectively. The deformation density peaks of the propellane side bonds (ca. 0.25 e/Å3) lie somewhat outside the internuclear connection lines and so correspond to ‘bent bonds’ as expected. On the other hand, the difference electron density between the bridgehead nuclei is slightly negative in both molecules. An interesting feature, observed in these difference maps, is presence of a diffuse, positive difference density at each inverted C‐atom, outside the bridgehead bond, a probable site of electrophilic attack.
Photochemistry of Thiophen‐2(5H)‐ones
Authors: Kiesewetter René , Margaretha Paul
Published: December 2004

Mechanistic evidence for the light‐induced ring opening of thiophen‐2(5H)‐ones 1 in alcohols affording α, β‐unsaturated mercapto esters 2 is presented. Regio‐and stereochemical aspects of the ring closure of alkenylthio (type 3) radicals 15 and 17 to S‐heterocycles 16 and 18, of 3‐thiahex‐5‐enyl radicals 4 to (tetrahydrothien‐3‐yl)methyl radicals 6 and of (2,3‐dihydrothien‐3‐yl)methyl radicals 30 (type 7, but‐3‐enyl radicals) to cyclopropane‐methyl radicals 29 are discussed. Irradiation (λ 350 nm) of 1 in cyclohexane in the presence of 2,3‐dimethylbut‐2‐ene affords [2 + 2] cycloadducts 14 albeit in very low yields.
A New Method for the Preparation of (E)‐3‐Acylprop‐2‐enoic Acids
Authors: Obrecht Daniel , Weiss Bettina
Published: December 2004

A new method for the preparation of (E)‐3‐acylprop‐2‐enoic acids ( = (E)‐3‐acylacrylic acids) of type II via acid‐catalyzed isomerization of the corresponding 3‐acylprop‐2‐ynal acetals of type I (Scheme 1) has been found. The described reaction gives a rapid and quite general access to these compounds known to exhibit a number of interesting biological activities. Some studies toward the elucidation of the reaction mechanism have been made, and a hypothetical mechanism is proposed.
Biosynthesis of Homoterpenes in Higher Plants
Authors: Boland Wilheim , Gäbler Andreas
Published: December 2004

In higher plants, the two homoterpenes 4,8‐dimethyinona‐1,3,7‐triene (1) and 4,8,12‐trimethyltrideca‐1,3,7,11‐tetraene (2) are synthesized from the regular terpene alcohols nerolidol and geranyllinalool by fragmentation into the homoterpene and butenone. The biosynthetic pathway is evidenced by conversion of (2H)nerolidol in Hoya purpureo‐fusca, Magnolia liliiflora nigra, Robinia pseudoacacia, and Philadelphus coronarius.
Isotope Effects on the Lipophilicity of Deuterated Caffeines
Authors: Bechalany Antoine , El Tayar Nabil , Carrupt Pierre‐Alain , Testa Bernard , Falconnet Jean‐Bernard , Cherrah Yahia , Benchekroun Youssef , Brazier Jean‐Louis
Published: December 2004

In the present study, it is confirmed that the deuteration of CH groups is accompanied by a small but genuine decrease in lipophilicity. The lipophilicity of deuterated isotopomers of caffeine was measured by reversed‐phase HPLC. Overall, lipophilicity was shown to decrease when going from unlabelled caffeine to the three isomeric trideuterated caffeines, then to the three isomeric hexadeuterated caffeines, and finally to nonadeuterated caffeine. In addition, position‐specific effects were also proven. E.g. (7‐methyl‐2H3)caffeine experienced a smaller isotope effect than its two positional isomers. Both a cavity factor (decreased volume of deuterated isotopomers) and intramolecular electronic effects are postulated to operate.
Synthese von (R)‐β, β‐Carotin‐2‐ol und (2R, 2′R)‐β, β‐Carotin‐2,2′‐diol
Authors: Gut Samuel , Wolleb Heinz , Pfander Hanspeter
Published: December 2004

Synthesis of (R)‐β, β‐Caroten‐2‐ol and (2R, 2′R)‐β, β‐Carotene‐2,2′‐diol

Starting from geraniol, the two carotenoids (R)‐β, β‐caroten‐2‐ol (1) and (2R, 2′R)‐β, β‐carotene‐2,2′‐diol (3) were synthesized. The optically active cyclic building block was obtained by an acid‐catalysed cyclisation of the epoxide (R)‐4. The enantiomeric excess of the product was > 95 %.
A Regiospecific Photochemical Rearrangement of 2‐Azabenzotricyclo[5.2.2.01,5]‐ to 2‐Azabenzotricyclo[6.2.1.01,5]undecatrienone
Authors: Trifonov Latchezar S. , Dimitrov Valentin S. , Orahovats Alexander S.
Published: December 2004

The 2‐azatricyclo[5.2.2.01,5]undeca‐4,8,10‐trien‐3‐ones 1a and 1b gave on irradiation the 2‐azatricyclo‐[6.2.1.01,5]undeca‐4,6,9‐trien‐3‐ones 2a and 2b, respectively. The rearrangement was found to be solvent‐, oxygen‐, and wavelength‐independant.
Synthèse énantiospécifique des acides (+)‐(2R)‐ et (−)‐(2S)‐éthyl‐6‐dihydro‐3,4‐méthyl‐2‐oxo‐4–2H pyranecarboxylique‐5
Authors: Deschenaux Pierre‐François , Kallimopoulos Thomas , Stoeckli‐Evans Helen , Jacot‐Guillarmod André
Published: December 2004

Enantiospecific Synthesis of (+)‐(2R)‐ and (−)‐(2S)‐6‐Ethyl‐3,4‐dihydro‐2‐methyl‐4‐oxo‐2H‐pyran‐5‐carboxylic Acid

The two enantiomers (−)‐(2S)‐ and (+)‐(2R)‐6‐ethyl‐3,4‐dihydro‐2‐methyl‐4‐oxo‐2H‐pyran‐5‐carboxylic acid ((S)‐ and (R)‐7) have been synthesized from (+)‐(3S) and (−)‐(3R)‐3‐hydroxybutanoates, respectively (Scheme 1). By reduction and decarboxylation, the tetrahydro‐2H‐pyranols (2R, 4R, 6S)‐ and (2S, 4S, 6R)‐13, respectively, were obtained with an enantiomeric excess of ≥ 93%.
Synthesis of 4‐Alkoxy‐1,3‐oxazol‐5(2H)‐ones, Precursors of 1‐alkoxy substituted nitrile ylides
Authors: Bozhkova Nina , Heimgartner Heinz
Published: December 2004

4‐Alkoxy‐1,3‐oxazol‐5(2H)‐ones of type 4 and 7 were synthesized by two different methods: oxidation of the 4‐(phenylthio)‐1,3‐oxazol‐5(2H)‐one 2a with m‐chloroperbenzoic acid in the presence of an alcohol gave the corresponding 4‐alkoxy derivatives 4, presumably via nucleophilic substitution of an intermediate sulfoxide (Scheme 2). The second approach is the BF3‐catalyzed condensation of imino‐acetates of type 6 and ketones (Scheme 3). The yields of this more straightforward method were modest due to the competitive formation of 1,3,5‐triazine tricarboxylate 8. At 155°, 1,3‐oxazol‐5(2H)‐one 7b underwent decarboxylation leading to an alkoxy‐substituted nitrile ylide which was trapped in a 1,3‐dipolar cycloaddition by trifluoro‐acetophenone to give the dihydro‐oxazoles cis‐ and trans‐9 (Scheme 4). In the absence of a dipolarophile, 1,5‐dipolar cyclization of the intermediate nitrile ylide yielded isoindole derivatives 10 (Schemes 4 and 5).
Festkörper‐Polymerisation eines ‘Push‐Pull’‐Diacetylens
Authors: Galli Roberto , Neuenschwander Markus , Engel Peter
Published: December 2004

Solid‐State Polymerisation of a ‘Push‐Pull’‐Diacetylene

Solid‐state polymerisation of ‘push‐pull’‐diacetylene 5‐(diphenylamino)‐1‐phenylpenta‐2,4‐diyn‐1‐one (1d), initiated by heating of crystals of 1d at 90°, gives ‘push‐pull’ poly‐diacetylene 2d. X‐Ray results and spectroscopic data of monomer 1d as well as of polymer 2d are discussed.
Synthesis of cis and trans Whisky and Cognac lactones by the regiocontrolled alkylation of 2‐(trimethylsiloxy)furan
Authors: Jefford Charles W. , Sledeski Adam W. , Boukouvalas John
Published: December 2004

The racemic cis‐ and trans‐5‐butyltetrahydro‐4‐methylfuran‐2‐ones ( = whisky lactones) and their higher homologues tetrahydro‐4‐methyl‐5‐pentylfuran‐2‐ones ( = cognac lactones) have been prepared in 2–3 steps from 2‐(trimethylsiloxy)furan. Regioselective alkylation of the latter afforded the 5‐butyl‐ and 5‐pentylfuran‐2(5H)‐ones which served as precursors for the stereocontrolled construction of either diastereoisomer of the beverage lactones. The structure and tautomerization of the diazomethane adducts of these 5‐alkylfuran‐2(5H)‐ones are also described.
[4 + 2]‐Cycloadditionen von α, β‐ ungesättigten hydrazonen. Teil3. Isothiazolo[4,5‐b]pyridin‐3(2H)‐on‐1,1‐dioxide (= 4‐azasaccharine)
Authors: Waldner Adrian
Published: December 2004

[4 + 2] Cycloaddition of α, β‐Unsaturated Hydrazones: Isothlazolo[4,5‐b]pyridin‐3(2H)‐on 1,1‐Dioxides (= 4‐Azasaccharine Derivatives)

The [4 + 2] cycloaddition of α, β ‐unsaturated hydrazones of type 1 (1‐azabuta‐1,3‐dienes) with isothiazol‐3(2H)‐on 1,1‐dioxide derivatives 10 affords, depending on the solvent used, picolinamides 15 or 17, 4,7‐dihydro‐4‐azasaccharine 14 or 4‐azasaccharine derivatives 16 (Scheme 4). The course of the reaction is mainly influenced by the substituent R of the dienophile 10.
Catalytic effect of tetrabutylammonium fluoride in the preparation of secoribo‐nucleosides
Authors: Hakimelahi Gholam H. , Khalafi‐Nezhad Ali
Published: December 2004

A general and rapid procedure is developed for the preparation of secoribo‐nucleoside analogues. Bu4NF has a marked effect on the condensation of guanine (5) with 2‐(chloromethoxy)ethyl benzoate (2) or 1‐halo‐2‐(chloromethoxy)ethanes 12 and 16. Condensation and deprotection of the acyl protecting group and nucleophilic displacement of the halogen atoms to yield 9‐[(2‐hydroxyethoxy)methyl] guanine (9) occurred in one step.
New aromatic musk odorants: Design and synthesis
Authors: Fehr Charles , Galindo José , Haubiichs Rolf , Perret Roland
Published: December 2004

By appropriate structural modification of known musk odorants, new strong musk odorants have been discovered. Incorporation of supplementary CH3 or CH2 groups into the basic musk skeleton of type G only slightly modifies the global shape of the molecule but leads to densely packed structures of enhanced lipophilicity. For the construction of these highly substituted 1,2,3,4‐tetrahydronaphthalenes, new annulation sequences (intramolecular mono‐ and dialkylations; see Schemes 3,6, and 8) have been developed and, in certain cases, the design of the target molecules was dictated by both structure‐activity‐relationship and synthetic considerations (e.g. 46 and 47, Scheme 6). This work also presents an original solution to an analytical problem: the distinction between a C2‐ and a Cs‐symmetrical aromatic hydrocarbon (viz. 71 and 72) by conversion into a [Cr(CO)3arene]complex.
Synthesis and Structure of a New Type of Chiral Organoiron and Organoruthenium Complexes
Authors: Adams Christoph M. , Hafner Andreas , Koller Markus , Marcuzzi Alessandro , Prewo Roland , Solana Isabel , Vincent Beverly , von Philipsborn Wolfgang
Published: December 2004

The synthesis of 36 [Fe(CO)2L1(η4‐diene)], three [Fe(CO)2L1(η4‐encne)], and five [Ru(CO)2L1(η4‐diene)] complexes (L1 = Ph3P, Et3P, (EtO)3P, (MeO)3p, C6H11NC) by thermal, selective CO ligand displacement in the corresponding tricarbonyl precursor complexes is described. In a second step, photochemical CO displacement by another phosphorus ligand L2 leads to a new type of η4‐diene complexes with a centre of chirality at the metal atom (Fe, Ru). 23 Fe and three Ru complexes of this type have been prepared and characterized. In the case of complexes with unsymmetrical dienes, racemic diastereoisomers are formed which can be separated by chromatographic methods. The molecular structures of [Fe(CO)(Ph3P)((MeO)3P)(buta‐1,3‐diene)] (52), [Fe(CO)(Ph3P)((MeO)3P)(isoprene)] (58) and [Fe(CO)(Et3P)(EtO)3P(hexa‐2,4‐dienal)] (62a) were determined by X‐ray diffraction. All complexes were investigated by 13C‐, 31P‐ and, in part, 1H‐NMR spectroscopy. At low temperatures, conformational isomers (rotamers) can be differentiated which probably arise from ψ rotation at the coordinated metal centre.
Synthesis of Peptides Containing α,α‐Disubstituted α‐Amino Acids by the Azirine/Oxazolone Method: The (12–20)‐Nonapeptide of the Ionophore Alamethicin
Authors: Wipf Peter , Heimgartner Heinz
Published: December 2004

The (12–20)‐nonapeptide Z‐Leu‐Aib‐Pro‐Val‐Aib‐Aib‐Glu (OBzl)‐Gln‐Pheol (10) of the ionophor alamethicin was synthesized by a new strategy, using 3‐amino‐2,2‐dimethyl‐2H‐azirines 2 as synthons for the α‐aminoisobutyric acid (Aib) moieties.
Synthesis of Derivatives of (1R*,10aR*)‐1‐Azido‐10‐benzylidene‐4‐(diethylphosphono)‐1,2,10,10a‐tetrahydro‐2‐oxo‐4H‐azeto[1,2‐a]pyrido[1,2‐d]pyrazin‐9‐ylium Bromide
Authors: Hakimelahi Gholam H. , Sardarian Ali R.
Published: December 2004

The synthesis of some derivatives of the title compound VI is described. Bromination of diethyl (cis‐3‐azido‐2‐oxo‐4‐styrylazetidin‐1‐yl)(pyridin‐2‐yl)methylphosphonate (6) in MeOH gave tricyclic β‐lactam 7, while similar bromination of diethyl (cis‐3‐azido‐2‐oxo‐4‐vinylazetidin‐1‐yl)(pyridin‐2‐yl)methylphosphonate (9) afforded tri‐cyclic β‐lactam 10. Mechanisms for these transformations are proposed (Schemes 1 and 2).
trans‐Disubstituted Cyclohexadienes via Sequential Addition of a Carbon Nucleophile and an Electrophile to (η6‐Benzene)tricarbonylchromium: Scope of Carbon Electrophiles
Authors: Kündig E. Peter , Cunningham Allan F. , Paglia Patrick , Simmons Dana P. , Bernardinelli Gérald
Published: December 2004

A regio‐ and stereoselective route from benzene to trans‐disubstituted cyclohexadienes via complexation of the arene to the tricarbonylchromium group is reported. The key step involves an alkylation/carbonylation sequence of the anionic tricarbonyl (η5‐cyclohexadienyl)chromium complex (3) which is readily obtained by the addition of 2‐lithio‐2‐methyldithiane (2) to (η6‐benzene)tricarbonylchromium (1; cf. Scheme 6). In situ reaction of 3 with alkyl halides (in THF, THF/HMPA, THF/DMPU), followed by oxidation (I2, Ce(IV)) or ligand exchange (CO, Ph3P, Et3N) produced, with complete stereo‐ and regioselectivity, trans‐5,6‐disubstituted cyclohexadienes (15 examples). The cyclohexadiene substituent originating from the alkyl halide in all cases is an acyl group which shows that CO insertion into the metal–alkyl bond precedes reductive elimination to form the cyclohexadiene product. When, in the reaction of 3 with Mel, NHS3 was used to induce carbonylation und decornplexation, the isomerized, conjugated 1,4‐cyclohexadiene 13 was obtained almost exclusively. The electrophile selectivity in the reactions with 3 is consistent with a nucleophilic, SN2‐like mechanism with a high preference for primary iodides. Chloride, ketone, and ester functions in the electrophile are unreactive and are tolerated; a primary alkyl iodide reacted selectively in the presence of a secondary iodide. In one case, the trans‐configuration in a cyclohexadiene product 7 was demonstrated by the Diels‐Alder reaction with maleic anhydride. High facial selectivity was observed in this reaction giving a single diastereoisomer resulting from endo‐addition of the dienophile to the diene face carrying the acyl group. The anionic intermediate 3 was trapped with Ph3SnCl, and an X‐ray analysis of the resulting cyclohexadienyl [Cr(CO)3(R)] complex 15 provides evidence for electrophile addition to the metal. In the solid state, the Ph3Sn group in 15 is trans‐configurated to the dithianyl substituent. The ready access to [Cr(arene)(CO)3] complexes, the high selectivity of the reactions reported here and the mild decomplexation provide rapid access to Cyclohexadienes that possess functionality and are attractive for further transformation.
A CD‐Spectroscopic Alternative to Methylation Analysis of Oligosaccharides: Reference Spectra for Identification of Chromophoric Glycopyranoside Derivatives
Authors: Wiesler William T. , Berova Nikolina , Ojika Makoto , Meyers Harold V. , Chang Mayland , Zhou Peng , Lo Lee‐Chiang , Niwa Masatake , Takeda Reiji , Nakanishi Koji
Published: December 2004

A microscale method for identifying the monosaccharide units and their linkages in oligosaccharides is presented. Sugar components are identified by UV and CD spectroscopy of chromophoric degradation products. CD spectral data for approximately 150 different glycopyranoside components are provided for use as reference spectra in the identification of unknown derivatives. Procedures for the conversion of oligosaccharides to monosaccharide subunits bearing 4‐bromobenzoate and 4‐methoxycinnamate chromophores have been developed based on acetolysis/bromination reactions for glycosidic cleavage of per (bromobenzoylated) oligosaccharides. The method offers an alternative means to conventional methylation analysis of oligosaccharides.
Reaktionen von 3‐(Dimethylamino)‐2H‐azirinen mit 1,3‐Benzoxazol‐2(3H)‐thion
Authors: Ametamey Simon M. , Heimgartner Heinz
Published: December 2004

Reaction of 3‐(Dimethylamino)‐2H‐azirines with 1,3‐Benzoxazole‐2(3H)‐thione

The reaction of 3‐(dimethylamino)‐2H‐azirines 2 with 1,3‐benzoxazole‐2(3H)‐thione (5), which can be considered as NH‐acidic heterocycle (pKaca. 7.3), in MeCN at room temperature, leads to 3‐(2‐hydroxyphenyl)‐2‐thiohydantoins 6 and thiourea derivatives of type 7 (Scheme 2). A reaction mechanism for the formation of the products via the crucial zwitterionic intermediate A′ is suggested. This intermediate was trapped by methylation with Mel and hydrolysis to give 9 (Scheme 4). Under normal reaction conditions, A′ undergoes a ring opening to B which is hydrolyzed during workup to yield 6 or rearranges to give the thiourea 7. A reasonable intermediate of the latter transformation is the isothiocyanate E (Scheme 3) which also could be trapped by morpholine. In i‐PrOH at 55–65° 2a and 5 react to yield a mixture of 6a, 2‐(isopropylthio)‐1,3‐benzoxazole (12), and the thioamide 13 (Scheme 5). A mechanism for the surprising alkylation of 5 via the intermediate 2‐amino‐2‐alkoxyaziridine Fis proposed. Again via an aziridine, e.g. H (Scheme 6), the formation of 13 can be explained.
Homogeneous and heterogeneous asymmetric reactions. Part 5. Diastereoselective and enantioselective hydrogenation of cyclic β‐keto esters on modifiedRaney‐nickel catalysts
Authors: Wittmann Gyula , Göndös György , Bartók Mihály
Published: December 2004

The hydrogenations of methyl 2‐oxoeyclopentanecarboxylate (1), ethyl 2‐oxocyelohexanecarboxylate (3), and 2‐methylcyclohexanone (5) on unmodifiedRaney‐Ni catalyst lead predominately to the formation of thecis‐hydroxy diastereoisomers of2,4, and6, respectively (Scheme 2). In the asymmetric hydrogenations on catalysts modified with chiral tartaric acid ((R,R)‐C4H6O6/Raney‐Ni and (R,R)‐C4H6O6/NaBr/Raney‐Ni), the predominance of thecis‐isomer increases significantly. The hydrogenations of β‐keto esters1and3proceed with an enantioselectivity of 10–15% on the modified catalysts, while the similar hydrogenation of5yields optically inactive6. The (1S,2R)‐enantiomers of thecis‐isomers of2and4are formed in larger quantity, whereas the (lR,2R)‐enantiomers of the correspondingtrans‐isomers predominate (Scheme 1). The enantioselective formation oftrans‐2andtrans‐4can be interpreted mainly in terms of the asymmetric hydrogenation of cyclic β‐keto esters through the keto form, while that of the correspondingcis‐hydroxy esters proceeds through the enol form.
Technical Procedures for the Syntheses of Carotenoids and Related Compounds from 6‐Oxo‐isophorone: Syntheses of (3R,3′R)‐Zeaxanthin. Part II
Authors: Soukup Milan , Widmer Erich , Lukáč Theodor
Published: December 2004

Starting from the readily available, optically active (4R)‐hydroxy‐2,2,6‐trimethylcyclohexanone (2), a new technical synthesis of (3R,3′R)‐zeaxanthin is described. According to a completely new C9+C2+C4 = C15 scheme, the ketone 2 was protected, ethynylated with Li‐acetylide, and the C11‐intermediate 6 was acetylated, followed by dehydration. The product 10 was protected, deprotonated, and subsequently reacted with methyl vinyl ketone to provide the C15‐propargylate 13. Reduction in situ of 13 with Vitride yielded the olefinic C15‐alcohol 11 which was transformed into the known C15‐Wittig salt 3. A double Wittig reaction of this salt with the C10‐dialdehyde 4 afforded nature‐identical zeaxanthin (1).
Structure and Synthesis of (±)‐Caudoxirene, a New Spermatozoid‐Releasing and ‐Attracting Pheromone from the Marine Brown Alga Perithalia caudata (Phaeophyceae, Sporochnales). Part V
Authors: Wirth Dieter , Boland Wilhelm
Published: December 2004

Cis‐3‐(trans‐1,2‐Epoxybut‐3‐enyl)‐4‐vinylcyclopentene ((±)‐4, caudoxirene) is a new gamete‐releasing and gamete‐attracting pheromone from the marine brown alga Perithalia caudata (Sporochnales). The key step of its synthesis is the diastereoselective alkylation of the aldehyde 8 with the [(phenylthio)allyl]titanium reagent 9 to yield the erythro‐β‐hydroxy sulfide 10 which affords 4 on sequential treatment with Me3O·BF4 and aq. NaOH. The lowest effective concentration of (±)‐4 for gamete‐release is found at 1.4 × 10−11 mol/l seawater.
Synthesis and biological evaluation of 14‐alkoxymorphinans. Part 7. 14,14′‐dimethoxy analogues of norbinaltorphimine: Synthesis and determination of their χ opioid antagonist selectivity
Authors: Schmidhammer Helmut , Ganglbauer Ernst , Mitterdorfer Jörg , Rollinger Judith M. , Smith Colin F. C.
Published: December 2004

The bimorphinans 6 and 7 have been prepared from 14‐O‐methylnaloxone (2) and 14‐O‐methylnaltrexone (3), respectively. The known compounds 2 and 3 were synthesized by a different route than the route described. Bimorphinan 7 possessed a similar χ receptor affinity to norbinaltorphimine (1) but had a reduced selectivity due to marked increases in μ and δ receptor affinity. Bimorphinan 6 was both a less selective and less potent χ antagonist than 1.
Stereoselective Synthesis of the C(19)‐to‐C(27) Segment of Rifamycin S
Authors: Born Marco , Tamm Christoph
Published: December 2004

The synthesis of diester 3, a synthon for the C(19)‐to‐C(27) segment of rifamycin S (1), is described, starting from the meso‐diester 4 (Schemes 2 and 3). Inversion of the configuration at the later C(23) and two aldol condensations with the lithium enolate 18 of 2,6‐dimethylphenyl propionate each producing two new chiral centres of threo‐configuration, led to the desired diester 3. The absolute configuration of the new chiral centres was proven by a single X‐ray analysis of intermediate 19 (Fig.) and by converting diester 3 into meso‐diester 25.
1H‐Phenalen‐1‐one: Photophysical Properties and Singlet‐Oxygen Production
Authors: Oliveros Esther , Suardi‐Murasecco Patricia , Aminian‐Saghafi Taraneh , Braun André M. , Hansen Hans‐Jürgen
Published: December 2004

The efficiency of aromatic ketones as singlet‐oxygen (1O2(1Δg)) sensitizers can vary considerably with the electronic configuration of their lowest triplet state and the solvent used. Near‐infrared measurements of tie luminescence of singlet oxygen have shown that the quantum yield of singlet‐oxygen production (ΦΔ) by 1H‐phenalen‐1‐one (1) is close to unity in both polar (ΦΔ= 0.97±0.03 in methanol) and non‐polar solvents (ΦΔ= 0.93±0.04 in benzene). Analysis of the absorption spectra of the ground state and phosphorescence measurements show that the lowest singlet and triplet states have dominant π, π* electronic configurations. The quantum yield of intersystem crossing (ΦISC) of1, determined by laser flash photolysis (partial‐saturation method), is equal to unity. In comparison with other aromatic ketones, these parameters are important for the discussion of the surprisingly high ΦISCof1and the efficient energy transfer from its triplet state to molecular oxygen. The 1H‐phenalen‐1‐one (1), being one of the most efficient singlet‐oxygen sensitizers in both polar and non‐polar media, could be used as a reference sensitizer, in particular in the area of relatively high energies of excitation.
Synthesis of Aristotelia‐Type Alkaloids. Part VIBiomimetic Synthesis of (+)‐Aristofruticosine
Authors: Beerli René , Borschberg Hans‐Jürg
Published: December 2004

(S)‐Perilla alcohol (5) was transformed into (S)‐7‐(phenylthio)‐p‐menth‐1‐en‐8‐amine (11) in five steps. Condensation of this building block with 1‐(4‐methoxyphenylsulfonyl)‐1H‐indole‐3‐acetaldehyde (12) led to the expected imine 15 which cyclized in 54% yield to protected 20‐(phenylthio)hobartine 16 upon exposure to anh. HCOOH. Treatment of this intermediate with an alkylating reagent led to (+)‐aristofruticosine protected in the indole moiety via an intramolecular, allylic nucleophilic displacement reaction. Subsequent reductive removal of the protecting group completed the first synthesis of the Aristotelia alkaloid (+)‐aristofruticosine ((+)‐4). This straightforward synthesis confirmed the tentative structure (+)‐4, proposed by Bick and Hai, and established the hitherto unknown absolute configuration of this metabolite.
C2‐Symmetric 4,4′,5,5′‐Tetrahydrobi(oxazoles) and 4,4′,5,5′‐Tetrahydro‐2,2′‐methylenebis[oxazoles] as Chiral Ligands for Enantioselective Catalysis Preliminary Communication
Authors: Müller Dieter , Umbricht Gisela , Weber Beat , Pfaltz Andreas
Published: December 2004

The synthesis of a series of enantiomerically pure, C2‐symmetric 4,4′,5,5′‐tetrahydro‐2,2′‐methylenebis[oxazoles] and 4,4′,5,5′‐tetrahydro‐2,2′‐bi(oxazoles) is reported. Copper complexes with anionic tetrahydromethylenebis[oxazole] ligands are efficient catalysts for the enantioselective cyclopropane formation from olefins and diazo compounds (up to 96% ee in the reaction of styrene with menthyl diazoacetate). Tetrahydrobi(oxazole)iridium(I) complexes were found to catalyze transfer hydrogenations of aryl alkyl ketones with i‐PrOH (up to 91% ee). Tetrahydrobi(oxazole)palladium complexes can be used as enantioselective catalysts for allylic nucleophilic substitution (up to 77% ee in the reaction of PhCHCHCH(OAc)Ph with NaHC(COOMe)2).
Electronic and Conformational Effects on the Lipophilicity of Isomers and Analogs of the Neurotoxin 1‐Methyl‐4‐phenylpyridinium (MPP+)
Authors: Altomare Cosimo , Carrupt Pierre‐Alain , El Tayar Nabil , Testa Bernard , Nagatsu Toshiharu
Published: December 2004

A number of isomers and analogs of the neurotoxin 1‐methyl‐4‐phenylpyridinium (MPP+) were examined for their lipophilic behavior. Their partition coefficients in the 1‐octanol/H2O system were measured by centrifugal partition chromatography (CPC), which, being much faster and markedly more precise than the classical shake‐flask method, proved a very promising alternative for assessing lipophilicity. A smaller‐than‐expected lipophilicity was shown by the ortho‐isomer of MPP+ (M2PP+) and is explained in terms of electronic effects and rigidity, as revealed by UV and NMR spectroscopy, and conformational analysis. Implications of lipophilicity in modulating the in vivo dopaminergic neurotoxicity of the examined compounds are also discussed.
Analogues of Sialic Acids as Potential Sialidase Inhibitors. Synthesis of C6 and C7 Analogues of N‐Acetyl‐6‐amino‐2,6‐dideoxyneuraminic Acid
Authors: Glänzer Brigitte I. , Györgydeák Zoltan , Bernet Bruno , Vasella Andrea
Published: December 2004

The piperidines 12–18, piperidmose analogues of Neu5Ac (1) with a shortened side chain, were synthesized from N‐acetyl‐D‐glucosamine via the azidoalkene 32 and tested as inhibitors of Vibrio cholerae sialidase. Deoxygenation at C(4) of the uronate 22, obtained from the known D‐GlcNAc derivative 20, was effected by β‐elimination (→ 23), exchange of the AcO at C(3) with a (t‐Bu)Me2SiO group and hydrogenation (→ 26; Scheme 1). Chain extension of 26 by reaction with Me3SiCH2MgCl gave the D‐ido‐dihydroxysilane 28, which was transformed into the unsaturated L‐xylo‐mesylate 29 and further into the L‐lyxo‐alcohol 30, the mesylate 31, and the L‐xylo‐azide 32. The derivatives 29–31 prefer a sickle zig‐zag and 32 mainly an extended zig‐zag conformation (Fig. 2). The piperidinecarboxylate 15 was obtained from 32 by ozonolysis (→ 33), intramolecular reductive animation (→ 34), and deprotection, while reductive animation of 34 with glycolaldehyde (→ 35) and deprotection gave 16 (Scheme 2). An intramolecular azide‐olefin cycloaddition of 32 yielded exclusively the fused dihydrotriazole 36, while the lactone 39 did not cyclize (Scheme 3). Treatment of 36 with AcOH (→ 37) followed by hydrolysis (→ 38) and deprotection led to the amino acid 18. To prepare the (hydroxymethyl)piperidinecarboxylates 12 and 17, 32 was first dihydroxylated (Scheme 4). The L‐gluco‐diol 40 was obtained as the major product, in agreement with Kishi's rule. Silylation of 40 (→ 42), oxidation with periodinane (→ 44), and reductive animation gave the L‐gluco‐piperidine 45. It was, on the one hand, deprotected to the amino acid 12 and, on the other hand, N‐phenylated (→ 46) and deprotected to 17. While 45 and 12 adopt a 2C5 conformation, the analogous N‐Ph derivatives 46 and 17 adopt a 5C2 and a B3,6 conformation, respectively, on account of the allylic 1,3‐strain. The conformational effects of this 1,3‐strain are also evident in the carbamate 47, obtained from 45 (Scheme 5), and in the C(2)‐epimerized bicyclic ether 48, which was formed upon treatment of 47 with (diethylamino)sulfur trifluoride (DAST). Fluorination of 40 with DAST (→ 49) followed by treatment with AcOH led to the D‐ido‐fluorohydrin 50. Oxidation of 50 (→ 51) followed by a Staudinger reaction and reduction with NaBH3CN afforded the (fluoromethyl)piperidine 52, while reductive amination of 51 with H2/Pd led to the methylpiperidine 55, which was similarly obtained from the keto tosylate 54 and from the dihydrotriazole 36. Deprotection of 52 and 55 gave the amino acids 13 and 14, respectively. The aniline 17 does not inhibit V. cholerae sialidase; the piperidines 12–16 and 18 are weak inhibitors, evidencing the importance of an intact 1,2,3‐trihydroxypropyl side chain.
Imidazole‐Analogues of 6‐Epicastanospermine and of 3,7a‐Diepialexine
Authors: Frankowski Andrzej , Seliga Czeslawa , Bur Daniel , Streith Jacques
Published: December 2004

The chiral bicyclic imidazol derivatives 7 and 8 were obtained from D‐glucose derivative 9 by a sequence of selective protection/deprotection and intramolecular SN2 reactions. Triols 7 and 8 are analogues of 6‐epica‐stanospermine (4) and of 3,7a‐diepialexine (6), respectively, and are potential glycosidase inhibitors. However, their anti‐HIV activity proved to be only marginal.
Regioselectivity, Stereoselectivity, and Isotopically Sensitive Branching in the Fe(I)‐Mediated Dehydrogenation of Octane‐1,8‐diol in the Gas Phase
Authors: Prüsse Tilmann , Fiedler Andreas , Schwarz Helmut
Published: December 2004

Regio‐ and stereospecific labeling experiments are conducted to unravel the mechanistic features of the Fe+‐induced dehydrogenation of octane‐1,8‐diol in the gas phase. With regard to the regioselectivity, ca. 20% of molecular hydrogen originates from the C(3)/C(4) or the equivalent C(5)/C(6) positions. The remaining 80% are, provided by the C(4)/C(5) methylene units. The steps, preceding the reductive elimination of hydrogen, are irreversible, and the overall reaction follows a 1,2‐elimination mode. The loss of HD from C(3)/C(4) is associated with a kinetic isotope effect K/KHD = 1.68. Formation of D2 from the positions C(4)/C(5) has an isotope effect of K/K = 4.7; this figure is slightly dependent on the configuration at C(4)/C(5). Most interesting is the finding that the configuration at C(4)/C(5) in [4,5‐D2]octane‐1,8‐diol, i.e. 5c vs. 5d, plays a pivotal role in the dehydrogenation of the central C(4)/C(5) part. This unexpected and unprecedented result is explained in terms of conformational analysis. A staggered‐like conformation serves as a precursor to generate a trans‐fused bicyclic intermediate 6. It is this very intermediate from which most of the molecular hydrogen is eliminated. Of minor importance is the as‐fused chelate 7, which is formed from an eclipsed‐like conformation of the octane‐1,8‐diol/Fe+ complex. The contribution of 6 and 7 to the product formation is controlled by the relative configuration at the labeled positions C(4)/C(5). For the D,L‐form 5c, we estimate a ratio of ca. 9:1 for the contribution of 6 vs. 7; due to an isotope effect, this ratio drops to 1:85:1 for the meso‐form 5d. This finding constitutes the first example for the existence of isotopically sensitive branching (‘metabolic switching’) in gas‐phase organometallic chemistry.