Inhaltsstoffe des Osmanthus-Absolues. 4. Mitteilung: Megastigma-5, 7 (E), 9-trien-4-on und Megastigma-5, 8 (E)-dien-4-on

Constituents of Osmanthus Absolute, 4th Communication. Megastigma-5, 7 (E), 9-triene-4-one and Megastigma-5, 8 (E)-diene-4-one In continuation of our communications on constituents of Osmanthus absolute, we now report on the occurrence of the two title compounds 1 and 2a in this natural substrate (0.01-0.02% each). Their structures were confirmed by synthesis starting from β-ionone via the common intermediate 4-oxo-β-ionol ( 9 ). Some further minor components bearing corresponding structural features are tabulated in view of possible biogenetic pathways leading to 1 or 2a , respectively. In order to clarify the olfactory behaviour, we also synthesized some analogous derivatives in the irone series, these substances being not yet found in nature.     

Inhaltsstoffe des Osmanthus-Absolues 6. Mitteilung. (7S, 10S, 5E)- und (7R, 10S, 5E)-2,6,10-Trimethyl-7,10-epoxy-2,5,11-dodecatrien

Constituents of Osmanthus Absolute, 6th Communication. (7 S , 10 S , 5 E ) - and (7 R , 10 S , 5 E )-2,6,10-Trimethyl-7,10-epoxy-2,5,11-dodecatriene Two novel sesquiterpenoid oxides 1a and 1b from Osmanthus absolute have been identified. Their structural proof is based on pectral data and synthesis starting from the known methyl [5-methyl-5-vinyl-tetrahydrofur-1-yl] ketones ( 4a and 4b , respectively), whose configuration is well established. The thus obtained compounds 1a / 1b identical with the natural products, were accompanied by their corresponding 6-methylidene isomers 3a and 3b which could not be detected in the natural substrate.     

Inhaltsstoffe des Osmanthus-Absolues. 1. Mitteilung: 2,5-Epoxy-megastigma-6,8-dien

Constituents of Osmanthus Absolute, Ist communication:2,5-Epoxy-megastigma-6,8-dienes Besides some further ionone derivatives we identified two new bicyclic oxacompounds ( 1a / 1b ) of the megastigmane type in the Osmanthus absolute. Isolation, special features of their spectral datas and synthesis starting from ethyl α-safranate are described. The synthetic pathway choosen allowed the additional identification of four substances occurring in the same natural substrate, because some synthetic by-products formed int he reaction sequence exhibited corresponding spectra and GLC. retention as the hitherto unknown components of the Osmanthus absolute.     

Inhaltsstoffe des Osmanthus-Absolues. 2. Mitteilung: 2,7-Epoxy-megastigma-4,8(E)-dien

Constituents of Osmanthus Absolute, 2nd communication: 2,7-Epoxy-megastigma-4,8 (E)-diene The characteristic fragmentation pattern in the mass spectrum of 2,7-epoxy-dihydro-α-ionone bearing a new oxabridged ionone skeleton has lead to the identification of a further trace component in Osmanthus absolute, the 2,7-epoxy-megastigma-4,8(E)-diene. The synthesis was performed in three steps starting from the above mentioned new ionone derivative now synthetically available by base treatment of 2-hydroxy-α-ionone [1].     

Synthesis of 8-demethyl-8-hydroxy-5-deazariboflavins

1-Deoxy 1-(3,4-dihydro-8-hydroxy-2,4-dioxopyrimido[4,5-b]quinolin-10-(2H)-yl)-D-ribitol (7,8-didemethyl-8-hydroxy-5-deazariboflavin), the flavin moiety of Methanobacterium coenzyme F₄₂₀, and its 7-methyl analog were prepared by acid-catalyzed reaction of appropriately substituted 6-(N-D-ribitylanilino)uracils with trimethyl or triethyl orthoformate followed by deprotection.     

Stereoselectivity in Reactions of Metal Complexes IV. Asymmetric Synthesis of (2R, 7S, 10R)- and (2R, 7R, 10R)-2, 10-diamino-5, 5, 7-trimethyl-4, 8-diazaundecanenickel (II) by Stereoselective Hydrogenation of (2R, 10R)-2, 10-diamino-5, 5, 7-trimethyl-4, 8-diaza-7-undecenenickel(II)

The catalytic hydrogenation of (2R, 10R)-2, 10-diamino-5, 5, 7-trimethyl-4, 8-diaza-7-undecenenickel(II) yields two products when the reaction is performed in the presence of ethylenediamine, but only one, when ethylenediamine is absent. The stereochemistry of the reaction is discussed and a proposal for the absolute configuration of the two diastereomeric complexes and the free ligands is given on the base of CD.- and NMR.-spectra.     

Development of a new synthesis of 3-(1H-tetrazol-5-yl)-4(3H)-quinazolinone,sodium salt via an amidine intermediate

A new synthesis of the recently reported 3-(1H-tetrazol-5-yl)-4(3H)-quinazolinone, sodium salt ( 1 , MDL-427), an experimental mediator release inhibitor, was developed from: (1) reaction of 5-aminotetrazole 3 and triethyl orthoformate 6 to give ethyl N-(1H-tetrazol-5-yl)formimidate 8 , (2) reaction of methyl anthranilate and imidate 8 to give amidine 11 , and (3) treatment of 11 with base to give 1 . Investigation of each of these steps independently led to a significantly more efficient, facile and higher-yielding 1-pot process. A brief examination of anthranilic acid 13 and its salts and derivatives 14 to 17 in this process found them to have dissimilar reactivities. The formation of amidine 11 as an isolable intermediate was unusual, as was its failure to cyclize under standard neutral or acidic conditions. The absolute requirement for base to effect cyclization of 11 appears to be unprecedented.     

Inhaltsstoffe des Osmanthus-Absolues. 3. Mitteilung: Derivate der theaspirane

Constituents of Osmanthus-Absolute, 3rd communication: Derivatives of Theaspiranes Four isomeric new 7-oxo-dihydrotheaspiranes were identified in Osmanthus absolute. Their configuration was proved by synthetic correlations with racemic as well as optically active theaspiranes A and B. These two compounds also occurring in the same natural substrate were first correlated with the (?)-theaspirone A of known absolute configuration and the (+)-theaspirone B, respectively, thus giving the background for all further stereochemical relationship work. In depth studies in the ¹H- and ¹³C-NMR.-spectroscopy field including all possible and now synthetically available hydroxy derivatives of the new oxo compounds enabled us to unambiguously assign structures 1 to 4 to the natural products. Some further constituents bearing the same spirocyclic skeleton were also detected in Osmanthus absolute.     

Quinone Imines with a Fused Azine Ring: I. Synthesis and Hydrochlorination of 5-(p-Tolylsulfonylimino)quinolin-8-one

5-(p-Tolylsulfonylimino)quinolin-8-one was synthesized, and its reaction with hydrogen chloride was studied. The reaction leads to formation of 7-chloro-8-hydroxy-5-(p-tolylsulfonylamino)quinoline hydrochloride.     

Reactions of 3-acetyltropolone and its methyl ethers with hydroxylamine. Formation of 8H-cyclohept[d]isoxazol-8-one and 8H-cyclohept[c]isoxazol-8-one

The reaction of 3-acetyltropolone ( 1 ) with hydroxylamine under the acidic condition gave 3-methyl-8H-cyclohept[d]isoxazol-8-one ( 4 ) and its oxime ( 5 ), and under the neutral condition gave 4 and 3-acetyltropolone oxime ( 6 ). The reaction of 3-acetyl-2-methoxytropone ( 2a ) with hydroxylamine under the acidic condition gave 4, 5 , and 4-methyl-1H-2,3-benzoxazin-1-one ( 7 ), and under the neutral condition gave 4, 7 , 3-methyl-8H-cyclohept[c]isoxazol-8-one ( 8 ), and its oxime ( 9 ). The reaction of 7-acetyl-2-methoxytropone ( 2b ) with hydroxylamine under the acidic condition gave 4 and 5 , and under the neutral condition gave 5, 7 , and 9 .     

Synthesis and properties of 7-hydroxy-8-phenylxanthine and its derivatives. Disproportionation to derivatives of 8-phenylxanthine and 6-amino-5-nitrosouracil

8-Phenyl, 8-(p-methoxyphenyl) and 8-(p-chlorophenyl)-7-hydroxyxanthine were synthesized by ring closure of 6-amino-5-nitrosouracil with benzaldehyde, p-methoxybenzaldehyde and p-chlorobenzaldehyde, respectively. The disproportionation of these products to the corresponding 8-phenylxanthines and 6-amino-5-nitrosouracil was studied. The dependence of the rate of the reaction on the various substituents was studied. The disproportionation reaction is inhibited by the polarophilic ethyl acetylenedicarboxylate and enhanced by phosphate.     

Thermochemistry of europium and dithiocarbamate complex Eu(C5H8NS2)3(C12H8N2)

A solid complex Eu(C₅H₈NS₂)₃(C₁₂H₈N₂) has been obtained from reaction of hydrous europium chloride with ammonium pyrrolidinedithiocarbamate (APDC) and 1,10-phenanthroline (o-phen⋅H₂O) in absolute ethanol. IR spectrum of the complex indicated that Eu³⁺ in the complex coordinated with sulfur atoms from the APDC and nitrogen atoms from the o-phen. TG-DTG investigation provided the evidence that the title complex was decomposed into EuS. The enthalpy change of the reaction of formation of the complex in ethanol, Δ_r H _m ^θ(l), as –22.214±0.081 kJ mol^–1, and the molar heat capacity of the complex, c _m, as 61.676±0.651 J mol^–1 K^–1, at 298.15 K were determined by an RD-496 III type microcalorimeter. The enthalpy change of the reaction of formation of the complex in solid, Δ_r H _m ^θ(s), was calculated as 54.527±0.314 kJ mol^–1 through a thermochemistry cycle. Based on the thermodynamics and kinetics on the reaction of formation of the complex in ethanol at different temperatures, fundamental parameters, including the activation enthalpy (ΔH _≠ ^θ), the activation entropy (ΔS _≠ ^θ), the activation free energy (ΔG _≠ ^θ), the apparent reaction rate constant (k), the apparent activation energy (E), the pre-exponential constant (A) and the reaction order (n), were obtained. The constant-volume combustion energy of the complex, Δ_c U, was determined as –16937.88±9.79 kJ mol^–1 by an RBC-II type rotating-bomb calorimeter at 298.15 K. Its standard enthalpy of combustion, Δ_c H _m ^θ, and standard enthalpy of formation, Δ_f H _m ^θ, were calculated to be –16953.37±9.79 and –1708.23±10.69 kJ mol^–1, respectively.     

Thermokinetics on the reaction of formation of Dy[(C5H8NS2)3(C12H8N2)]

The enthalpy change of formation of the reaction of hydrous dysprosium chloride with ammonium pyrrolidinedithiocarbamate (APDC) and 1,10-phenanthroline (o-phen•H₂O) in absolute ethanol at 298.15 K has been determined as (-16.12 ± 0.05) kJ•mol^-1 by a microcalormeter. Thermodynamic parameters (the activation enthalpy, the activation entropy and the activation free energy), rate constant and kinetics parameters (the apparent activation energy, the pre-exponential constant and the reaction order) of the reaction have also been calculated. The enthalpy change of the solid-phase reaction at 298.15 K has been obtained as (53.59 ± 0.29) kJ•mol^t-1 by a thermochemistry cycle. The values of the enthalpy change of formation both in liquid-phase and solid-phase reaction indicated that the complex could only be synthesized in liquid-phase reaction.

     

257. New beta-lactam antibiotics. The preparation of 8-beta-phenylacetamidohomoceph-4-em-5-carboxylic acid (1). Modifications of antibiotics. 7

The thiazolidine β-lactam 3 adds acrolein in a Michael type reaction. The resulting 'carbinolamide 4 is converted to 8-β-phenylacetamido-homoceph-4-em-5-carboxylic acid ( 1 ) by previously described methods.     

Total Synthesis of (+)-(8S,13R)-Cyclocelabenzine

An asymmetric synthesis of the spermidine alkaloid (+)-cyclocelabenzine ( 1a ) and its (?)-(13S)-epimer 1b is described using optically active (+)-(3S)-3-amino-3-phenylpropionic acid as the chiral building block. The isoquinolin-1-one fragment 15 was synthesized by a modified Bischler-Napieralski reaction. The relative configuration of the (?)-isomer was determined by an X-ray crystal-structure analysis, which enabled us to determine the absolute configuration of natural (+)- 1a as (8S,13R).     

Synthesis of potential metabolites of the brain imaging agents methyl (1R,2S,3S,5S)-3-(4-Iodophenyl)-8-alkyl-8-azabicyclo[3.2.1]octane-2-carboxylate

The synthesis of potential hydroxy metabolites of the brain imaging agents methyl (1R,2S,3S,5S)-3-(4-iodophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate and methyl (1R,2S,3S,5S)-3-(4-iodophenyl)-8-(3-fluoropropyl)-8-azabicyclo[3.2.1]octane-2-carboxylate are reported. The nitration of iodophenyltropanes 1 or 2 with nitronium tetrafluoroborate afforded the nitro compounds 3 or 4 which were reduced with iron powder to the corresponding amino compounds 5 and 6 . The final hydroxylated products 7 and 8 were obtained via a modified Sandmeyer reaction.     

Synthese und Chiralität von (5R, 6R)-5,6-Dihydro-β, ψ-carotin-5,6-diol, (5R, 6R, 6′R)-5,6-Dihydro-β, ε-carotin-5,6-diol, (5S, 6R)-5,6-Epoxy-5,6-dihydro-β, ψ-carotin und (5S, 6R, 6′R)-5,6-Epoxy-5,6-dihydro-β,ε-carotin

Synthesis and Chirality of (5R, 6R)-5,6-Dihydro-β, ψ-carotene-5,6-diol, (5R, 6R, 6′R)-5,6-Dihydro-β, ε-carotene-5,6-diol, (5S, 6R)-5,6-Epoxy-5,6-dihydro-β,ψ-carotene and (5S, 6R, 6′R)-5,6-Epoxy-5,6-dihydro-β,ε-carotene Wittig-condensation of optically active azafrinal ( 1 ) with the phosphoranes 3 and 6 derived from all-(E)-ψ-ionol ( 2 ) and (+)-(R)-α-ionol ( 5 ) leads to the crystalline and optically active carotenoid diols 4 and 7 , respectively. The latter behave much more like carotene hydrocarbons despite the presence of two hydroxylfunctions. Conversion to the optically active epoxides 8 and 9 , respectively, is smoothly achieved by reaction with the sulfurane reagent of Martin [3]. These syntheses establish the absolute configurations of the title compounds since that of azafrin is known [2].     

Absolute Conformation and Configuration of (2S, 3S)-3-Acetoxy-5-(dimethylaminoethyl)-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one Chloride (Dilthiazem Hydrochloride)

Resolution of racemic cis-3-(2-aminophenylthio)-2-hydroxy-3-(4-methoxyphenyl) propionic acid ( 2 ) via the cinchonidine salt 3 , and brucine salt 4 , isolation of the calcium salts (+)- and (?)- 5 , as well as their cyclization to enantiomeric 1,5-benzothiazepines (+)- and (?)- 1 , are described. X-Ray single-crystal analysis reveals (2S, 3S) absolute configuration of (+)- 1 on the basis of tentative comparison of CD data with those for the 1,4-benzodiazepine derivative (+)- 8 of known absolute configuration.     

Thermochemistry of the ternary solid complex Gd(C5H8NS2)3(C12H8N2)

The novel ternary solid complex Gd(C₅H₈NS₂)₃(C₁₂H₈N₂) has been obtained from the reaction of hydrous gadolinium chloride, ammonium pyrrolidinedithiocarbamate (APDC), and 1,10-phenanthroline (o-phen · H₂O) in absolute ethanol. The complex was described by an elemental analysis, TG-DTG, and an IR spectrum. The enthalpy change of the complex formation reaction from a solution of the reagents, Δ_r H _m ^ϑ (sol), and the molar heat capacity of the complex, c _m , were determined as being − 15.174 ± 0.053 kJ/mol and 72.377 ± 0.636 J/(mol K) at 298.15 K by using an RD496-III heat conduction microcalorimeter. The enthalpy change of a complex formation from the reaction of the reagents in a solid phase, Δ_r H _m ^ϑ (s), was calculated as being 52.703 ± 0.304 kJ/mol on the basis of an appropriate thermochemical cycle and other auxiliary thermodynamic data. The thermodynamics of the formation reaction of the complex was investigated by the reaction in solution. Fundamental parameters, the activation enthalpy (ΔH _≠ ^ϑ ), the activation entropy (ΔS _≠ ^ϑ ), the activation free energy (ΔG _≠ ^ϑ ), the apparent reaction rate constant (k), the apparent activation energy (E), the preexponential constant (A), and the reaction order (n), were obtained by the combination of the thermochemical data of the reaction and kinetic equations, with the data of thermokinetic experiments. The constant-volume combustion energy of the complex, Δ_c U, was determined as being −17588.79 ± 8.62 kJ/mol by an RBC-II type rotatingbomb calorimeter at 298.15 K. Its standard enthalpy of combustion, Δ_c H _m ^ϑ , and standard enthalpy of formation, Δ_f H _m ^ϑ , were calculated to be −17604.28 ± 8.62 and −282.43 ± 9.58 kJ/mol, respectively. The text was submitted by the authors in English.     

Beiträge zur Chemie des Arsens. 5. Zur Existenz von Penta-tert-butyl-cyclopentaarsan, (t-BuAs)5

Contributions to the Chemistry of Arsenic. 5. On the Existence of Penta-tert-butyl-cyclo-pentaarsane, (t-BuAs)₅ The reaction of tert-butyldichlorarsane with magnesium in tetrahydrofurane or diethylether yields the hitherto unknown penta-tert-butyl-cyclopentaarsane, (t-BuAs)₅ ( 1 ), in addition to the cycloarsanes (t-BuAs)₄ and t-Bu₆As₈. Compound 1 was preparatively concentrated to ? 80 mole-% and characterized by its ¹H-NMR and mass spectrum. The thermodynamic stability of the tert-butyl substituted monocyclic arsanes decreases in the order (t-BuAs)₄ > (t-BuAs)₅ > (t-BuAs)₃. By thermolysis of 1 t-Bu₆As₈ and other polycyclic arsanes are formed.