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Synthesis of Spyrohydantoines Derivatives of 2,4-Diphenyl-3-azabicyclo[3.3.1]nonane and 7,9-Diphenyl-8-azabicyclo[4.3.1]decane via Bucherer Reaction in N,N-Dimethylformamide: Influence of the Temperature and Stereochemical Path The unreactives ketones related to 2,4-diphenyl-3-azabicyclo [3.3.1]nonan-9-one to the Bucherer reaction in usuals conditions show excellent reactivity in DMF. as unique solvant. The stereochemical paths of these reactions and the synthetic utility of the temperature modification are described.

Based on the data from 1H nmr spectra, the structure and spatial configuration of the ahove mentioned hydantoins are established. In the 3-alkyl-3-azabicyelo[3.3.f ]nonane-9-spiro-5′-hydantoins analyzed, we confirm the chair-chair configuration and the presence of only one stereoisomer at the spiro carbon atom (with the C4′=() group axial with regard to the piperidine ring). In the 3,7-dialkyl-3,7-diazabieyclo[3.3.1 ]nonane-9-spiro-5′-hydantoins analyzed, we also confirm the chair-chair configuration and we calculate the percentage of the two stereoisomers when they exist.

l'alcoylation de la cyclohexanospirohydantoine dans des conditions classiques et en transfert de phase conduit respectivement aux derives N-3-substitues et aux derives N-1,N-3-disubstitues. l'application successive de ces methodes a permis d'acceder facilement aux hydantoines portant deux substituants differents. Les differents produits obtenus ont ete etudies par rmn du 13C. Cette methode permet d'identifier les produits mono- et disubstitues ainsi que de determiner la position du substituant. Usual alkylation conditions or phase transfer alkylation of cyclohexanespirohydantion leads respectively to N-3-substituted derivatives or N-1,N-3-disubstituted dervivations. Successive application of the pervious methods easily gave disubstituted hydantions. The reaction products have been studied by 13C nmr in order to indentify mono and disubstituted derivatives and to determine the substituent position.

N3-Substituted hydantoins have been to undergo lithium aluminum hydride reduction (THF, room temperature, 5 hours) to give 4-hydroxy-2-imidazolidinones in good yields.

Facile synthesis of derivatives of 2,4-diphenyl-3-azabicyclo[3.3.1]nonane and 7,9-diphenyl-8-azabicyclo[4.3.1]decane The facile synthesis of hydantoins, cyanhydrins and aminonitriles derived from 2,4-diphenyl-3-azabicyclo[3.3.1]nonanone and 7,9-diphenyl-8-azabicyclo[4.3.1]decanone is described. Configurations at C(9) or C(10) of the new compounds wth pharmaceutical and synthetical utility is deduced from their spectral properties.

The mass spectra of some N-substituted nortropane and granataninespirohydantoins are compared with those of N-substituted 3-azabicyclo[3.2.1]octane-8-spiro-, 3-azabicyclo[3.3.1]nonane-9-spiro-, 8-azabicyclo-[4.3.1]decane-10-spiro- and 3,7-diazabicyclo[3.3.1]nonane-9-spiro-5′-hydantoins. Mass spectra data of monothio- and dithio-tropanespirohydantoins are also included. Mass fragmentation and structure relationships of these molecules have been established.

New analogues of julandine with different aromatic methoxy- and chloro-substituents have been synthesized. Some features of the. nmr spectra of the final products and lactams are discussed. The conformational structure of the final products was determined.

The inhibitory effects on poly(U)-directed polyphenylalanine synthesis of cryptopleurine and a number of structurally related analogs have been compared in a yeast cell-free system. Results suggest that the quinolidine structure by itself does not promote biological activity, and for an inhibitory effect it must be condensed with a phenanthrene or another related compound such as naphthalene. The results are presented and possible relationships between structure and activity for the compounds emetine, tubolosine, tylophora alkaloids, and various cryptopleurine analogs are considered.

Infrared data of some granatanine-3-spiro-5′-hydantoins and tropane-3-spiro-5′-thiohydantoins revealed the ability of these compounds, to exist as zwitterion structures in the solid state. © 1980., We thank Dr. P. HAFNER for the Raman spectrum of one of the compounds studied.

The conformations of a new series of compounds of the general structure N-alkylgranatanine-3-spiro-5′-hydantoin, synthesized in our laboratory from the corresponding 9-alkyl-9-azabieyclo-[3.3.1 ]nonan-3-ones, were studied by 1 H nmr spectroscopy at different pH values in some instances. We have assigned boat conformations for the spiropiperidines.

N (8)-Ethylnortropane-3-spiro-5′-oxazolidine-2′-4′-dione hydrochloride has been synthesized and its crystal and molecular structures determined by X-ray diffraction. IR, Raman, 1 H NMR and 13 C NMR methods. It is found that the crystalline structure is maintained in D 2 O solution. In D 2 O solution a protonation equilibrium takes place and the percentages of the two isomers are calculated. In order to correlate the results, analogous spectroscopic measurements have also been made for the N -ethylnortropane-3-spiro-5′-oxazolidine-2′,4′-dione, for which a zwitterionic structure is deduced.

L'utilisation d'une matrice factorielle fractionnaire de seulement seize experiences permet d'etudier l'effet de sept facteurs (volume du recipient, concentrations en cyanure et en carbonate d'ammonium, volumes d'eau et d'ethanol, temperature et temps de reaction) sur le rendement en cyclohexane spirohydantoine. La strategie experimentale et les resultats sont compares avec ceux d'une publication recente utilisant la methode d'optimisation du Simplex, montrant une connaissance plus precise de la reaction apres une matrice factorielle. The only sixteen experiments of a fractional factorial design have been necessary to study the influence on the yield of cyclohexanospirohydantoin of the seven following factors: flask volume, cyanide and ammonium carbonate concentrations, quanities of water and ethanol, temperature and reaction time. The experimental strategy and results are compared with a recently published Simplex optimization, showing a better knowledge of the reaction after using a factorial design.

The synthesis of three pharmacologically interesting series of cyclopentane, indene-2 and fluorine-9-spiro-5′-oxazolidine-2′, 4′-dione is described. Based on the data from 1H and 13C nmr spectra, the main conformational features of the above mentioned compounds is established.

The synthesis of the alkaloid cryptopleurine 7b has been accomplished by a sequence involving as a key step the selective Borch reduction of an amidoester 1b to the corresponding aminoester 2b. This route is applicable to the synthesis of derivatives such as 7a.

Some 2- and 3-substituted-1,2,3,4-tetrahydrodibenzo[f,h]isoquinolines were prepared by a synthetic scheme involving a selective Borch reduction of an amide to the corresponding amine and a Friedel-Crafts cyclization to obtain the dibenzo[f,h]isoquinoline system. The title compounds, which have a similarity to the cell growth inhibitory alkaloid cryptopleurine, failed to exhibit significant protein synthesis inhibitory activity.

Based on the data from 1H nmr spectra, the structure and spatial conformation of the N3′-β-dimethyl and diethylaminoethyl derivatives from 3-alkyl-3-azabicyclo[3.2.1]octane-8-spiro-5′-hydantoins and 3-alkyl-3-azabicyclo[3.3.1]nonane-9-spiro-5′-hydantoins are established. The monosubstitution on the imide nitrogen atom has also been confirmed.

The synthesis of 9,10,12,13,14,14a-hexahydrodibenzo[f,h]pyrrolo[2,1-a]isoquinoline 6 has been accomplished by a sequence involving as a key step the Friedel-Crafts intramolecular acylation of the amino acid 9 to the corresponding pentacyclic aminoketone 10. Compounds 7, 11 and 12 showed a significant protein synthesis inhibitory effect.

Some N-substituted bicyclo[3.2.1]octane-3-spiro-3'-pyrrolidine hydrochlorides (IX-XII) prepared from bicyclo[3.2.1]octan-3-one (I), were assayed in vitro against influenza A viruses. All materials showed activity similar to 1-adamantanamine hydrochloride. A 1H-NMR study revealed only one isomer at the spiro carbon atom.

Synthetic methods to prepare N-ω-hydroxyalkyl-nor-psuedopelletierine and granatanine-3-spiro-5'-hydantoin N-ω-hy droxyalkylbenzylic and diphenylacetic esters are analyzed. The Bucherer-Bergs synthesis used by us to obtain some other granatanine-spirohydantoins (2), originates the hydrolysis of the ester group.

The two isomers of 3-aminotropane-3-carboxylic acid have been prepared by hydrolysis of the two α- and β-tropane-3-spiro-5′-hydantoins whose configurations were determined by X-ray crystallography ...

Synthese par 2 methodes a partir de dimethoxy-9,10 hexahydro benzo [a] quinolizinone-2 via les derives cyano-2 cyanomethyl-2 ou cyano-2 [cyano ethoxycarbonyl methyl]-2

The preferred conformations of a pharmacologically interesting series of N-substituted nortropane spirohydantoins were determined from PMR and 13C-NMR data to permit a structure-activity relationship study.

Die nach Schema dargestellte Titelverbindung (V) kristallisiert als Hydrochlorid in der Raumgruppe Pn2 , a mit Z=4 (auch IR, Raman, 1H- und 13C-NMR).

Tropane-3-spiro-4'-imidazol-5'-one has been synthesized and its crystal and molecular structures determined by X-ray diffraction, IR, Raman, 1H-NMR and 13C-NMR methods. The tautomeric equilibrium between this structure and the corresponding conjugated form in different solvents is also studied from IR and UV data. The imidazoline ring, the spiranic C(3, 4'), the N(8) and the methyl C(9) atoms are situated in a plane. The piperidine ring adopts a distorted chair conformation in the crystalline form and in solution. The flattening of the C(1), C(2), C(3, 4'), C(4), C(5) part of the chair and the opposite puckering are noticeably large. In order to complete the results, some spectroscopic measurements have also been made for the tropane-3-spiro-4'-imidazol-5'-one hydrochloride. © 1981., The authors thank the Centro por Proceso de Datos del Ministerio de Educación, Madrid, Spain, for providing facilities for the use of the 1108 Univac computer.

□ A series of N8-alkyloxycarbonylalkyl-nortropane-3-spiro-5′-hydantoins has been synthesized and studied by spectral and crystallographic methods. The crystal and molecular structure of one [8(γ-ethoxycarbonylpropyl)nortropane-3-spiro-5′-hydantoin, VI] was determined by X-ray diffraction. The preferred conformations of these compounds and subsequent changes on protonation were determined from 1H-NMR and 13C-NMR data.

Synthese a partir de chloromethyl-2 naphtalene et de piperidinecarboxylate-2 d'ethyle via la cyclisation intramoleculaire par acylation de Friedel Crafts de l'acide [naphtyl-2methyl-1] piperidinecarboxylique-2. Les donnees spectrales indiquent un conformere trans-condense pour la naptho [1,2-b] quinolizidine

The IR spectra of 3-alkyl-3-azabicyclo(3.2.1)octane-8-spiro-, 3-alkyl-3-azabicyclo(3.3.1) nonane-9-spiro-, and 8-alkyl-8-azabicyclo(4.3.1)decane-10-spiro-5'-hydantoins have been studied in the solid state and in solution and the existence of different types of hydrogen bonding deduced from the spectra. The presence of intermolecular N3'-H⋯N bonds in the solid state depends mainly on the steric hindrance of the polymethylene chain and on the bulk and shape of the piperidine N-substituent. The possibility of strong N3'-H⋯N bond formation is smaller than for isomeric nortropane- and granatanine-spirohydantoins. Results are confirmed in some cases by Raman and X-ray measurements.