Perhydroisoindoliniums et perhydroisoquinoliniums: Préparation et étude stéréochimique

By cyclization in aqueous media, 2-aminomethyl 1-alcynyl 1-cyclohexanols lead to perhydroisoindolinium or perhydroisoquinolinium salts. The stereochemistry of isolated diastereoisomers is elucidated. A stereoselectivity favouring trans junction of the rings is pointed out.     

Synthèses stéréosélectives de deux trioxydes C18H30O3 stéréo-isomères,d'ambréinolide et de sclaréol-lactone à partir de dérivés du (+)-manool

Ambreinolide, sclareol-lactone and a pair of new trioxides C₁₈H₃₀O₃ have been synthesized from suitable derivatives of (+)-manool through stereoselective reactions.     

Synthèse et réactivité de dihydrotriazines et de dihydrotriazolotriazines

Generally, 4,5-dihydro-3triazinones have been prepared by a basic hydrolysis of 3-methylmercapto-4,5-dihydrotriazines. Of the serveral methylation methods, namely, diazomethane, methyliodide, dimethyl sulfate all in the presence of sodium methylate or silver carbonate, only methyl bromide in the presence of phase transfer catalyst was sucessful in producing all of the N-2 and/or N-4 methylate compounds. Two unequivocal syntheses of dihydrotriazolo[4,3-b]triazine are reported.     

Polymérisation anionique de l'isoprène: Nature de la paire d'ions et stéréospécificité

With accumulated HR-NMR spectra of anionic polyisoprenes, it has been possible to study the influence of the nature of the propagating species on the microstructure of the obtained polymers If free ions are responsible for the propagation, the microstructure (1,4-: 25%, 1,2-: 33%, 3,4-: 42%) does not depend on the nature of the cations. But with contact ion pairs, the different addition modes are governed by the size of the alkali metal counterions. Mechanisms of anionic propagations via diene–cation coordination are proposed.     

Réactions de substitution nucléophile de l'hydroxyurée. Synthèse et étude des oxa-6 dihydrouraciles

Hydroxyurea, an N-protected hydroxylamine, reacts with α-bromoesters to give α-ureidoxyesters. Some of these have been isolated. Their cyclisation is a synthetic route to 6-oxadihydrouraciles which structure has been well established by means of physicochemical methods. Especially, ¹³C nmr spectroscopy has been used to show only the presence of the diketone tautomeric form.     

Synthèse et réactivité de nitro indazoles

Synthese and nmr study of forty-four nitroindazoles in which twentry-three were never published have been carried out. The best way to obtain the halogenomethyl derivatives(halogenation before or after methylation) is shown. Relative reactivities of the different heterocyclic ring positions toward the electrophilic agent are discussed.     

Synthèse et étude physico-chimique de sulfures,sulfoxydes et sulfones en série thiazolique

The alkylation of Δ⁴-thiazoline-2-thiones under phase transfer catalysis conditions leads to the corresponding thioethers in good yields. The oxidation of 2-alkylthiazoles with m-chloroperbenzoic acid leads to the corresponding sulfines or sulfones depending on experimental conditions in yields of about 80-90%. The characteristic gle, tlc, ir, ¹H nmr and ms data are reported for most of the compounds studied.     

Synthèse et étude conformationnelle de dioxa-1,3 aza-9 spiro[5,5]undecanes

Synthesis of the new l,3-dioxa-9-azaspiro[5.5]undecane ring, was realized by the scheme represented in Figure 2. Butyro-phenones 6 posses neuroleptic activity similar to that of halo-peridol. The pharmacological activity was reported in another publication (2). Conformational study of l,3-dioxa-9-azaspiro-[5.5]undecanes shows the existence of four conformations A, B, C and D, which are shown in Figure 4. The existence of these conformations depends on the nature of the substituents R and R' on the dioxane ring. Thus, in the compounds where R ≠ H, R' = H, the four conformations are possible with a preponderance of A and B. If R and R' are different from H only the conformation A is present in 99% concentration. Lastly, when R = R' = H, the four conformations are possible with equal population for the couple A, B and the couple C, D; the first couple predominating. The presence of a fluorophenylbutyric moiety on the piperidine nitrogen does not seem to stereochemically modify the heterocyclic group.     

Synthèses et caractérisation de germylènes difonctionnels

Syntheses and caracterization of bifunctional germylenes Several synthetic methods of bifunctional germylenes GeY₂ (Y = RO, PhO, RS, CH₃COO, Acac; Y₂ = OCH₂CH₂O, SCH₂CH₂S) or GeXY (Y = RO, X = Cl; Y = RS, X = Cl; Y = Acac, X = Cl) such as exchange reactions, dechlorhydratation reactions and nucleophilic substitutions from GeCl₂ · dioxane are described. Some more synthesis of divalent species GeY₂ from Ge(OR)₂ by transalcoxylation and from Ge(Cp)₂ by cleavage using protic species will be presented. The stability and reactivity of these germylenes are discussed. Difunctionnal germylenes give generally a selfpolycondensation reactions. However, their reactivity in situ shows a effective participation of monomeric species GeY₂.     

Le diméthyl- et le diéthyl-tétracarbonylosmium Synthèse et réactivité

The sodium salt Na₂[Os(CO)₄] has been obtained in high yields by the reduction of either OsH₂(CO)₄ or Os₃(CO)₁₂ with sodium sand in the presence of catalytic amounts of 2, 2′-bipyridyle. The reaction of Na₂[Os(CO)₄] with alkylating agents such as methyl and ethyl iodide produces OsR₂(CO)₄ (R = CH₃, C₂H₅). NMR. and IR. spectra indicate a cis-octahedral structure of symmetry C_2v for these new alkyl compounds. Bromine breaks one osmium-carbon bond in cis-Os(CH₃)₂(CO)₄ to give cis-OsCH₃Br(CO)₄, whereas in cis-Os(C₂H₅)₂(CO)₄ both ethyl groups are easily displaced by bromine to give cis-OsBr₂(CO)₄. Under CO pressure and at elevated temperature cis-Os(CH₃)₂(CO)₄ is converted to Os(CO)₅ and ethane. With cis-Os(C₂H₅)₂(CO)₄ two CO are inserted in osmium-carbon bonds to give . NMR. and IR. data suggest a cis-configuration for this derivative and the possibility of the presence of rotational isomers.     

Contribution à l'étude de l'ionisation des films insolubles de polyélectrolytes stéréoréguliers

The surface potentials of monolayers of poly(methacrylic acid) (PMA) have been studied as a function of the pH of the subsolution. The influence of the macromolecular configuration on the properties of the ionizable groups was more particularly investigated. Orientation of molecules in the monolayer may be imposed by the stereoregularity of PMA (isotactic, atactic) and by the nature of the interface (air–water, cyclohexane–water). The results are analyzed in terms of theories of the ionic double layer (Gouy model, Donnan equilibrium) which permit the determination of the degree of ionization α of the film. The value of α gives indications about the orientation of specific groups of the macromolecular chain, i.e., of the ionized monomer units. Indeed, at the air–water interface, the film of isotactic PMA is more acid than that of the atactic sample, and at the cyclohexane–water interface, the degree of ionization is greater than at the air–water interface. These properties are the consequence of a modification of orientation of the hydrophilic groups with respect to the aqueous phase as a function of the stereoregularity of the sample and the nature of the interface. The variation of α with the pH of the substrate phase may be used to calculate an intrinsic dissociation constant K_s° of the molecules in the film. The value of K_s° is not modified by spreading conditions and remains very similar to that obtained in solution.     

Contribution à l'étude de la réaction de Birch en séries isoquinoléique et diaza-8,13 stéroïdique

The hydrogenation of isoquinolines following the Birch procedure was studied. We have found the conditions to obtain di or tetra hydrogenation of the homocycle. This was applied to a derivate of the 8,13-diazaestrone and we can point out the necessity of a piperidine-like amine function. this work led up to the synthesis of 8,13-diaza-19-norandrostane-3-one and 8,13-diaza-19-norandrost-4-ene-3-one with “natural” configuration.     

Synthèse et stéréochimie de perhydrocyclopenta[b]furannones-3-cis et perhydrocyclopenta[b]furannols-3-cis

Synthetic route to new cis-perhydrocyclopenta[b]furan-3-ones and cis-perhydrocyclopenta[b]furan-3-ols is described. Their configurations and conformations were inferred by ¹H and ¹³C nmr spectroscopy. A certain rigidity is associated with the bond common to the two fused ring. The conformation of tetrahydrofuran-3-one ring appears to be a composite of the C, and C₂ forms depending on the C-2 substitution.     

Polymérisation anionique de l'isoprène: Nature de la paire d'ions et stéréospécificité. II. Influence de la nature du solvant

The present work reports some new results on the dependence between the stereospecificity of the anionic propagation of isoprene and the nature of the active centers. The stereospecificity of the propagation of macroheterobicylce separated ion pairs does not depend on the nature of the alkali counterions, and the microstructure of the polyisoprenes obtained does not differ from that of those produced by free ions. Variations in the microstructure were observed in the propagation of contact ion pairs, depending on the nature of the cation and the solvent used. These variations are likely to be related to the degree of intimacy of the contact ion pairs. There are two main factors which affect the stereospecificity of the propagations in different ways: the size of the cation and the donating power of the solvent. Finally, the external solvation of the propagation ions pairs was confirmed by the microstructure of polyisoprenes synthesized in mixed (inert + donor) solvents.     

Synthése,stéréochimie,et réactivité thermique de (N-méthylidenealkylamino)-2 aziridines

1-Alkyl-2-(N-methylidenealkylamino)aziridines are obtained by the reaction of primary amines with either α-chloroacraldehyde or α-chlorocrotonaldehyde. Structural assignments are made by nmr spectroscopy. The thermal rearrangement of 1-alkyl-2-(N-methylidenealkylamino)-3-methylaziridines to pyrroles is described.     

Synthèse et étude de modèles de NADH à noyaux accolés en série pyrrolo[2,3-b] et [3,2-b]pyridines

Pyrrolo[2,3-b] and [3,2-b]pyridines derivatives, precursors for annealated NADH models have been prepared. Several methods for building a pyridinic annealates ring have been used starting from 2- or 3-aminopyrrole. The corresponding dihydropyridine structure leads to highly reactive NADH models compounds and are very much more stable than common models.     

Synthèses d'hétérocycles indoliques à partir de dérivés carbonylés de l'indole et du pyrrole

The reactions of ethyl azidoacetate with 1-methylindole-2-3-dicarboxaldehyde (1) and its monoacetal 2 afforded β and γ carbolines. The regioselectivity of condensation of ethy6l aminoacetate with 1 was investigated and yields a γ-carboline. Derivatives of a new heterocycle, the thiepino[4,5-b]indole and its application of the synthesis of some carbazoles are described.     

Synthèse d'une sonde biotinylée à bras clivable allongé pour l'isolement des récepteurs de l'angiotensine II

Synthesis of a Biotinylated Probe with an Extended Cleavable Arm for Angiotensin II Receptors Purification We have synthesized a new biotinylated probe for angiotensin II receptors studies: biotinyl-NH(CH₂)₂? SS? (CH₂)₂? CO-Gly-? Ahx-[Ala¹, Phe(4N₃)⁸]angiotensin II ( 5 ). This molecule can be photoactivated through an arylazido group. ¹H-NMR studies suggest that it adopts an extended conformation which should allow a simultaneous recognition of both streptavidin and hormone receptor. It has a good affinity for receptors (K_d = 1 nM) and hence is a promising tool in their detection (autoradiography, gold-, ferritin-, enzyme-, or fluorescent streptavidin derivatives) and separation (cell sorting, affinity chromatography). It can be monoiodinated (°6) at its tyrosine residue without a significant loss of affinity. Its extended cleavable arm allows an easy recovery of the ‘probe-receptor’ complex from streptavidin. An HPLC monitoring of the synthesis is described, particularly of the segment coupling 1 + 2 in presence of (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP). This method can be used as well for synthesis of the D -Phe⁸ derivative that has antagonist properties.