Seven-membered Cyclic Amines Research Articles

Synthesis and Cholinesterase Inhibitory Potency of 2,3-Indolo-oleanolic Acid and Some Related Derivatives

In this study, the synthesis and biological activities of previously and newly synthesized oleanolic acid derivatives containing seven-membered cyclic amines at the C28 position were described. The obtained compounds were fully characterized via 1H and 13C NMR spectroscopy, and the bioactivity was evaluated by Ellman’s method. Among the tested compounds, 2,3-indolo-oleanolic acid was found to be the most active compound with an IC50 value of 0.78 µM against acetylcholinesterase. These results are significant due to the fact that research on the inhibition of acetylcholinesterase and butyrylcholinesterase enzymes by oleanolic acid, in particular indoloderivatives, is limited.

Asymmetric Hydrogenation of Dibenzo[c,e]azepine Derivatives with Chiral Cationic Ruthenium Diamine Catalysts.

An efficient Ru-catalyzed asymmetric hydrogenation of dibenzo[c,e]azepines is reported. A series of seven-membered cyclic amines were obtained with moderate to excellent enantioselectivity. The catalyst counteranion played an important role in achieving high-level chiral induction. Moreover, a one-pot synthesis of chiral 6,7-dihydro-5H-dibenz[c,e]azepines via two-step reductive amination was also developed.

Rhodium-Catalyzed Asymmetric Synthesis of Seven-Membered Cyclic Amines

Key words rhodium catalysis - enantioselectivity - hydrogenation - cyclic amines

Diastereoselectivity of Azido-Ugi Reaction with Secondary Amines. Stereoselective Synthesis of Tetrazole Derivatives.

The diastereoselectivity of azido-Ugi reaction with cyclic amines was investigated. It was found that the reaction with α-substituted five- to seven-membered cyclic amines proceeds very efficiently to provide high control of diastereoselectivity (≤100% de) under mild conditions. Target tetrazole-derived products were isolated in excellent yields (≤98%). The reaction has a broad scope in terms of its amine, aldehyde, and isocyanide nature. It was found that the diastereoselectivity of the reaction depends on the ring size of the starting cyclic amines. More rigid piperidines provided the highest selectivity of the reaction. Using benzyl isocyanide, the prepared N-benzyl tetrazoles can be deprotected by hydrogenolysis to form the corresponding NH tetrazoles in high yields.

Zirconium-catalyzed desymmetrization of aminodialkenes and aminodialkynes through enantioselective hydroamination.

The catalytic addition of alkenes and amines (hydroamination) typically provides α- or β-amino stereocenters directly through C-N or C-H bond formation. Alternatively, desymmetrization reactions of symmetrical aminodialkenes or aminodialkynes provide access to stereogenic centers with the position controlled by the substrate's structure. In the present study of an enantioselective zirconium-catalyzed hydroamination, stereocenters resulting from C-N bond formation and desymmetrization of a prochiral quaternary center are independently controlled by the catalyst and reaction conditions. Using a single catalyst, the method provides selective access to either diastereomer of optically enriched five-, six-, and seven-membered cyclic amines from aminodialkenes and enantioselective synthesis of five-, six-, and seven-membered cyclic imines from aminodialkynes. Experiments on hydroamination of aminodialkenes testing the effects of the catalyst:substrate ratio, the absolute concentration of the catalyst, and the absolute initial concentration of the primary amine substrate show that the latter parameter strongly influences the stereoselectivity of the desymmetrization process, whereas the absolute configuration of the α-amino stereocenter generated by C-N bond formation is not affected by these parameters. Interestingly, isotopic substitution (H2NR vs D2NR) of the substrate enhances the stereoselectivity of the enantioselective and diastereoselective processes in aminodialkene cyclization and the peripheral stereocenter in aminodialkyne desymmetrization/cyclization.

Synthesis and cytotoxicity of triterpenoid seven members cyclic amines

Synthesis of 3-deoxy-3a-homo-3a-aza-derivatives of betulin and erythrodiol from betulonic and oleanonic acids was carried out. The most antineoplastic activity with a wide range of action at in vitro testing showed 3-deoxy-3a-homo-3a-aza-28-hydroxy-12(13)-oleanene, which by results of profound studying could be recommended for in vivo investigation. Its modification in the C28 position by introduction of amethoxycinnamoyl fragment led to a loss of antineoplastic activity. 3-Deoxy-3a-homo-3a-aza-derivatives of betulin (3-(aminopropyl)-, 28-(2-carboxyethyl)carboxy-, and 28-cinnamoyloxy-) showed moderate antineoplastic activity in the case of Colon Cancer, Breast Cancer and Leukemia cell lines.

Synthesis of Tetrazole-Derived Organocatalysts via Azido-Ugi Reaction with Cyclic Ketimines

A new route to tetrazole-derived cyclic amines based on the TMSN3-modified Ugi reaction with 2-substituted cyclic imines was elaborated. The reaction allows the direct preparation of five-, six-, and seven-membered cyclic amines substituted with a tetrazole ring, which are important types of organocatalysts. The scope and limitations of this method are discussed. In the case of the Ugi reaction with benzyl isocyanide, the N-substituted tetrazoles can be easily debenzylated under catalytic hydrogenation conditions to form NH-tetrazoles in quantitative yields. It was demonstrated that both enantiomers of tetrazole-derived cyclic amines can be prepared by resolution with tartaric acid, thereby initiating a simple route to chiral derivatives. One of the obtained chiral tetrazoles was efficiently used as an organocatalyst in the amination reaction.

Formation of Optically Pure Cyclic Amines by Intramolecular Conjugate Displacement

Intramolecular conjugate displacement (ICD) has been applied to the Morita-Baylis-Hillman adducts formed from (5S)-5-(l-menthyloxy)-2(5H)-furanone and aldehydes that carry a protected β- or γ-amino group. DIBAL-H reduction of the resulting ICD products releases optically pure six- or seven-membered cyclic amines having a stereogenic center α to nitrogen.

An Efficient Synthesis of Nitrogen Heterocycles by Cp*Ir-Catalyzed N-Cycloalkylation of Primary Amines with Diols

A new efficient method for the N-cycloalkylation of primary amines with diols catalyzed by a Cp*Ir complex have been developed. A variety of five-, six-, and seven-membered cyclic amines are synthesized in good to excellent yields in environmentally benign and atom economical manner with the formation of only water as a coproduct. A large scale synthesis of N-benzylpiperidine and a two-step asymmetric synthesis of (S)-2-phenylpiperidine using (R)-1-phenylethylamine as a starting primary amine have been also achieved.

CpIr complex-catalyzed N-heterocyclization of primary amines with diols: a new catalytic system for environmentally benign synthesis of cyclic amines.

[reaction: see text] A new efficient method for the N-heterocyclization of primary amines with diols catalyzed by a CpIr complex was developed. A variety of five-, six-, and seven-membered cyclic amines were synthesized in good to excellent yields with the formation of only water as a byproduct. A two-step asymmetric synthesis of (S)-2-phenylpiperidine was also achieved using (R)-1-phenylethylamine as a starting primary amine.

Reaction of Cyclohexa-1,2,3-triene with N,a-Diphenylnitrone: Formation of Seven-membered Cyclic Amines via Piradone Derivatives

Reaction of Cyclohexa-1,2,3-triene with N,a-Diphenylnitrone: Formation of Seven-membered Cyclic Amines via Piradone Derivatives