Nonane Derivatives Research Articles

ChemInform Abstract: The Mannich Reaction in the Synthesis of N,S‐Containing Heterocycles. Part 8. Aminomethylation of 3,5‐Dicyano‐6‐oxo‐1,4,5,6‐tetrahydropyridine‐2‐thiolates as a Method for the Synthesis of New Functionally Substituted 3,7‐Diazabicyclo[3.3.1]nonane Derivatives.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of bicyclo[3.3.1]nonane derivatives containing fused heterocyclic rings

The condensation reactions of 3,7-dihalobicyclo[3.3.1]nonan-2,6-dione or 3-bromobicyclo[3.3.1]nonan-2one (racemates) with 4-amino-2,4-dihydro-3H-triazolothione, 2-thiobenzimidazole and thiocarbamide were performed. New compounds containing bicyclo[3.3.1]nonane framework with fused thiazole, imidazothiazole and 1,8a-dihydro-5H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine rings were synthesized.

Parallel solid-phase synthesis of novel 3,7-diazabicyclo[3.3.1]nonane derivatives starting from natural alkaloid cytisine

A parallel solid-phase synthesis of combinatorial library of 436 amides of 4-(3,7-diorganyl-3,7-diazabicyclo[3.3.1]nonan-2-yl)butanoic acid has been accomplished starting from natural alcaloid (−)-cytisine. A five-step liquid-phase synthesis resulted in the conversion of cytisine to 7-benzyl-3-[(9H-fluoren-9-yl)methyl]-substituted acids, which were further diversified with the use of solid-phase technology on the acid-susceptible amine resins. The combinatorial library obtained is intended for a discovery of new physiologically active compounds.

Stereospecific Synthesis of Eight-Membered Polyhydroxy Carbocycles via TIBAL-Promoted Claisen Rearrangement

The stereoselective synthesis of novel eight-membered polyhydroxy carbocycles was achieved from d-glucose via mercuriocyclization and triisobutylaluminum (TIBAL)-promoted Claisen rearrangement. Along with rearrangement, TIBAL also promoted debenzylation and cycloaddition, and a 3,9-dioxa-bicy­clo[3.3.1]nonane derivative was formed. The stereoselectivity of mercuriocyclization was attributed to the interaction between me­curio and vinyl moities, and this interaction also assisted the mercurio derivative to exist in an abnormal conformation. The configuration and/or conformation of intermediates and products were identified by NMR spectral analyses.

Design, synthesis and bioactivity of simplified taxol analogues on the basis of bicyclo[3.3.1]nonane derivatives

Four specially designed bicyclo[3.3.1]nonane-based structures were synthesised and found to be cytotoxic at micromolar concentrations and to cause slight non-specific tubulin aggregation.

Novel Azabicyclo[3.2.2]nonane derivatives and their activities against Plasmodium falciparum K 1 and Trypanosoma brucei rhodesiense

New diaryl substituted 2-azabicyclo[3.2.2]nonane derivatives have been synthesized in order to investigate the influence of the aromatic substitution and of N substitution on the antiprotozoal activities of those compounds. Following a manual method for the Hansch approach, different 4-substituted aryl rings were systematically inserted, and moieties with varying basicity and polarity were attached to the ring nitrogen. All compounds were investigated for their activities against Trypanosoma brucei rhodesiense (STIB 900) and the K 1 strain of Plasmodium falciparum (resistant to chloroquine and pyrimethamine) and for their cytotoxicity using microplate assays. Some of the new compounds are amongst the most active antitrypanosomal agents in this series, and the selectivity index of a single derivative is superior in the 2-azabicyclo-nonane series.

The Mechanism of the (Bispidine)copper(II)-Catalyzed Aziridination of Styrene: A Combined Experimental and Theoretical Study

Experimental and DFT-based computational results on the aziridination mechanism and the catalytic activity of (bispidine)copper(I) and -copper(II) complexes are reported and discussed (bispidine=tetra- or pentadentate 3,7-diazabicyclo[3.1.1]nonane derivative with two or three aromatic N donors in addition to the two tertiary amines). There is a correlation between the redox potential of the copper(II/I) couple and the activity of the catalyst. The most active catalyst studied, which has the most positive redox potential among all (bispidine)copper(II) complexes, performs 180 turnovers in 30 min. A detailed hybrid density functional theory (DFT) study provides insight into the structure, spin state, and stability of reactive intermediates and transition states, the oxidation state of the copper center, and the denticity of the nitrene source. Among the possible pathways for the formation of the aziridine product, the stepwise formation of the two N-C bonds is shown to be preferred, which also follows from experimental results. Although the triplet state of the catalytically active copper nitrene is lowest in energy, the two possible spin states of the radical intermediate are practically degenerate, and there is a spin crossover at this stage because the triplet energy barrier to the singlet product is exceedingly high.

Further structural optimization of cis-(6-benzhydryl-piperidin-3-yl)-benzylamine and 1,4-diazabicyclo[3.3.1]nonane derivatives by introducing an exocyclic hydroxyl group: Interaction with dopamine, serotonin, and norepinephrine transporters

Our earlier effort to develop constrained analogues of flexible piperidine derivatives for monoamine transporters led to the development of a series of 3,6-disubstituted piperidine derivatives, and a series of 4,8-disubstituted 1,4-diazabicyclo[3.3.1]nonane derivatives. In further structure–activity relationship (SAR) studies on these constrained derivatives, several novel analogues were developed where an exocyclic hydroxyl group was introduced on the N-alkyl-aryl side chain. All synthesized derivatives were tested for their affinities for the dopamine transporter (DAT), serotonin (5-HT) transporter (SERT), and norepinephrine transporter (NET) in the brain by measuring their potency in inhibiting the uptake of [ 3H]DA, [ 3H]5-HT, and [ 3H]NE, respectively. Compounds were also tested for their binding potency at the DAT by their ability to inhibit binding of [ 3H]WIN 35,428. The results indicated that position of the hydroxyl group on the N-alkyl side chain is important along with the length of the side chain. In general, hydroxyl derivatives derived from more constrained bicyclic diamines exhibited greater selectivity for interaction with DAT compared to the corresponding 3,6-disubstituted diamines. In the current series of molecules, compound 11b with N-propyl side chain with the hydroxyl group attached in the benzylic position was the most potent and selective for DAT ( K i = 8.63 nM; SERT/DAT = 172 and NET/DAT = 48.4).

The Mannich reaction in the synthesis of N,S-containing heterocycles 8. Aminomethylation of 3,5-dicyano-6-oxo-1,4,5,6-tetrahydropyridine-2-thiolates as a method for the synthesis of new functionally substituted 3,7-diazabicyclo[3.3.1]nonane derivatives

Aminomethylation of 3,5-dicyano-6-oxo-1,4,5,6-tetrahydropyridine-2-thiolates upon treatment with primary amines and excess formaldehyde leads to 3,7-diazabicyclo[3.3.1]nonane derivatives. N-Methylmorpholinium 4-(2-chlorophenyl)-3,5-dicyano-6-oxo-1,4,5,6-tetrahydropyridine-2-thiolate was obtained by the reaction of (E)-3-(2-chlorophenyl)-2-cyanoprop-2-enethioamide with 1-cyanoacetyl-3,5-dimethylpyrazole and N-methylmorpholine in acetone in quantitative yield.

Facile synthesis of benzo-fused 2,8-dioxabicyclo[3.3.1]nonane derivatives via a domino Knoevenagel condensation/hetero-Diels–Alder reaction sequence

A facile two-step synthesis of a series of benzo-fused 2,8-dioxabicyclo[3.3.1]nonane derivatives is described, featuring a domino Knoevenagel condensation/intramolecular hetero-Diels–Alder reaction sequence.

Synthesis of adamantane and bicyclo[3.3.1]nonane derivatives with the oxetane moiety

A method of synthesis of 3-hydroxyoxetane esters with adamantane- and bicyclo[3.3.1]nonane-containing carboxylic acids is reported.

Reactions of boron trifluoride with allylic boranes and 1-boraadamantane

The reactions of boron trifluoride with triallyl- and allyldialkylboranes represent a convenient non-catalytic approach to allyl(difluoro)boranes. The rupture of 1-boraadamantane core with BF3 leads to 3-fluoro-7-difluoroborylmethyl-3-borabicyclo-[3.3.1]nonane derivatives.

New 4‐Amino‐2‐azabicyclo[3.2.2]nonane Derivatives and Their Antiprotozoal Potencies.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

A Double Mannich‐Type Reaction in the 1,4,5,6‐Tetrahydropyridine‐2‐thiolate Series: A Convenient Approach to Functionalized 3,7‐Diazabicyclo[3.3.1]nonane Derivatives.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Study of ring cleavage in quaternary ammonium salts of 1,3-diazaadamantane

A series of quaternary ammonium salts of 5,7-dimethyl-1,3-diazaadamantan-6-one bearing aryl and alkyl substituents was synthesized. On treatment with aqueous KOH, these compounds undergo ring cleavage to give 3,7-diazabicyclo[3.3.1]nonane derivatives. The product structure was confirmed by 1H and 13C NMR and IR spectroscopy.

Organocatalyst-Mediated Enantioselective Intramolecular Aldol Reaction Featuring the Rare Combination of Aldehyde as Nucleophile and Ketone as Electrophile

The trifluoroacetic acid salt of 2-(pyrrolidinylmethyl)pyrrolidine was found to be an effective organocatalyst of an asymmetric intramolecular aldol reaction, affording bicyclo[4.3.0]nonane derivatives with a high enantioselectivity, in which the rare combination of aldehyde as a nucleophile and ketone as an electrophile was realized.

A Double Mannich-type Reaction in the 1,4,5,6-Tetrahydropyridine-2-thiolate Series: A Convenient Approach to Functionalized 3,7-Diazabicyclo[3.3.1]nonane Derivatives

The reaction of N-methylmorpholinium 5-alkoxy-carbonyl-4-aryl-3-cyano-2-oxo-1,4,5,6-tetrahydropyridine-2-thiolates with primary amines and formaldehyde under mild conditions afforded 7-substituted alkyl 9-aryl-5-cyano-2-oxo-4-thioxo-3,7-diazabicyclo[3.3.1]nonane-1-carboxylates in fair to good yields (52–74%).

New 4-Amino-2-azabicyclo[3.2.2]nonane Derivatives and their Antiprotozoal Potencies

Several 2-substituted 4-amino-2-azabicyclo [3.2.2]nonane derivatives were synthesized. The new compounds were investigated for their activities against the causative organism of East African sleeping sickness, Trypanosoma b. rhodesiense, and a protozoan parasite which causes Malaria tropica, Plasmodium falciparum K1, a strain which is resistant to chloroquine and pyrimethamine. The results are compared to the activities of 2-unsubstituted 4-amino-2-azabicyclo[3.2.2]nonanes.

Further Studies on Enantioselective Synthesis of (+)‐Anatoxin‐a Using Enyne Metathesis: Unexpected Inversion of Chirality via a Skeletal Rearrangement of 9‐Azabicyclo[4.2.1]nonene Derivatives.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Substituent Effects on the Basicity of 3,7-Diazabicyclo[3.3.1]nonanes

Basicity constants for a series of 3,7-diazabicyclo[3.3.1]nonane derivatives in acetonitrile with a variation over 13 orders of magnitude have been determined using a spectrophotometric titration technique. An excellent correlation between basicity and calculated proton affinities obtained at PCM-B3LYP/6-31+G(d)//B3LYP/6-31G(d) level was found. The results are discussed in terms of substituent effects and compared to (15)N NMR chemical shifts.