Nonane Derivatives Research Articles

An Efficient Enantioselective Entry to the Piperidino-Quinolizidine Ring System of Lupine Alkaloids by Means of N-Acyliminium Ion Initiated Cyclization Reactions

An efficient methodology for the enantioselective synthesis of the decahydro-1,5-methano-pyrido[1,2-a][1,5]diazocine skeleton found in tricyclic lupine alkaloids is described, starting from 3,5-disubstituted piperidines as chiral building blocks. Alkyne- or vinylsilane-terminated N-acyliminium ion cyclizations performed on appropriate 3,7-diazabicyclo[3.3.1]nonane derivatives allow for the highly stereoselective construction of piperidino-quinolizidine ring systems. A preliminary application of this methodology results in the synthesis of the quinolizidine alkaloid virgilidone.

ChemInform Abstract: 1H NMR Spectral Study of Some 4‐Hydroxy‐2,6‐diphenylpiperidines and a Systematic Analysis of 1H Chemical Shifts in Some Piperidines and 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 100 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.

3-Azabicyclo[3.3.1]nonane Derivatives: III. Synthesis of 3-Substituted 9-Acetonyl-1,5-dinitro-3-azabicyclo[3.3.1]-non-6-en-8-ones by Mannich Condensation of the Janovsky σ-Adduct of 2,4-Dinitrophenol with Acetonide Ion

A number of 9-acetonyl-1,5-dinitro-3-azabicyclo[3.3.1]non-6-en-8-one derivatives were synthesized by Mannich condensation of 3-acetonyl-2,4-bis(aci-nitro)cyclohex-5-en-1-one disodium salt with formaldehyde and primary amines.

3-Azabicyclo(3.3.1)nonane Derivatives: IV. * Synthesis of Amino Acids with 3-Azabicyclo(3.3.1)nonane Fragment **

A series of 1.5-dinitro-3-azabicyclo[3.3.1]non-6-enes was prepared by reduction of 1-R-2,4- and 1-R-3,5-dinitrobenzenes with potassium borohydride followed by Mannich reaction with formaldehyde and amino acids. The molecular structure of (6-bromo-1,5-dinitro-3-azabicyclo[3.3.1]non-6-en-3-yl)acetic acid was studied by X-ray diffraction analysis. The mechanism of decomposition under electron impact was determined for (7-methoxy-1,5-dinitro-3-azabicyclo[3.3.1]non-6-en-3-yl)acetic acid.

Synthesis of the optically active bicyclo[4.3.0]nonane derivative, regarded as the CD ring moiety of 12-oxygenated steroids

The optically active bicyclo[4.3.0]nonane derivative, considered to be the CD ring moiety of 12-oxygenated steroids was synthesized in the present study, which involved stereo-controlled formation of bicyclo[2.2.2]octane derivative by sequential Michael reaction, formation of tricyclo[5.2.2.0 2,6]undecane derivative by intramolecular pinacol coupling reaction and the CC bond cleavage by retro-aldol reaction.

Synthesis of 6,8-diazabicyclo

[formula: see text] Starting with the proteinogenic amino acid (S)-glutamate, a general method for the synthesis of 3-(piperazin-2-yl)propionic acid esters 7 with various substituents at N-4 of the piperazine ring system is presented. An intramolecular ester condensation of 7 is the key step in the formation of the 6,8-diazabicyclo[3.2.2]nonane derivatives 8-10, which are of interest as conformationally restricted piperazines.

The thermolytic behaviour of hexa-1,5-diene-units incorporated in a stellane and twistbrendane skeleton. A quest for a stepwise Cope rearrangement

The thermolytic behaviour of the tricyclo[3.3.0.03,7]octane (stellane) derivatives 11–13 as well as the tricyclo[4.3.0.03,8]nonane (twistbrendane) derivatives 14 and 15 have been investigated in d8-toluene. All five compounds undergo Cope rearrangements to the tricyclic systems 16–20. By means of 1H NMR spectroscopy the kinetics of these reactions have been studied at different temperatures. The lowest activation energies were encountered for the reactions of 12 and 13 (27.0 and 26.3 kcal mol−1, respectively). Model calculations on the RHF and CASSCF level and beyond (CASPT2N/6-31G*//RHF/6-31G*; CASPT2N/6-31G*//CASSCF/6-31G*) were performed for the rearrangements of 11→16, 13→18, and 27→28. These calculations reveal that the activation energies for the two-step pathway and the concerted pathway are very similar. In the case of 11 and 27 the two step mechanism via a bisallylic diradical intermediate is predicted to be slightly preferred.

An efficient chemoenzymatic access to chiral 3,7-diazabicyclo[3.3.1]nonane derivatives

Enantiopure 3,7-diazabicyclo[3.3.1]nonane derivatives 4 and 5, potential precursors of quinolizidine alkaloids, were synthesised in high yields, starting from the biocatalytic asymmetrization of σ-symmetric 3,5-disubstituted piperidines. Their application to the total synthesis of the new pharmacologically active compounds 3 are also described.

Spectroscopic and Theoretical Investigations of Bicyclic Dioximes and Dimethoximes with Eight-Membered Rings

The bicyclic dioximes 4–6 and dimethoximes 7–9, which contain the functional groups in opposite positions of bridged eight-membered rings, were synthesized. Their conformational properties and transannular interactions were investigated by spectroscopic (PE, 13C NMR) and theoretical (MMX, AM1, ab initio HF, and B3LYP) methods. While in the 3,7-disubstituted bicyclo[3.3.1]nonane derivatives 5 and 8 the eight-membered ring has a CC conformation favourable for through-space interactions of the π(CN) orbitals, in the bicyclo[3.3.0]octane derivatives 4 and 7 as well as the 2,6-disubstituted bicyclo[3.3.1]nonanes 6 and 9 the functional groups are in geometric orientations that are unfavourable for such interactions. Through-space orbital interactions in the molecules with favourable conformations lead to a splitting of the π(CN) MOs of 0.4–0.6 eV.

A Concise and Stereospecific One-Shot Synthesis of Bicyclo[3.3.1]nonenols from Dimethyl 1,3-Acetonedicarboxylate and Enals via the Sequential Michael Addition−Intramolecular Aldolization

The reactions of dimethyl 1,3-acetonedicarboxylate 1 with enals 2 proceeded very smoothly in the presence of a catalytic amount of tetrabutylammonium fluoride or piperidine in THF at room temperature, giving the corresponding bicyclo[3.3.1]nonane derivatives 3 in high yields. Both of the two fused rings of 3 are newly constructed from the starting two acyclic substrates via the sequential Michael addition−intramolecular aldolization in one shot.

ChemInform Abstract: Stereocontrolled Preparation of cis‐ and trans‐2,6‐Dialkylpiperidines via Diastereoselective Reaction of 1‐Aza‐4‐oxabicyclo[4.3.0]nonane Derivatives with Grignard Reagents.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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.

Total synthesis of (±)-quinolizidine 207I, an alkaloid from Mantella baroni, a Madagascan mantelline frog

The first synthesis of quinolizidine 207I was achieved by a totally stereocontrolled approach starting from a 9-azabicyclo[3.3.1]nonane derivative, thus establishing the exceptional axial stereochemistry of the ethyl group at position 1.

Stereocontrolled preparation of cis- and rans-2,6-dialkylpiperidines via diastereoselective reaction of 1-aza-4-oxabicyclo[4.3.0]nonane derivatives with Grignard reagents

We report here the syntheses of cis- and trans-2,6-disubstituted piperidines using chiral 1-aza-4-oxabicyclo[4.3.0]nonane synthon 1, which shows high reactivity toward nucleophilic attack at its C-5 position. Bicyclic compounds resembling synthon 1 were transformed to cis- and trans-2,6-disubstituted piperidine derivatives via reactions with various Grignard reagents in a stereospecific manner. Using this methodology, (+)-solenopsin A ( 2b) and both enantiomers of isosolenopsin A ( 3a and 3b) were synthesized in an enantioselective manner from a single enantiomeric source.

Quantitative determination of conformational equilibria in 3,7-diazabicyclo[3.3.1]nonane derivatives

A method of quantitative determination of a conformational equilibrium in 3,7-diazabicyclo[3.3.1]nonane (bispidine) derivatives is described. It is based on a comparison of coupling constants J 1−2 β and others with the corresponding ones from the models of pure conformers. 3-Benzyl-7-methyl-3,7-diazabicyclo[3.3.1]-nonane ( 4) proved to exist mainly in a double-chair (CC) conformer, although there is also a significant contribution of chair-boat (CB) and boat-chair (BC) conformers. In 3-benzyl-7-methyl-3,7-diazabicyclo[3.3.1]nonan-9-one ( 5), a CB conformer predominates over significant amounts of BC and CC.

ChemInform Abstract: Structural Study of 3‐Azabicyclo[3.3.1]nonane Derivatives Functionalized at 1 and/or 9‐Positions by Molecular Mechanics Calculations and NMR Spectroscopy.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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, Pharmacological Characterization, and Quantitative Structure−Activity Relationship Analyses of 3,7,9,9-Tetraalkylbispidines: Derivatives with Specific Bradycardic Activity

A series of 3,7,9,9-tetraalkyl-3,7-diazabicyclo[3.3.1]nonane derivatives (bispidines) was synthesized and identified as potential antiischemic agents. Pharmacological experiments in vitro as well as in vivo are described, and the results are listed. For selection of those compounds fitting best to the desired profile of a specific bradycardic antianginal agent--decrease in heart rate without affecting contractility and blood pressure--these results were scored and ranked. Quantitative structure--activity relationship (QSAR) analyses were performed and discussed a posteriori by means of Hansch, nonelementary discriminant and factor analysis to get insight into the molecular features determining the biological profile. Highly significant equations were obtained, indicating hydrophobic and steric effects. Both pharmacological ranking and QSAR considerations showed compound 6 as the optimum within the structural class under investigation. Compound 6 (tedisamil, KC8857) has been selected as the most promising compound and was chosen for further pharmacological and clinical investigations as an antiischemic drug.

Condensation of 5-aminothieno[2,3-c]pyridazine-6-carbaldehyde with aliphatic primary amines. Synthesis of new heterocyclic 2,6,9-triazabicyclo[3.3.1]nonane derivatives

5-Amino-3,4-diphenylthieno[2,3-c]pyridazine-6-carbaldehyde (2) undergoes condensation with aliphatic primary amines to give the corresponding 2,6,9-triazabicyclo[3.3.1]nonane derivatives 1 with different substituents at position 14. The molecular and crystal structure of 1b (R = Bu) have been determined by X-ray analysis. A suitable mechanism for the formation of 1 is proposed.

Nitropyrimidinones; Synthetic Equivalents of Diformylamine and Nitromalonaldehyde

Reactions of two isomeric nitropyrimidinones with bidentate enolate anions were studied. When 3-methyl-5-nitropyrimidin-4(3H)-one (1) was employed, ring transformation proceeded to give pyridin-4(1H)-ones 3 functionalized at the 3- or 5-positions. This pyrimidin-4-one 1 behaved as an activated diformylamine HN(CHO)2. 1-Methyl-5-nitropyrimidin-2(1H)-one (2) afforded polyfunctionalized bicyclo[3.3.1]nonene derivatives 7 and 8 and/or p-nitrophenol derivatives 9. In this case, pyrimidin-2-one 2 acted as the synthetic equivalent of unstable O2NCH(CHO)2. These two nitropyrimidinones are valuable intermediates for the synthesis of polyfunctionalized compounds.

Elaboration of S-(-)-α-Pinene into Functionalized Bicyclo[4.2.1]nonane Framework of Mediterraneols

A two-carbon ring expansion of (-)- α -pinene 1 to bicyclo[5.1.1]nonane system (+)-12 and 1,2-cationic rearrangement provides an entry into a functionalized bicyclo[4.2.1]nonane derivative, representing the carbocyclic skeleton, present in the novel marine diterpenes, mediterraneols.

Structural study of 3-azabicyclo[3.3.1]nonane derivatives functionalized at 1 and/or 9-positions by molecular mechanics calculations and NMR spectroscopy

Some 3-azabicyclo[3.3.1]nonan-9-ones, 1–3, 1-alkoxycarbonyl derivates, 4,5 and α and β3-methyl-3-azabicyclo[3.3.1]nonan-9-ols, 6, 7, have been studied by means of the molecular mechanics (MMX) method and 1H, 13C-NMR spectroscopy. Experimental data fit well with theoretical calculations. It is found that the conformational behaviour of the bicyclic system is governed mainly by steric factors and a flattened chair-chair conformation bearing the N-substituent in the equatorial position (CC- β) is always preferred. A monoconformational character can be reasonably assumed except for 3-methyl-3-azabicyclo[3.3.1]nonan-9, β-ol, 7, in non polar solvents where the BC- α form should amount to about 15% of the equilibrium mixture.