Piperidone Ring Research Articles

Remote chiral induction in the thio-Claisen rearrangement of bicyclic thiolactams

A remote steric effect in the bicyclic lactam oxazolidine ring has been shown to affect the stereochemical outcome in the thio-Claisen rearrangement taking place in the piperidone ring.

Nucleophilic Addition of 1-Acetylindole Enolates to Pyridinium Salts. Stereoselective Formal Synthesis of (±)-Geissoschizine and (±)-Akagerine via 1,4-Dihydropyridines

Addition of the enolate derived from 1-acetylindole (3) to pyridinium salt 4b followed by acid-induced cyclization of the resulting 1,4-dihydropyridine 5b in the presence of lithium iodide gives tetracyclic 3,7-methano[1,4]diazonino[1,2-a]indole 6b, which has subsequently been elaborated into the (E)-ethylidene derivative 7b. From this compound is reported a stereocontrolled route to (±)-geissoschizine, involving closure of C ring by Pummerer reaction, methanolysis of the resulting pentacyclic lactam 12, and desulfurization. A similar synthetic sequence starting from the enolate of 3 and 2-fluoropyridinium salt 15b gives access to the pentacyclic dilactam 2, which had previously been converted to (±)-akagerine through opening of the piperidone (D) ring.

δ-valerolactam derivative of C 60 from hetero Diels-Alder reaction with 1,3-bis( tert-butyldimethylsiyloxy)-2-aza-1,3-butadiene

The title 2-aza-1,3-diene reacted smoothly with C 60 at room temperature to give 2-piperidonefused C 60 after hydrolysis A silyoxy group on the piperidone ring was replaced by alkoxy groups by acid-catalyzed substitution reaction with alcohols via an iminium cation intermediate. This type of reaction was applied to reduction by use of triethylsilane to give the parent δ-valerolactam derivative of C 60.

Imidazole derivatives of pyrrolidonic and piperidonic acids as potential inhibitors of human placental aromatase in vitro

Inhibitory activities towards human placental aromatase of novel pyrrolidinone and piperidinone drugs were investigated and compared with those of aminoglutethimide (AG) in vitro. All compounds showing a stronger inhibitory effect than this of AG had the following common structural feature: an imidazole side-chain in C-3 position, with a substituted or non-substituted aromatic ring in the C-2 position and an aliphatic chain ( n-butyl or n-octyl) or a phenyl moiety on the nitrogen of the pyrrolidone or piperidone ring. When the C-3 side-chain did not bear any imidazole ring, no activity was observed. Respective K i values for the competitive inhibition exerted by the more potent inhibitors 10, 11, 13 and 21 with androstenedione as substrate were 19.2, 20.3, 16.8 and 15.4 μM, respectively ( K i AG = 77.0 μM).

1,3,4,10b-Tetrahydro-4-phenylpyrido[2,1-a]isoindole-2,6-dione

The piperidone ring in the title compound, C 18 H 15 NO 2 , is in a chair conformation. Coordination at the N atom is planar. The phenyl substituent and the bridgehead H atom at the ring junction are cis and in axial orientations with respect to the piperidone ring.

Heteronuclear NMR studies of the chromone alkaloids and revision of the structure of some piperidino-chromone alkaloids.

The 13C-NMR spectra of seven chromone alkaloids isolated from Schumanniophyton magnificum have been obtained. Assignment of signals was carried out with the help of heteronuclear coupling experiments and other correlation techniques on the alkaloids and their acyl derivatives. On the basis of the signals observed the structures of the piperidino-alkaloid schumannificine and its N-methyl and anhydro analogues have been revised to that of a piperidone ring linked to the noreugenin via a carbon-carbon bond and a lactol bridge.

Structural study of ethyl 3-methyl-9-oxo-3-azabicyclo[3.3.1]nonane-1-carboxylate by two-dimensional NMR spectroscopy

Ethyl 3-methyl-9-oxo-3-azabicyclo[3.3.1]nonane-1-carboxylate has been studied by 1H, 13C and 2D NMR spectroscopy in order to establish its conformational behaviour. The combined use of COSY and 1H-13C correlation spectra helped in the unambiguous and complete assignment of the bicyclic carbon and proton resonances. It is found that the piperidone ring displays a slightly fattened chair conformation with the N-methyl group in the equatorial position, while a twist-chair form seems to be favoured for the cyclohexanone one. Two preferred orientations migth be proposed for the ethoxycarbonyl moiety.

X‐Ray structures of endo and exo isomers of 6‐tert‐butyl‐2‐piperidone‐4,5‐(n‐phenyldicarboximide)

AbstractThe configuration of the two isomers obtained by the Diels‐Alder reaction of the 2‐azadiene I with N‐phenylmaleimide II (scheme) is established by X‐ray diffraction; The cycloaddition takes place with a high endo selectivity. The geometry of the two isomers is similar and the piperidone ring has a twist conformation in both molecules.

Synthesis, structural, conformational and pharmacological study of N-2′-acyloxyalkylnorgranatanones

A series of N-2′-acyloxyalkylnorgranatanones have been synthesized and studied by 1H and 13C NMR spectroscopy, and the crystal structure of N[2′(α,α-diphenylpropionyloxy)ethyl]norgranatanone 2 has been determined by X-ray diffraction. In CDCl 3 solution, these compounds can be described through an equilibrium between 2 flattened chair-chair conformers by nitrogen inversion. Piperidone ring is more flattened than the piperidine one, and a slight preference for the form with the N-substituent axial to the piperidone ring might be proposed. The title compounds are able to antagonize the histamine and acetylcholine-induced contractions of guinea pig ileum with IC 50's ranging from 2 × 10 −4 to 1.81 × 10 −6 M.

Synthesis and structural, conformational and pharmacological study of N-β(or γ)acyloxyalkylnortropinones

A series of N-β(or γ)acyloxyalkylnortropinones was synthesized and studied by 1H and 13C NMR spectroscopies, and the crystal structure of N-[β-(diphenylacetyloxy)ethyl] nortropinone 1 was determined by X-ray diffraction. In CDCl 3 solution, the compounds studied display the same preferred conformation. The pyrrolidine and piperidone rings adopt a flattened N8 envelope and distorted chair conformation, puckered at N8 and flattened at C3, respectively, with the N-substituent in the axial position with respect to the piperidone ring. The ability of the title compounds to antagonize the histamine and acetylcholine-induced contraction of guinea pig ileum is also reported. An initial structure-activity relationship is proposed.

Conformational study of N-substituted 9-azabicyclo[3.3.1]nonan-3-ones

N-Substituted 9-azabicyclo [3.3.1] nonan-3-ones have been studied by 1H- and 13C-NMR spectroscopy. In CDCl 3 solutions, these ketones can be described through an equilibrium between two flattened chair-chair conformers by nitrogen inversion. The piperidone ring is more flattened than the piperidine one and has a slight preference for the form with the N-substituent axial to the piperidone ring. The contribution of the conformers with piperidone or piperidine rings in an ideal boat conformation must be low. The application of the Altona empirical equation supports this hypothesis.

Epiderstatin, a new inhibitor of the mitogenic activity induced by epidermal growth factor. II. Structure elucidation.

The structure of a novel antibiotic, epiderstatin, was determined as 4-[3-((Z)-3,5-dimethyl-2-oxopiperidin-6-ylidene)-2-oxopropyl]-2, 6-piperidinedione by spectroscopic analyses of 1H NMR, 13C NMR, 1H-1H correlation spectroscopy (COSY), 13C-1H COSY, heteronuclear multiple bond correlation spectroscopy, UV and IR spectra. The antibiotic belongs to the glutarimide antibiotics, however, the characteristic feature of epiderstatin is that it has a piperidone ring instead of a cyclohexanone ring.

Synthesis, structural and conformational study of N‐β(or γ)‐acyloxyalkylnortropinones

AbstractA series of N‐β(γ)‐acyloxyalkylnortropinones have been synthesized and studied by 1H and 13C nmr spectroscopy, and the crystal structure of N‐[γ‐(p‐chlorophenylcarbonyloxy)propyl]nortropinone 4 has been determined by X‐ray diffraction. The compounds studied display in deuteriochloroform solution the same preferred conformation. The pyrrolidine and piperidone rings adopt a flattened N‐8 envelope and distorted chair conformation, puckered at N‐8 and flattened at C‐3 respectively, with the N‐substituent in axial position with respect to the piperidone ring. These results are in close agreement with that found for compound 4 in the crystalline state.

ChemInform Abstract: Conformational Study of N‐Substituted 8‐Azabicyclo(3.2.1)octan‐3‐ones

Abstract N-Substituted 8-azabicyclo[3.2.1]octan-3-ones have been studied by 1H and 13C NMR spectroscopy. In CDCl3 solutions, these ketones display the same preferred conformation. The pyrrolidine and piperidone rings adopt a flattened N-8 envelope and distorted chair conformation, puckered at N-8 and flattened at C-3, respectively, with the N-substituent in axial position with respect to the piperidone ring.

Structural and conformational study of 3,7-disubstituted 3,7-diazabicyclo[3.3.1]nonan-9-ones

3-Alkyl-7-methyl-3,7-diazabicyclo[3.3.1]nonan-9-ones have been studied by 1H- and 13C-NMR spectroscopy. In CDCl 3 solutions, these ketones adopt a flattened chair—chair conformation with the N-substituents in the equatorial position. From the smallest (R = CH 3) to the largest (R = CH(CH 3) 2) substituent, an increase of the distortion for the N-alkylated piperidone ring is observed.

The 13C NMR spectra, isomerism, and conformational analysis of substituted piperidin-4-ones

The 13C NMR spectra of 15 stereoisomers of 1-mono-, 1,2-di-, and 1,2,5-trisubstituted piperidin-4-ones were investigated, and the stereochemical orientations of the substituents and the conformation relationships were established. For the series of piperidones a method for determination of the absolute confirmation of the C(2) center of the piperidone ring is proposed on the basis of the chemical shifts of the methyl groups in the 1-s-α-phenylethyl substituent at the nitrogen atom in the preferred rotamers with respect to the C(1)-N bond.

Conformational study of N-substituted 8-azabicyclo[3.2.1]octan-3-ones

N-Substituted 8-azabicyclo[3.2.1]octan-3-ones have been studied by 1H and 13C NMR spectroscopy. In CDCl 3 solutions, these ketones display the same preferred conformation. The pyrrolidine and piperidone rings adopt a flattened N-8 envelope and distorted chair conformation, puckered at N-8 and flattened at C-3, respectively, with the N-substituent in axial position with respect to the piperidone ring.

Stereoisomerism in macrocyclic bis(piperidones)

The reaction of a polysubstituted 3,5-dimethylene-4-piperidone with aliphatic diamines leads to macrocyclic products, namely, 3,3′,5,5′-di(methylaminoalkyl-aminomethyl)-bridged bis(piperidones). The latter compounds are formed as mixtures of cis, trans-isomers, and isolated in the form of cis,cis-isomers. 13C-NMR spectral analysis has shown that these compounds also exhibit characteristic syn-anti isomerism associated with the relative orientation of the 3,5-substituents on opposite piperidone rings.

The crystal and molecular structure of N-(3,4,5-trimethoxycinnamoyl)-Δ3-piperidine-2-one, an amide alkaloid (piperlongumine), C17H19NO5

The crystals of C17H19NO5 belong to the monoclinic space group P21/n with a = 15.793(3), b = 4.089(4), c = 24.649(5) Å, β = 97.56(3)° V = 157 8(2) Å3, and Z = 4. The structure was solved by MULTAN 78 and refined by full-matrix least-squares to a final R of 0.053 for 1863 observed reflections. X-ray crystallography has revealed that the molecule is the Δ3 isomer and not the Δ5 isomer suggested originally from nmr spectroscopy. The piperidyl nitrogen is sp2 hybridized with its electron lone pair involved in conjugation with the carbonyl groups. The piperidone ring adopts a distorted boat conformation. An interesting feature of the structure is the formation of two C(ethylenic)—H … O(keto) intramolecular hydrogen bonds which stabilize the molecular conformation.

Steric control of the asymmetric synthesis of N-substitued 2-methyl-4-piperidones

Transmission of the iodomethylate of 1,2-dimethyl-4-piperidone by (S)-sec-butylamine gives 1-(S-sec-butyl)-2S-methyl-4-piperidone in 33% optical yield while transamination by (S)-l-methyl-2-phenylethylamine gives a 1:1 diastereomeric mixture of 1-(l-methyl-2-phenylethyl)-2 -methyl-4-piperidone.The decrease in the optical yield is related to the facile opening of the piperidone ring at the C-N bond with subsequent recyclization. The13C MIR data indicate that all the diastereomers of the 4-piperidones obtained are in the chair conformation with predominantly equatorial orientation of the methyl group at C(2). The chiral optical properties were studied and the absolution configurations of the 4-piperidones obtained were established.