Showing papers by "Ulrike Holzgrabe published in 1989"
TL;DR: The 3,7-diazabicyclo[3.3.1]nonanone 7 and 12 showed opioid-like effects, whereas the diazaadamantanone 13 is a peripheral analgesic.
Abstract: Die 1,3-Diazaadamantan-6-one 13–18 werden aus den 4-Piperidonen 1–3 synthetisiert, wobei verschiedene Reaktionsbedingungen zu konfigurationsisomeren Verbindungen fuhren. Das Auftreten entspr. Isomerer wird auch bei den 3,7- Diazabicyclo[3.3.1]nonan-9-onen 8 und 9 beobachtet. Die Konfigurationsbestimmung erfolgt mittels 1H-NMR- und 13C-NMR-Spektroskopie. Wahrend sich die Diazabicyclo[3.3.1]nonanone 7 und 12 im pharmakologischen Test als opioide Agonisten erwiesen, ist das Diazaadamantanon 13 peripher analgetisch wirksam.
Synthesis, Stereochemistry and Analgesic Activity of 3,7-Diazabicyclo[3.3.1]nonan-9-ones and 1,3-Diazaadamantan-6-ones
The 1,3-diazaadamantan-6-ones 13–18 are synthesized from the 4-piperidones 1–3. Different conditions lead to stereoisomeric structures. The 3,7-diazabicyclo[3.3.1]nonan-9-ones 8 and 9 show similar geometrical isomerisms. The configuration is determined by means of 1H-NMR and 13C-NMR spectroscopic data. Whereas the diazabicyclo[3.3.1]nonanones 7 and 12 show opioid-like effects, the diazaadamantanone 13 is a peripheral analgesic.
24 citations
TL;DR: In this paper, the 3,7-diazabicyclo and 1,3-diazaadamantan-6-ones were reduced by sodium borohydride and lithium aluminum hydride in various solvents.
Abstract: Die 3,7-Diazabicyclo[3.3.1]nonan-9-one 1a-c und 1,3-Diazaadamantan-6-one 1d-g werden mit Natriumborhydrid und Lithiumaluminiumhydrid in verschiedenen Losungsmitteln zu den korrespondierenden epimeren Alkoholen umgesetzt, deren Konfigurationen 1H-NMR- und 13C-NMR-spektroskopisch bestimmt werden. Die Ursachen fur den unterschiedlichen sterischen Verlauf der Reduktionen werden diskutiert. Die Umsetzung des 1,3-Diazaadamantan-6-ons. 1f mit Methylmagnesiumiodid in Dichlormethan fuhrt zu dem ringgespaltenen N-alkylierten Produkt 1h.
Reductions of 3,7-Diazabicylo[3.3.1]nonan-9-ones and Corresponding 1,3-Diazaadamantan-6-ones
The 3,7-diazabicyclo[3.3.1]nonan-9-ones 1a-c and 1,3-diazaadamantan-6-ones 1d-g are reduced by sodium borohydride and lithium aluminum hydride in various solvents. The configuration of the so obtained alcohols is determined by means of 1H-NMR and 13C-NMR data. The reasons for the proportion of the epimeric alkohols are discussed. The reaction of the 1,3-diazaadamantan-6-one 1f with methylmagnesium iodide yields the ring-opened N-alkylated product 1h.
10 citations
TL;DR: In this article, a Mannich procedure was used to synthesize the alkyl N-benzyl-4-piperidone-3-carboxylate (1) and the corresponding diester 2 is formed by condensation of pyridine aldehyde, benzylamine and dimethyl 3-oxoglutarate.
Abstract: The alkyl N-benzyl-4-piperidone-3-carboxylate (1) is synthesized by a Mannich procedure from pyridine aldehyde, benzylamine and the monoester of acetonedicarboxylate; the corresponding diester 2 is formed by condensation of pyridine aldehyde, benzylamine and dimethyl 3-oxoglutarate. Isomerism is observed with respect to keto-enol tautomerism and cis or trans substitution of the pyridines. The structure of the enol lb (C₂₄H₂₃N₃O₃) is determined by X-ray analysis: it crystallizes in the triclinic space group P 1 with a = 9.965(2), b = 10.476(2), c = 10.838(2) A, α = 69.48(1), β/3 = 81.56(1), γ = 79.09(1)°, Ζ = 2 and Dₓ = 1.29 g cm⁻³. It is refined to R(unweighted) = 0.047 and R(weighted) = 0.045 using 1459 non-equivalent reflections. The structures of la/b and 2a/b were determined by ¹H and ¹³C NMR data. MNDO calculations of 1a/b are discussed. The enols 1/2b are reduced by sodium borohydride. The configuration of the obtained alcohols is determined by NMR data.
4 citations
TL;DR: In this article, the reaction mechanism of N-benzyl-4-piperidones is characterized by a radical mechanism: the cyclisation product, the methanobenzazocine 2, is formed via a C-3 intermediate, the dehydrogenation products 3 and 4 are obtained from peroxyradicals.
Abstract: Die Cer(IV)sulfat-Oxidationen von N-Benzyl-4-piperidonen sind durch einen radikalischen Reaktionsverlauf gekennzeichnet: die Cyclisierungsprodukte, die Methanobenzazocine 2, werden uber ein Radikal an C-3 gebildet, fur die Dehydrierungsreaktion zu 3 und 4 sind intermediar gebildete Peroxyradikale verantwortlich.
Cerium(IV) Oxidations of β-Aminoketones., VI: Investigations on the Reaction Mechanism
Cerium(IV)sulfate oxidations of N-benzyl-4-piperidones are characterized by a radical mechanism: the cyclisation product, the methanobenzazocine 2, is formed via a C-3 intermediate, the dehydrogenation products 3 and 4 are obtained from peroxyradicals.
4 citations
TL;DR: In this paper, the stereoselectivity of reduction of 5-oxo-2,6-methano-2-benzazocines with NaBH4 and LiAlH4 in various solvents is mainly dependent on the position of the substituents in the piperidone part of the molecule.
Abstract: Die 5-Oxo-2,6-methano-2-benzazocine 2a und 2b werden mit NaBH4 und LiAlH4 in verschiedenen Losungsmitteln reduziert, wobei die Stereoselektivitat der Reduktion stark von der Stellung der Substituenten im Piperidonteil des Molekuls abhangig ist. Die Aufklarung der relativen Konfiguration der epimeren Alkohole erfolgt mit 1H-NMR- und 13C-NMR- spektroskopischen Methoden.
Reductions of 3,11-Dipyridine Substituted 5-Oxo-2,6-methano-6-benz[c]azocine carboxylates
The stereoselectivity of the reduction of 5-Oxo-2,6-methano-2-benzazocines with NaBH4 and LiALH4, respectively, in various solvents is mainly dependent on the position of the substituents in the piperidone part of the molecule. The relative configuration of the epimeric secondary alcohols is determined by means of 1H-NMR and 13C-NMR spectroscopic data.
2 citations