Stereoselective synthesis of (R)-(−)-mianserin

Pawłowska, Jolanta; Czarnocki, Zbigniew; Wojtasiewicz, Krystyna; Maurin, Jan K.

doi:10.1016/s0957-4166(03)00582-2

Cited by 23 publications

(17 citation statements)

References 14 publications

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“…Previous work has reported that the levorotatory enantiomer of Mianserin has the (R)-configuration. 21 As shown in Figure 7, the CD spectrum of reference (À)-(R)-Mianserin in ethanol displayed a broad negative Cotton effect centered at around 258 nm. This band is attributable to the 1 L b transition of the aromatic group.…”

Section: Determination Of the Absolute Configurationmentioning

confidence: 91%

Direct HPLC enantioseparation of chiral aptazepine derivatives on coated and immobilized polysaccharide‐based chiral stationary phases

et al. 2006

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The direct HPLC enantioseparation of Mianserin and a series of aptazepine derivatives is accomplished on polysaccharide-based chiral stationary phases (CSPs). The resolutions are performed on the coated-type Chiralcel OD and Chiralpak AD CSPs and on the first commercially available immobilized-type Chiralpak IA CSP, in normal-phase and polar-organic modes. The complete separation of enantiomers of all racemates investigated was successfully achieved under at least one of CSP/eluent combinations employed. Pure alcohols such ethanol or 2-propanol, with a fixed percentage of DEA added, serve as valuable alternatives to the more common n-hexane-based normal-phase eluents in resolution of Mianserin on the AD CSP. In order to study the chiroptical properties of aptazepine derivatives, chromatographic resolutions are carried out at semipreparative scale using Chiralpak AD and Chiralpak IA as CSPs. Nonconventional dichloromethane-based eluents have permitted to expand the chiral resolving ability of the immobilized Chiralpak IA CSP and to perform mg-scale enantioseparations with an analytical-size column. Assignment of the absolute configuration of the separated enantiomers is empirically established by comparing their chiroptical data with those of structurally related Mianserin.

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Section: Determination Of the Absolute Configurationmentioning

confidence: 91%

Direct HPLC enantioseparation of chiral aptazepine derivatives on coated and immobilized polysaccharide‐based chiral stationary phases

et al. 2006

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“…In the field of the stereoselective synthesis of pharmacologically relevant compounds, we presented recently the application of α-phenylethylamine (α-PEA) in the preparation of enantiomerically pure lortalamine analogs [17] and (R)-(−)-mianserin [18] -both compounds being well-known antidepressants. The Bischler-Napieralski cyclization followed by a diastereoselective reduction of the imine bond were the key steps in enantiodivergent synthesis of both enantiomers of N-acetylcalycotomine that were carried out in our laboratory [19].…”

Section: (R)-1-phenylethylamine and Its Analogs As Chiral Auxiliariesmentioning

confidence: 99%

Variety of natural products derived from tryptophan and stereoselective synthesis of tetrahydro-β-carboline derivatives of pharmacological importance

Roszkowski

Czarnocki

Maurin

et al. 2007

International Congress Series

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“…In this context, we have developed a simple and practical two-step synthetic route to some novel series of 6,11-dihydrodibenzo [b,e]azepines from readily available 2-allyl-N-benzylsubstituted anilines (Palma et al, 2004(Palma et al, , 2010. Continuing with our studies on the synthesis of new small and potentially bioactive molecules containing the dihydrodibenzo [b,e]aze-]azepine nucleus, we have now achieved the synthesis of the previously unknown 6,11-dihydro-5H-benzo[b,e]azepine-6-carboxamide, a potentially useful precursor in the synthesis of analogues of some drugs in current use, such as the antidepressant mianserin [systematic name: 2-methyl-1,2,3,4,10,14b- (Pawlowska et al, 2003) and the anti-allergenic and antihistaminic epinastine 3-amino-9,13b-dihydro-1H-dibenz [c,f]imidazo [1,5-a]azepine (Schneider, 1992;Jung et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Diastereoisomeric forms of 11-ethyl-6,11-dihydro-5H-dibenzo[b,e]azepine-6-carboxamide: syntheses and the molecular and supramolecular structure of the minor form (6RS,11RS)-11-ethyl-6,11-dihydro-5H-dibenzo[b,e]azepine-6-carboxamide

et al. 2016

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Compounds containing the tricyclic dibenzo[b,e]azepine system have potential activity in the treatment of a number of diseases. Continuing with our studies on the synthesis of new small and potentially bioactive molecules, a synthetic route, involving acid-catalysed intramolecular Friedel-Crafts cyclization, to the readily separable diastereoisomers of 11-ethyl-6,11-dihydro-5H-dibenzo[b,e]azepine-6-carboxamide, a potentially useful precursor in the synthesis of analogues of some anti-allergenic, antidepressant and antihistaminic drugs currently in use, has been developed starting from 2-allylphenylamine and methyl 2-bromo-2-phenylacetate and proceeding via racemic methyl 2-[(2-allylphenyl)amino]-2-phenylacetate (A) and racemic 2-[(2-allylphenyl)amino]-2-phenylacetamide (B), to give the two diastereoisomers (I) and (II), C17H18N2O. Isomers (I) and (II), and their precursors (A) and (B), have all been fully characterized spectroscopically. Structure analysis of the minor isomer (I) shows that it has the (6RS,11RS) configuration, and that the azepine ring adopts a conformation intermediate between the boat and twist-boat forms, with the carboxamide and ethyl substituents both occupying quasi-equatorial sites. The molecules of (I) are linked by a combination of N-H...O, N-H...π(arene) and C-H...π(arene) hydrogen bonds to form complex sheets. Comparisons are made with the structures of some related compounds.

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Stereoselective synthesis of (R)-(−)-mianserin

Cited by 23 publications

References 14 publications

Direct HPLC enantioseparation of chiral aptazepine derivatives on coated and immobilized polysaccharide‐based chiral stationary phases

Direct HPLC enantioseparation of chiral aptazepine derivatives on coated and immobilized polysaccharide‐based chiral stationary phases

Variety of natural products derived from tryptophan and stereoselective synthesis of tetrahydro-β-carboline derivatives of pharmacological importance

Diastereoisomeric forms of 11-ethyl-6,11-dihydro-5H-dibenzo[b,e]azepine-6-carboxamide: syntheses and the molecular and supramolecular structure of the minor form (6RS,11RS)-11-ethyl-6,11-dihydro-5H-dibenzo[b,e]azepine-6-carboxamide

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