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Bernhard Wunsch - One of the best experts on this subject based on the ideXlab platform.
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Chemoenzymatic synthesis of enantiomerically pure tricyclic Benzomorphan analogues
Tetrahedron: Asymmetry, 2006Co-Authors: Christian Ketterer, Stefan Grimme, Edgar Weckert, Bernhard WunschAbstract:Abstract The key step in the synthesis of enantiomerically pure Benzomorphan analogous tricyclic amines 2 is the kinetic resolution of secondary alcohol 7 using the lipase from Pseudomonas fluorescence . The ( S )-configured alcohol ( S )- 7 and the ( R )-configured ester ( R )- 8 were obtained in good yield (40% and 46%, respectively) and excellent enantiomeric excess (99% ee and 98.4% ee, respectively). A diastereoselective oxa-Pictet-Spengler reaction of ( S )- 7 with ethyl glyoxalate (O HC–CO 2 Et) followed by a Dieckmann cyclization provided the tricyclic ring system 11 , which allowed the diastereoselective introduction of an amino group at the 6-position. The absolute configuration of alcohol ( S )- 7 was determined with the tricyclic alcohol 13 . The quantum mechanically calculated specific optical rotation of ( S , S , S )-configured alcohol 13 is in accordance with the measured specific rotation of the synthesized compound. Moreover, X-ray crystal structure analysis of the synthesized compound, determined with the three-beam interference method, proved the ( S , S , S )-configuration of 13 . The enantiomerically pure dimethylamine 12 showed moderate affinity toward σ 2 receptors.
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Benzomorphan analogous cns agents synthesis of homochiral epoxybenzocyclooctenamines
Tetrahedron, 1994Co-Authors: Bernhard Wunsch, Matthias Zott, Georg HofnerAbstract:Abstract The crucial steps in the preparation of the enantiomerically pure amine 5 from the enol ester 3 are: 1. Stereoselective reduction of the enol ester 3 to give the β-hydroxy ester 6 ; 2. elimination of the hydroxy group of 6 according to the method of Barton and McCombie; 3. Hofmann rearrangement of the amide 12 with [bis(trifluoroacetoxy)iodo]benzene to yield the ammonium chloride 14 ·HCl. In contrast to the racemic amines (±)- 1a and (±)- 2a the homochiral amine 5 did not influence the behaviour of mice. Therefore, we conclude that 5 after intraperitoneal application has no effects on the central nervous system.
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Tricyclic Benzomorphan analogues by intramolecular Oxa-Pictet-Spengler reaction
Tetrahedron: Asymmetry, 1993Co-Authors: Bernhard Wunsch, Matthias ZottAbstract:The key step in the regio- and stereoselective preparation of the Benzomorphan analogues 9, 10a, 10b, 14 and 15 is an intramolecular Oxa-Pictet-Spengler reaction. Masked as an acetal the carbonyl component is connected via an amide to the 2-phenylethanol component (7,12). © 1993.
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stereoselektive synthese neuer zentral wirksamer tricyclen vom Benzomorphan typ mit 2 phenylethylamin partialstruktur
Archiv Der Pharmazie, 1993Co-Authors: Bernhard Wunsch, Georg Hofner, Gerd BauschkeAbstract:Die Addition des mit LDA deprotonierten Glycinesters 6 an das Homophthalaldehydmonoacetal 5 liefert den β-Hydroxyester 7, der sich nach Reduktion zu den racemischen 2,6-Epoxy-3-benzoxocin-5-aminen (+/−)-12 und (+/−)-13 cyclisieren las. Die Schlusselverbindungen fur die Gewinnung von 12 und 13 in enantiomerenreiner Form sind die Hydroxyacetale (R,S,R)-22 und (R,S,S)-23: (R,S,R)-22 last sich stereoselektiv durch Addition der Aryllithiumverbindung 21b bzw. der Aryltitanverbindung 21c an das neue Serinal-Aquivalent (R,S)-20 gewinnen; die Reduktion des Ketons (R,S)-24 mit LiAlH4 bei −78°C fuhrt uberwiegend (>95%) zu dem diastereomeren Hydroxyacetal (R,S,S)-23. Mit Saure werden (R,S,R)-22 und (R,S,S)-23 in die tricyclischen Urethane (S,S,R)-25 und (R,S,S)-30 uberfuhrt, die sich zu den Dimethylaminen (S,S,R)-12 und (R,S,S)-13 reduzieren und methylieren lassen (ee > 97%). Analog werden die enantiomeren Amine (R,R,S)-12 und (S,R,R)-13 ausgehend von (R)-Serin dargestellt. Die relative Konfiguration von (R,S,R)-22 wird mit Hilfe von Molecular Dynamics Rechnungen (Sybyl 5.4) in Kombination mit NOE-Messungen bewiesen.- Nach Applikation beider Enantiomere von 12, 13, 27 und 32 lassen sich bei Mausen typische Symptome fur eine zentrale Dampfung beobachten. Im Essigsaure Writhing-Test sind (S,S,R)-12, (S,R,R)-13, (R,S,S)-13, (S,S,R)-27, (R,R,S)-27 und (R,S,S)-32 stark analgetisch wirksam mit ED50 Werten in der Grosenordnung des ED50-Wertes von Tramadol-HCl. Stereoselective Synthesis of Novel Centrally Active Benzomorphan- Type Tricycles with 2-Phenylethylamine Substructure Addition of the LDA-deprotonated glycine ester 6 to the homophthalaldehyde monoacetal 5 yields the β-hydroxyester 7 which is cyclized after reduction to give the racemic 2,6-epoxy-3-benzoxocin-5-aminens (+/−)-12 and (+/−)-13. The key intermediates for the synthesis of 12 and 13 in enantiomerically pure form are the hydroxyacetals (R,S,R)-22 and (R,S,S)-23: (R,S,R)-22 is stereoselectively prepared by addition of the aryllithiumcompound 21b or the aryltitan-compound 21c to the new serinal equivalent (R,S)-20; reduction of the ketone (R,S)-24 with LiAlH4 at −78°C affords the diastereomeric hydroxyacetal (R,S,S)-23 predominantly (>95%). With acid (R,S,R)-22 and (R,S,S)-23 are transformed into the tricyclic ure-thanes (S,S,R)-25 and (R,S,S)-30, which are reduced and methylated to yield the dimethylamines (S,S,R)-12 and (R,S,S)-13 (ee > 97%), respectively. Analogously the enantiomeric amines (R,R,S)-12 and (S,R,R)-13 are prepared starting form (R)-serine. The relative configuration of (R,S,R)-22 is confirmed by molecular dynamics calculations (Sybyl 5,4) combined with NOE-measurements.- Symptoms typical for sedation are observed after application of both enantiomers of 12, 13, 27, and 32 to mice. In the acetic acid writhing test (mouse) (S,S,R)-12, (S,R,R)-13. (R,S,S)-13, (S,S,R)-27, (R,R,S)-27, and (R,S,S)-32 exhibit strong analgesic effects with ED50-values in the range of the ED50-value of tramadol-HCl.
Carmela Parenti - One of the best experts on this subject based on the ideXlab platform.
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exploiting the power of stereochemistry in drug action 3 2s 6s 11s 8 hydroxy 6 11 dimethyl 1 4 5 6 tetrahydro 2 6 methano 3 benzazocin 3 2h yl n phenylpropanamide as potent sigma 1 receptor antagonist
ACS Chemical Neuroscience, 2020Co-Authors: Rita Turnaturi, Lorella Pasquinucci, Agostino Marrazzo, Orazio Prezzavento, Emanuele Amata, Santina Chiechio, Margherita Grasso, Maria Dichiara, Carmela ParentiAbstract:(+)-(2S,6S,11S)- and (−)-(2R,6R,11R)-Benzomorphan derivatives have a different binding affinity for sigma-1 (σ1R) and opioid receptors, respectively. In this study, we describe the synthesis of the...
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novel n substituted Benzomorphan based compounds from mor agonist dor antagonist to biased unbiased mor agonists
ACS Medicinal Chemistry Letters, 2020Co-Authors: Lorella Pasquinucci, Carmela Parenti, Agostino Marrazzo, Orazio Prezzavento, Emanuele Amata, Zafiroula Georgoussi, Carmen M Ruizcantero, Paschalina Pallaki, Enrique J Cobos, Emanuela ArenaAbstract:Modifications at the basic nitrogen of the Benzomorphan scaffold allowed the development of compounds able to segregate physiological responses downstream of the receptor signaling, opening new possibilities in opioid drug development. Alkylation of the phenyl ring in the N-substituent of the MOR-agonist/DOR-antagonist LP1 resulted in retention of MOR affinity. Moreover, derivatives 7a, 7c, and 7d were biased MOR agonists toward ERK1,2 activity stimulation, whereas derivative 7e was a low potency MOR agonist on adenylate cyclase inhibition. They were further screened in the mouse tail flick test and PGE2-induced hyperalgesia and drug-induced gastrointestinal transit.
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Benzomorphan skeleton, a versatile scaffold for different targets: A comprehensive review
European journal of medicinal chemistry, 2018Co-Authors: Rita Turnaturi, Lorella Pasquinucci, Agostino Marrazzo, Lucia Montenegro, Rosalba Parenti, Carmela ParentiAbstract:Despite the fact that the Benzomorphan skeleton has mainly been employed in medicinal chemistry for the development of opioid analgesics, it is a versatile structure. Its stereochemistry, as well as opportune modifications at the phenolic hydroxyl group and at the basic nitrogen, play a pivotal role addressing the Benzomorphan-based compounds to a specific target. In this review, we describe the structure activity-relationships (SARs) of Benzomorphan-based compounds acting at sigma 1 receptor (σ1R), sigma 2 receptor (σ2R), voltage-dependent sodium channel, N-Methyl-d-Aspartate (NMDA) receptor-channel complex and other targets. Collectively, the SARs data have highlighted that the Benzomorphan nucleus could be regarded as a useful template for the synthesis of drug candidates for different targets.
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Benzomorphan scaffold for opioid analgesics and pharmacological tools development: A comprehensive review.
European journal of medicinal chemistry, 2018Co-Authors: Rita Turnaturi, Carmela Parenti, Agostino Marrazzo, Lorella PasquinucciAbstract:Benzomorphan, derived by morphine skeleton simplification, has been the subject of exploration in medicinal chemistry for the development of new drugs and pharmacological tools to explore opioid pharmacology in vitro and in vivo. Building upon these evidences, the design and synthesis of Benzomorphan-based compounds, appropriately modified at the basic nitrogen and/or the phenolic hydroxyl (8-OH) group, represent a valid and versatile strategy to obtain analgesics. In this review, to improve the body of information in this field, we report structure activity-relationships (SARs) of Benzomorphan-based compounds analysing data literature of last 25 years. Collectively, SARs data highlighted that the Benzomorphan nucleus represents a template in the achievement of a specific functional profile, by modifying N-substituent or 8-OH group.
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evaluation of n substitution in 6 7 Benzomorphan compounds
Bioorganic & Medicinal Chemistry, 2010Co-Authors: Lorella Pasquinucci, Simone Ronsisvalle, Carmela Parenti, Agostino Marrazzo, Orazio Prezzavento, Emanuele Amata, Zafiroula Georgoussi, Danai-dionysia Fourla, Giovanna M. Scoto, Giuseppina AricòAbstract:6,7-Benzomorphan derivatives, exhibiting different mu, delta, and kappa receptor selectivity profiles depending on the N-substituent, represent a useful skeleton for the synthesis of new and better analgesic agents. In this work, an aromatic ring and/or alkyl residues have been used with an N-propanamide or N-acetamide spacer for the synthesis of a new series of 5,9-dimethyl-2'-hydroxy-6,7-Benzomorphan derivatives (12-22). Data obtained by competition binding assays showed that the mu opioid receptor seems to prefer an interaction with the 6,7-Benzomorphan ligands having an N-substituent with a propanamide spacer and less hindered amide. Highly stringent features are required for delta receptor interaction, while an N-acetamide spacer and/or bulkier amide could preferentially lead to kappa receptor selectivity. In the propanamide series, compound 12 (named LP1) displayed high mu affinity (Ki=0.83 nM), good delta affinity (Ki=29 nM) and low affinity for the kappa receptor (Ki=110 nM), with a selectivity ratio delta/mu and kappa/mu of 35.1 and 132.5, respectively. Further, in the adenylyl cyclase assay, LP1 displayed a mu/delta agonist profile, with IC50 values of 4.8 and 12 nM at the mu and delta receptors, respectively. The antinociceptive potency of LP1 in the tail-flick test after sc administration in rat was comparable with the potency of morphine (ED50=2.03 and 2.7 mg/kg, respectively), and was totally reversed by naloxone. LP1, possessing a mu/delta agonist profile, could represent a lead in further developing Benzomorphan-based ligands with potent in vivo analgesic activity and a reduced tendency to induce side effects.
Lorella Pasquinucci - One of the best experts on this subject based on the ideXlab platform.
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exploiting the power of stereochemistry in drug action 3 2s 6s 11s 8 hydroxy 6 11 dimethyl 1 4 5 6 tetrahydro 2 6 methano 3 benzazocin 3 2h yl n phenylpropanamide as potent sigma 1 receptor antagonist
ACS Chemical Neuroscience, 2020Co-Authors: Rita Turnaturi, Lorella Pasquinucci, Agostino Marrazzo, Orazio Prezzavento, Emanuele Amata, Santina Chiechio, Margherita Grasso, Maria Dichiara, Carmela ParentiAbstract:(+)-(2S,6S,11S)- and (−)-(2R,6R,11R)-Benzomorphan derivatives have a different binding affinity for sigma-1 (σ1R) and opioid receptors, respectively. In this study, we describe the synthesis of the...
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novel n substituted Benzomorphan based compounds from mor agonist dor antagonist to biased unbiased mor agonists
ACS Medicinal Chemistry Letters, 2020Co-Authors: Lorella Pasquinucci, Carmela Parenti, Agostino Marrazzo, Orazio Prezzavento, Emanuele Amata, Zafiroula Georgoussi, Carmen M Ruizcantero, Paschalina Pallaki, Enrique J Cobos, Emanuela ArenaAbstract:Modifications at the basic nitrogen of the Benzomorphan scaffold allowed the development of compounds able to segregate physiological responses downstream of the receptor signaling, opening new possibilities in opioid drug development. Alkylation of the phenyl ring in the N-substituent of the MOR-agonist/DOR-antagonist LP1 resulted in retention of MOR affinity. Moreover, derivatives 7a, 7c, and 7d were biased MOR agonists toward ERK1,2 activity stimulation, whereas derivative 7e was a low potency MOR agonist on adenylate cyclase inhibition. They were further screened in the mouse tail flick test and PGE2-induced hyperalgesia and drug-induced gastrointestinal transit.
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Benzomorphan skeleton, a versatile scaffold for different targets: A comprehensive review
European journal of medicinal chemistry, 2018Co-Authors: Rita Turnaturi, Lorella Pasquinucci, Agostino Marrazzo, Lucia Montenegro, Rosalba Parenti, Carmela ParentiAbstract:Despite the fact that the Benzomorphan skeleton has mainly been employed in medicinal chemistry for the development of opioid analgesics, it is a versatile structure. Its stereochemistry, as well as opportune modifications at the phenolic hydroxyl group and at the basic nitrogen, play a pivotal role addressing the Benzomorphan-based compounds to a specific target. In this review, we describe the structure activity-relationships (SARs) of Benzomorphan-based compounds acting at sigma 1 receptor (σ1R), sigma 2 receptor (σ2R), voltage-dependent sodium channel, N-Methyl-d-Aspartate (NMDA) receptor-channel complex and other targets. Collectively, the SARs data have highlighted that the Benzomorphan nucleus could be regarded as a useful template for the synthesis of drug candidates for different targets.
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Benzomorphan scaffold for opioid analgesics and pharmacological tools development: A comprehensive review.
European journal of medicinal chemistry, 2018Co-Authors: Rita Turnaturi, Carmela Parenti, Agostino Marrazzo, Lorella PasquinucciAbstract:Benzomorphan, derived by morphine skeleton simplification, has been the subject of exploration in medicinal chemistry for the development of new drugs and pharmacological tools to explore opioid pharmacology in vitro and in vivo. Building upon these evidences, the design and synthesis of Benzomorphan-based compounds, appropriately modified at the basic nitrogen and/or the phenolic hydroxyl (8-OH) group, represent a valid and versatile strategy to obtain analgesics. In this review, to improve the body of information in this field, we report structure activity-relationships (SARs) of Benzomorphan-based compounds analysing data literature of last 25 years. Collectively, SARs data highlighted that the Benzomorphan nucleus represents a template in the achievement of a specific functional profile, by modifying N-substituent or 8-OH group.
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evaluation of n substitution in 6 7 Benzomorphan compounds
Bioorganic & Medicinal Chemistry, 2010Co-Authors: Lorella Pasquinucci, Simone Ronsisvalle, Carmela Parenti, Agostino Marrazzo, Orazio Prezzavento, Emanuele Amata, Zafiroula Georgoussi, Danai-dionysia Fourla, Giovanna M. Scoto, Giuseppina AricòAbstract:6,7-Benzomorphan derivatives, exhibiting different mu, delta, and kappa receptor selectivity profiles depending on the N-substituent, represent a useful skeleton for the synthesis of new and better analgesic agents. In this work, an aromatic ring and/or alkyl residues have been used with an N-propanamide or N-acetamide spacer for the synthesis of a new series of 5,9-dimethyl-2'-hydroxy-6,7-Benzomorphan derivatives (12-22). Data obtained by competition binding assays showed that the mu opioid receptor seems to prefer an interaction with the 6,7-Benzomorphan ligands having an N-substituent with a propanamide spacer and less hindered amide. Highly stringent features are required for delta receptor interaction, while an N-acetamide spacer and/or bulkier amide could preferentially lead to kappa receptor selectivity. In the propanamide series, compound 12 (named LP1) displayed high mu affinity (Ki=0.83 nM), good delta affinity (Ki=29 nM) and low affinity for the kappa receptor (Ki=110 nM), with a selectivity ratio delta/mu and kappa/mu of 35.1 and 132.5, respectively. Further, in the adenylyl cyclase assay, LP1 displayed a mu/delta agonist profile, with IC50 values of 4.8 and 12 nM at the mu and delta receptors, respectively. The antinociceptive potency of LP1 in the tail-flick test after sc administration in rat was comparable with the potency of morphine (ED50=2.03 and 2.7 mg/kg, respectively), and was totally reversed by naloxone. LP1, possessing a mu/delta agonist profile, could represent a lead in further developing Benzomorphan-based ligands with potent in vivo analgesic activity and a reduced tendency to induce side effects.
Agostino Marrazzo - One of the best experts on this subject based on the ideXlab platform.
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exploiting the power of stereochemistry in drug action 3 2s 6s 11s 8 hydroxy 6 11 dimethyl 1 4 5 6 tetrahydro 2 6 methano 3 benzazocin 3 2h yl n phenylpropanamide as potent sigma 1 receptor antagonist
ACS Chemical Neuroscience, 2020Co-Authors: Rita Turnaturi, Lorella Pasquinucci, Agostino Marrazzo, Orazio Prezzavento, Emanuele Amata, Santina Chiechio, Margherita Grasso, Maria Dichiara, Carmela ParentiAbstract:(+)-(2S,6S,11S)- and (−)-(2R,6R,11R)-Benzomorphan derivatives have a different binding affinity for sigma-1 (σ1R) and opioid receptors, respectively. In this study, we describe the synthesis of the...
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novel n substituted Benzomorphan based compounds from mor agonist dor antagonist to biased unbiased mor agonists
ACS Medicinal Chemistry Letters, 2020Co-Authors: Lorella Pasquinucci, Carmela Parenti, Agostino Marrazzo, Orazio Prezzavento, Emanuele Amata, Zafiroula Georgoussi, Carmen M Ruizcantero, Paschalina Pallaki, Enrique J Cobos, Emanuela ArenaAbstract:Modifications at the basic nitrogen of the Benzomorphan scaffold allowed the development of compounds able to segregate physiological responses downstream of the receptor signaling, opening new possibilities in opioid drug development. Alkylation of the phenyl ring in the N-substituent of the MOR-agonist/DOR-antagonist LP1 resulted in retention of MOR affinity. Moreover, derivatives 7a, 7c, and 7d were biased MOR agonists toward ERK1,2 activity stimulation, whereas derivative 7e was a low potency MOR agonist on adenylate cyclase inhibition. They were further screened in the mouse tail flick test and PGE2-induced hyperalgesia and drug-induced gastrointestinal transit.
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Benzomorphan skeleton, a versatile scaffold for different targets: A comprehensive review
European journal of medicinal chemistry, 2018Co-Authors: Rita Turnaturi, Lorella Pasquinucci, Agostino Marrazzo, Lucia Montenegro, Rosalba Parenti, Carmela ParentiAbstract:Despite the fact that the Benzomorphan skeleton has mainly been employed in medicinal chemistry for the development of opioid analgesics, it is a versatile structure. Its stereochemistry, as well as opportune modifications at the phenolic hydroxyl group and at the basic nitrogen, play a pivotal role addressing the Benzomorphan-based compounds to a specific target. In this review, we describe the structure activity-relationships (SARs) of Benzomorphan-based compounds acting at sigma 1 receptor (σ1R), sigma 2 receptor (σ2R), voltage-dependent sodium channel, N-Methyl-d-Aspartate (NMDA) receptor-channel complex and other targets. Collectively, the SARs data have highlighted that the Benzomorphan nucleus could be regarded as a useful template for the synthesis of drug candidates for different targets.
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Benzomorphan scaffold for opioid analgesics and pharmacological tools development: A comprehensive review.
European journal of medicinal chemistry, 2018Co-Authors: Rita Turnaturi, Carmela Parenti, Agostino Marrazzo, Lorella PasquinucciAbstract:Benzomorphan, derived by morphine skeleton simplification, has been the subject of exploration in medicinal chemistry for the development of new drugs and pharmacological tools to explore opioid pharmacology in vitro and in vivo. Building upon these evidences, the design and synthesis of Benzomorphan-based compounds, appropriately modified at the basic nitrogen and/or the phenolic hydroxyl (8-OH) group, represent a valid and versatile strategy to obtain analgesics. In this review, to improve the body of information in this field, we report structure activity-relationships (SARs) of Benzomorphan-based compounds analysing data literature of last 25 years. Collectively, SARs data highlighted that the Benzomorphan nucleus represents a template in the achievement of a specific functional profile, by modifying N-substituent or 8-OH group.
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evaluation of n substitution in 6 7 Benzomorphan compounds
Bioorganic & Medicinal Chemistry, 2010Co-Authors: Lorella Pasquinucci, Simone Ronsisvalle, Carmela Parenti, Agostino Marrazzo, Orazio Prezzavento, Emanuele Amata, Zafiroula Georgoussi, Danai-dionysia Fourla, Giovanna M. Scoto, Giuseppina AricòAbstract:6,7-Benzomorphan derivatives, exhibiting different mu, delta, and kappa receptor selectivity profiles depending on the N-substituent, represent a useful skeleton for the synthesis of new and better analgesic agents. In this work, an aromatic ring and/or alkyl residues have been used with an N-propanamide or N-acetamide spacer for the synthesis of a new series of 5,9-dimethyl-2'-hydroxy-6,7-Benzomorphan derivatives (12-22). Data obtained by competition binding assays showed that the mu opioid receptor seems to prefer an interaction with the 6,7-Benzomorphan ligands having an N-substituent with a propanamide spacer and less hindered amide. Highly stringent features are required for delta receptor interaction, while an N-acetamide spacer and/or bulkier amide could preferentially lead to kappa receptor selectivity. In the propanamide series, compound 12 (named LP1) displayed high mu affinity (Ki=0.83 nM), good delta affinity (Ki=29 nM) and low affinity for the kappa receptor (Ki=110 nM), with a selectivity ratio delta/mu and kappa/mu of 35.1 and 132.5, respectively. Further, in the adenylyl cyclase assay, LP1 displayed a mu/delta agonist profile, with IC50 values of 4.8 and 12 nM at the mu and delta receptors, respectively. The antinociceptive potency of LP1 in the tail-flick test after sc administration in rat was comparable with the potency of morphine (ED50=2.03 and 2.7 mg/kg, respectively), and was totally reversed by naloxone. LP1, possessing a mu/delta agonist profile, could represent a lead in further developing Benzomorphan-based ligands with potent in vivo analgesic activity and a reduced tendency to induce side effects.
Hui Shi - One of the best experts on this subject based on the ideXlab platform.
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diastereoselective synthesis of 3 4 Benzomorphan derivatives via tandem 5 1 hemiaminalization of 2 aminoaryl divinyl ketones
Organic Letters, 2016Co-Authors: Chengjie Feng, Hui ShiAbstract:A novel tandem formal [5 + 1]/hemiaminalization reaction based on the readily available (2-aminoaryl)divinyl ketones and various nucleophiles has been developed. The reaction represents a highly efficient and convenient methodology for the synthesis of 3,4-Benzomorphan derivatives with high diastereoselectivity, and three new bonds and two rings are successively formed in one step under mild, metal-free conditions.
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Diastereoselective Synthesis of 3,4-Benzomorphan Derivatives via Tandem [5 + 1]/Hemiaminalization of (2-Aminoaryl)divinyl Ketones
2016Co-Authors: Chengjie Feng, Hui ShiAbstract:A novel tandem formal [5 + 1]/hemiaminalization reaction based on the readily available (2-aminoaryl)divinyl ketones and various nucleophiles has been developed. The reaction represents a highly efficient and convenient methodology for the synthesis of 3,4-Benzomorphan derivatives with high diastereoselectivity, and three new bonds and two rings are successively formed in one step under mild, metal-free conditions