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Jean-pierre Hurvois - One of the best experts on this subject based on the ideXlab platform.
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electrochemical access to 8 1 phenyl ethyl 1 4 dioxa 8 aza spiro 4 5 decane 7 carbonitrile application to the asymmetric syntheses of myrtine and alkaloid 241d
Journal of Organic Chemistry, 2014Co-Authors: Van Ha Vu, Fadila Louafi, Ronan Marion, Nicolas Girard, Vincent Dorcet, Thierry Roisnel, Jean-pierre HurvoisAbstract:The total syntheses of both enantiomers of trans-quinolizidine (+)-myrtine and cis-2,4,6-trisubstituted piperidine alkaloid (+)-241D are reported here. Our approach was based on the N-Boc-directed metalation of enantiopure 4-piperidone (−)-11, which was prepared in four steps from α-amino nitrile 6 through a stereoselective alkylation–reduction decyanation process. α-Amino nitrile 6 was prepared at the anode through electrochemical oxidation of 4-piperidone (+)-5. In our study, α-phenylethylamine (α-PEA) allowed an efficient 1–3 stereoinduction, and an orthogonal cleavage of the N-Boc protecting group in piperidone derivatives was carried out by stirring them in a suspension of SnCl4·(Et2O)2 complex in diethyl ether. When appropriate, the er’s were determined by proton and carbon NMR spectroscopy utilizing (+)-tert-butylphenylphosphinothioic acid and (+)-DBTA as chiral solvating agents.
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electrochemical access to 8 1 phenyl ethyl 1 4 dioxa 8 aza spiro 4 5 decane 7 carbonitrile application to the asymmetric syntheses of myrtine and alkaloid 241d
Journal of Organic Chemistry, 2014Co-Authors: Van Ha Vu, Fadila Louafi, Ronan Marion, Nicolas Girard, Vincent Dorcet, Thierry Roisnel, Jean-pierre HurvoisAbstract:The total syntheses of both enantiomers of trans-quinolizidine (+)-myrtine and cis-2,4,6-trisubstituted piperidine alkaloid (+)-241D are reported here. Our approach was based on the N-Boc-directed metalation of enantiopure 4-piperidone (−)-11, which was prepared in four steps from α-amino nitrile 6 through a stereoselective alkylation–reduction decyanation process. α-Amino nitrile 6 was prepared at the anode through electrochemical oxidation of 4-piperidone (+)-5. In our study, α-phenylethylamine (α-PEA) allowed an efficient 1–3 stereoinduction, and an orthogonal cleavage of the N-Boc protecting group in piperidone derivatives was carried out by stirring them in a suspension of SnCl4·(Et2O)2 complex in diethyl ether. When appropriate, the er’s were determined by proton and carbon NMR spectroscopy utilizing (+)-tert-butylphenylphosphinothioic acid and (+)-DBTA as chiral solvating agents.
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Electrochemical Access to 8‑(1-Phenyl-ethyl)-1,4-dioxa-8-aza-spiro[4.5]decane-7-carbonitrile. Application to the Asymmetric Syntheses of (+)-Myrtine and Alkaloid (+)-241D
2014Co-Authors: Fadila Louafi, Ronan Marion, Nicolas Girard, Vincent Dorcet, Thierry Roisnel, Jean-pierre HurvoisAbstract:The total syntheses of both enantiomers of trans-quinolizidine (+)-myrtine and cis-2,4,6-trisubstituted piperidine alkaloid (+)-241D are reported here. Our approach was based on the N-Boc-directed metalation of enantiopure 4-piperidone (−)-11, which was prepared in four steps from α-amino nitrile 6 through a stereoselective alkylation–reduction decyanation process. α-Amino nitrile 6 was prepared at the anode through electrochemical oxidation of 4-piperidone (+)-5. In our study, α-phenylethylamine (α-PEA) allowed an efficient 1–3 stereoinduction, and an orthogonal cleavage of the N-Boc protecting group in piperidone derivatives was carried out by stirring them in a suspension of SnCl4·(Et2O)2 complex in diethyl ether. When appropriate, the er’s were determined by proton and carbon NMR spectroscopy utilizing (+)-tert-butylphenylphosphinothioic acid and (+)-DBTA as chiral solvating agents
Erik De Clercq - One of the best experts on this subject based on the ideXlab platform.
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design synthesis and cytotoxic properties of novel 1 4 2 alkylaminoethoxy phenylcarbonyl 3 5 bis arylidene 4 Piperidones and related compounds
European Journal of Medicinal Chemistry, 2007Co-Authors: Umashankar Das, Erik De Clercq, Jane Alcorn, Anuraag Shrivastav, Rajendra K Sharma, Jan Balzarini, J R DimmockAbstract:The 3,5-bis(arylidene)-4-Piperidones 1 contain the 1,5-diaryl-3-oxo-1,4-pentadienyl pharmacophore which is considered to interact at a complementary binding site in susceptible neoplasms. The hypothesis was formulated that the presence of an acyl group attached to the piperidyl nitrogen atom in series 1 may interact with an additional binding site thereby enhancing cytotoxic potencies. This concept led to the synthesis of various N-acyl-3,5-bis(arylidene)-4-Piperidones 3-7 many of which displayed significant cytotoxicity towards a variety of cancer cell lines. A comparison of the potencies between the compounds in series 1 and the related nonquaternary analogues 3-6 revealed that in approximately half of the comparisons made, the N-acyl analogues had increased potencies.
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3 5 bis phenylmethylene 1 n arylmaleamoyl 4 Piperidones a novel group of cytotoxic agents
Journal of Enzyme Inhibition and Medicinal Chemistry, 2003Co-Authors: Jonathan R Dimmock, Amitabh Jha, Gordon A Zello, Theresa M Allen, Anuraag Shrivastav, Rajendra K Sharma, Jan Balzarini, Ponniah Selvakumar, Cheryl Santos, Erik De ClercqAbstract:A series of novel 3,5-bis(phenylmethylene)-1-(N-arylmaleamoyl)-4-Piperidones 3 have been synthesized which displayed potent cytotoxicity towards human Molt 4/C8 and CEM T-lymphocytes as well as murine P388 and L1210 leukemic cells. In contrast, the related N-arylmaleamic acids 4 possessed little or no cytotoxicity in these four screens. Molecular modeling revealed certain interplanar and bond angles and interatomic distances which were perceived to contribute to the observed bioactivity as well as providing suggestions for future structural modifications of the Piperidones 3. Evaluation of representative compounds in series 3 and 4 on the activity of human N-myristoyltransferase revealed that, at the maximum concentration utilized, namely 250 μM, only weak inhibiting properties were displayed by some of the compounds in series 4. Various members of series 3 and 4 were well tolerated in mice.
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cytotoxic n 4 3 aryl 3 oxo 1 propenyl phenylcarbonyl 3 5 bis phenylmethylene 4 Piperidones and related compounds
European Journal of Medicinal Chemistry, 2002Co-Authors: Jonathan R Dimmock, Amitabh Jha, Gordon A Zello, Wilson J Quail, Eliud O Oloo, Kurt H Nienaber, Earl S Kowalczyk, Theresa M Allen, Cheryl L Santos, Erik De ClercqAbstract:Abstract A series of 4-carboxychalcones 1 were prepared and coupled to 3,5-bis(phenylmethylene)-4-piperidone (2) giving rise to a novel series of N-[4-(3-aryl-3-oxo-1-propenyl)phenylcarbonyl]-3,5-bis(phenylmethylene)-4-Piperidones (3). Molecular simplification of the amides 3 led to the formation of the corresponding N-(3-aryl-1-oxo-2-propenyl)-3,5-bis(phenylmethylene)-4-Piperidones (4). A cytotoxic evaluation of the compounds in series 1–4 utilized murine P388 and L1210 cells as well as human Molt 4/C8 and CEM T-lymphocytes. In general, the compounds displayed significant toxicity; the IC50 values of 54% of the enones were less than 10 μM when all four screens were considered and less than 1 μM for all members of series 3 in the P388 assay. Various correlations were established between the potencies of the compounds in series 1, 3 and 4 and the Hammett σ, Hansch π and molecular refractivity constants of the aryl substituents. Several torsion angles and interatomic distances of five representative compounds in series 3 and 4 were determined by X-ray crystallography, some of which contributed to the observed bioactivity. The marked cytotoxicity and lack of murine toxicity of most of the compounds described in this study, as well as their selective toxicity towards different tumour cell lines, revealed that development of the enones 2–4 as novel candidate antineoplastic agents should be pursued.
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cytotoxic evaluation of some 3 5 diarylidene 4 Piperidones and various related quaternary ammonium compounds and analogs
Journal of Pharmaceutical Sciences, 1994Co-Authors: Jonathan R Dimmock, Theresa M Allen, V K Arora, J W Quail, U Pugazhenthi, G Y Kao, Erik De ClercqAbstract:A number of 3,5-diarylidene-4-Piperidones (1) and some related quaternary ammonium salts (5) as well as closely related analogs were prepared principally as candidate cytotoxic agents in two screens. The first test system used an average of 54 human tumor cell lines from eight neoplastic diseases, namely leukemia, melanoma, colon, non-small-cell lung, small-cell lung, central nervous system, ovarian, and renal cancers. Selective toxicity was demonstrated by some of the compounds, especially toward leukemia. The second screen used L 1210 lymphoid leukemia cells. In general, the compounds were less cytotoxic than the reference drug melphalan in both screens. Linear plots were made between the Hammett (σ), fragment (f), and molar refractivity (MR) constants of the nuclear substituents in series 1 and 5with the IC50 figures of both the human tumor cell lines and L 1210 cells. Evaluation against the human tumor cell lines revealed that increases in the f values were correlated with elevation of cytotoxicity in both series 1 and 5; MR constants were also important in series 5. In the L 1210 screen, σ and MR constants were positively correlated with cytotoxicity. X-ray crystallography was undertaken on 3,5-bis-[[4′-(methylthio)phenyl]methylene]-1-methyl-4-piperidone methiodide (5d), which had significant cytotoxicity, and 3,5-bis(4-pyridylmethylene)-1-methyl-4-piperidone methiodide (6), which was virtually inactive in both screens. A number of structural features were noted, and in particular a smaller interplanar angle made by one of the arylidene groups with the central piperidine ring in the case of 5d than either of the 4-pyridylmethylene moieties in 6 may contribute to the variation in cytotoxicity between these two compounds. Eleven compounds which were examined for activity against a panel of 12 viruses were shown to display only marginal potencies or to be inactive at the highest concentrations utilized. Two compounds with slight activity both had the hydrophilic carboxylate ion in the aryl rings. From this study, various conclusions pertaining to future molecular modification with a view to increasing cytotoxic potency were made.
Jonathan R Dimmock - One of the best experts on this subject based on the ideXlab platform.
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induction of apoptosis via proteasome inhibition in leukemia lymphoma cells by two potent Piperidones
Cellular Oncology, 2018Co-Authors: Lisett Contreras, Armando Varelaramirez, Umashankar Das, Jonathan R Dimmock, Ruben I Calderon, Hongyu Zhang, Yuan Quan, Rachid Skouta, Renato J AguileraAbstract:Previously, compounds containing a piperidone structure have been shown to be highly cytotoxic to cancer cells. Recently, we found that the piperidone compound P2 exhibits a potent anti-neoplastic activity against human breast cancer-derived cells. Here, we aimed to evaluate two piperidone compounds, P1 and P2, for their potential anti-neoplastic activity against human leukemia/lymphoma-derived cells. Cytotoxicity and apoptosis induction were evaluated using MTS, annexin V-FITC/PI and mitochondrial membrane potential polychromatic assays to confirm the mode of action of the piperidone compounds. The effects of compound P1 and P2 treatment on gene expression were assessed using AmpliSeq analysis and, subsequently, confirmed by RT-qPCR and Western blotting. We found that the two related piperidone compounds P1 and P2 selectively killed the leukemia/lymphoma cells tested at nanomolar concentrations through induction of the intrinsic apoptotic pathway, as demonstrated by mitochondrial depolarization and caspase-3 activation. AmpliSeq-based transcriptome analyses of the effects of compounds P1 and P2 on HL-60 acute leukemia cells revealed a differential expression of hundreds of genes, 358 of which were found to be affected by both. Additional pathway analyses revealed that a significant number of the common genes were related to the unfolded protein response, implying a possible role of the two compounds in the induction of proteotoxic stress. Subsequent analyses of the transcriptome data revealed that P1 and P2 induced similar gene expression alterations as other well-known proteasome inhibitors. Finally, we found that Noxa, an important mediator of the activity of proteasome inhibitors, was significantly upregulated at both the mRNA and protein levels, indicating a possible role in the cytotoxic mechanism induced by P1 and P2. Our data indicate that the cytotoxic activity of P1 and P2 on leukemia/lymphoma cells is mediated by proteasome inhibition, leading to activation of pro-apoptotic pathways.
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a novel class of Piperidones exhibit potent selective and pro apoptotic anti leukemia properties
Oncology Letters, 2016Co-Authors: Larissa Mesquita Nunes, Mohammad Hossain, Armando Varelaramirez, Umashankar Das, Yoshira M Ayalamarin, Jonathan R Dimmock, Renato J AguileraAbstract:In the present pre-clinical study, a series of 1-[3-(2-methoxyethylthio)-propionyl]-3,5- bis(benzylidene)-4 Piperidones and structurally-related compounds were observed to be cytotoxic in vitro to three human leukemia cell lines, namely Nalm-6, CEM and Jurkat. The 50% cytotoxic concentration (CC50) values of the three cell lines ranged between 0.9-126.4 µM and 0.3-11.7 µM at 24 and 48 h subsequent to exposure, respectively. The two lead compounds with sub-micromolar CC50 concentrations, 1-(2-methoxyethylthio-propionyl)-3,5-bis(benzylidene)-4 piperidone (2a) and 3,5-bis(4-fluorobenzylidene)-1-[3-(2-methoxyethyl sulfinyl)-propionyl]-4-piperidone (3e), were selected for additional analyses. Several strategies were undertaken to determine whether the above Piperidones caused cell death via apoptosis or necrosis on T-lymphocyte leukemia Jurkat cells. The results revealed that the two Piperidones caused phosphatidylserine externalization, mitochondrial depolarization and activation of caspase-3, which are all biochemical hallmarks of apoptosis. In addition, the selected Piperidones displayed selective cytotoxicity towards leukemia cells, and were less toxic in non-cancerous control cells. Therefore, the findings of the present study revealed that the novel Piperidones 2a and 3e exert a selective cytotoxic effect on lymphocyte leukemia cells by favoring the activation of the intrinsic/mitochondrial apoptotic pathway.
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1 3 2 hydroxyethylsulfanyl propanoyl 3 5 bis benzylidene 4 Piperidones a novel cluster of p glycoprotein dependent multidrug resistance modulators
Bioorganic & Medicinal Chemistry Letters, 2016Co-Authors: Umashankar Das, Hari N Pati, Zoltan Barath, Akos Csonka, Joseph Molnar, Jonathan R DimmockAbstract:A series of 1-[3-(2-hydroxyethylsulfanyl)propanoyl]-3,5-bis(benzylidene)-4-Piperidones 4a-e display promising P-glycoprotein dependent multidrug resistance (MDR) revertant properties and are significantly more potent than a reference drug verapamil when evaluated against L-5178Y MDR lymphoma cells. These dienones may be referred to as dual agents having both MDR revertant properties and tumour-selective cytotoxicity. In particular, 3,5-bis(4-chlorobenzylidene)-1-[3-(2-hydroxyethylsulfanyl]propanoyl-4-piperidone 4d emerged as a lead molecule for further development based on its MDR revertant properties, cytotoxic potencies and tumour-selective toxicity. The structure-activity relationships reveal important structural requirements for further designing of potent MDR revertants.
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3 5 bis phenylmethylene 1 n arylmaleamoyl 4 Piperidones a novel group of cytotoxic agents
Journal of Enzyme Inhibition and Medicinal Chemistry, 2003Co-Authors: Jonathan R Dimmock, Amitabh Jha, Gordon A Zello, Theresa M Allen, Anuraag Shrivastav, Rajendra K Sharma, Jan Balzarini, Ponniah Selvakumar, Cheryl Santos, Erik De ClercqAbstract:A series of novel 3,5-bis(phenylmethylene)-1-(N-arylmaleamoyl)-4-Piperidones 3 have been synthesized which displayed potent cytotoxicity towards human Molt 4/C8 and CEM T-lymphocytes as well as murine P388 and L1210 leukemic cells. In contrast, the related N-arylmaleamic acids 4 possessed little or no cytotoxicity in these four screens. Molecular modeling revealed certain interplanar and bond angles and interatomic distances which were perceived to contribute to the observed bioactivity as well as providing suggestions for future structural modifications of the Piperidones 3. Evaluation of representative compounds in series 3 and 4 on the activity of human N-myristoyltransferase revealed that, at the maximum concentration utilized, namely 250 μM, only weak inhibiting properties were displayed by some of the compounds in series 4. Various members of series 3 and 4 were well tolerated in mice.
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cytotoxic n 4 3 aryl 3 oxo 1 propenyl phenylcarbonyl 3 5 bis phenylmethylene 4 Piperidones and related compounds
European Journal of Medicinal Chemistry, 2002Co-Authors: Jonathan R Dimmock, Amitabh Jha, Gordon A Zello, Wilson J Quail, Eliud O Oloo, Kurt H Nienaber, Earl S Kowalczyk, Theresa M Allen, Cheryl L Santos, Erik De ClercqAbstract:Abstract A series of 4-carboxychalcones 1 were prepared and coupled to 3,5-bis(phenylmethylene)-4-piperidone (2) giving rise to a novel series of N-[4-(3-aryl-3-oxo-1-propenyl)phenylcarbonyl]-3,5-bis(phenylmethylene)-4-Piperidones (3). Molecular simplification of the amides 3 led to the formation of the corresponding N-(3-aryl-1-oxo-2-propenyl)-3,5-bis(phenylmethylene)-4-Piperidones (4). A cytotoxic evaluation of the compounds in series 1–4 utilized murine P388 and L1210 cells as well as human Molt 4/C8 and CEM T-lymphocytes. In general, the compounds displayed significant toxicity; the IC50 values of 54% of the enones were less than 10 μM when all four screens were considered and less than 1 μM for all members of series 3 in the P388 assay. Various correlations were established between the potencies of the compounds in series 1, 3 and 4 and the Hammett σ, Hansch π and molecular refractivity constants of the aryl substituents. Several torsion angles and interatomic distances of five representative compounds in series 3 and 4 were determined by X-ray crystallography, some of which contributed to the observed bioactivity. The marked cytotoxicity and lack of murine toxicity of most of the compounds described in this study, as well as their selective toxicity towards different tumour cell lines, revealed that development of the enones 2–4 as novel candidate antineoplastic agents should be pursued.
Van Ha Vu - One of the best experts on this subject based on the ideXlab platform.
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electrochemical access to 8 1 phenyl ethyl 1 4 dioxa 8 aza spiro 4 5 decane 7 carbonitrile application to the asymmetric syntheses of myrtine and alkaloid 241d
Journal of Organic Chemistry, 2014Co-Authors: Van Ha Vu, Fadila Louafi, Ronan Marion, Nicolas Girard, Vincent Dorcet, Thierry Roisnel, Jean-pierre HurvoisAbstract:The total syntheses of both enantiomers of trans-quinolizidine (+)-myrtine and cis-2,4,6-trisubstituted piperidine alkaloid (+)-241D are reported here. Our approach was based on the N-Boc-directed metalation of enantiopure 4-piperidone (−)-11, which was prepared in four steps from α-amino nitrile 6 through a stereoselective alkylation–reduction decyanation process. α-Amino nitrile 6 was prepared at the anode through electrochemical oxidation of 4-piperidone (+)-5. In our study, α-phenylethylamine (α-PEA) allowed an efficient 1–3 stereoinduction, and an orthogonal cleavage of the N-Boc protecting group in piperidone derivatives was carried out by stirring them in a suspension of SnCl4·(Et2O)2 complex in diethyl ether. When appropriate, the er’s were determined by proton and carbon NMR spectroscopy utilizing (+)-tert-butylphenylphosphinothioic acid and (+)-DBTA as chiral solvating agents.
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electrochemical access to 8 1 phenyl ethyl 1 4 dioxa 8 aza spiro 4 5 decane 7 carbonitrile application to the asymmetric syntheses of myrtine and alkaloid 241d
Journal of Organic Chemistry, 2014Co-Authors: Van Ha Vu, Fadila Louafi, Ronan Marion, Nicolas Girard, Vincent Dorcet, Thierry Roisnel, Jean-pierre HurvoisAbstract:The total syntheses of both enantiomers of trans-quinolizidine (+)-myrtine and cis-2,4,6-trisubstituted piperidine alkaloid (+)-241D are reported here. Our approach was based on the N-Boc-directed metalation of enantiopure 4-piperidone (−)-11, which was prepared in four steps from α-amino nitrile 6 through a stereoselective alkylation–reduction decyanation process. α-Amino nitrile 6 was prepared at the anode through electrochemical oxidation of 4-piperidone (+)-5. In our study, α-phenylethylamine (α-PEA) allowed an efficient 1–3 stereoinduction, and an orthogonal cleavage of the N-Boc protecting group in piperidone derivatives was carried out by stirring them in a suspension of SnCl4·(Et2O)2 complex in diethyl ether. When appropriate, the er’s were determined by proton and carbon NMR spectroscopy utilizing (+)-tert-butylphenylphosphinothioic acid and (+)-DBTA as chiral solvating agents.
Fadila Louafi - One of the best experts on this subject based on the ideXlab platform.
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electrochemical access to 8 1 phenyl ethyl 1 4 dioxa 8 aza spiro 4 5 decane 7 carbonitrile application to the asymmetric syntheses of myrtine and alkaloid 241d
Journal of Organic Chemistry, 2014Co-Authors: Van Ha Vu, Fadila Louafi, Ronan Marion, Nicolas Girard, Vincent Dorcet, Thierry Roisnel, Jean-pierre HurvoisAbstract:The total syntheses of both enantiomers of trans-quinolizidine (+)-myrtine and cis-2,4,6-trisubstituted piperidine alkaloid (+)-241D are reported here. Our approach was based on the N-Boc-directed metalation of enantiopure 4-piperidone (−)-11, which was prepared in four steps from α-amino nitrile 6 through a stereoselective alkylation–reduction decyanation process. α-Amino nitrile 6 was prepared at the anode through electrochemical oxidation of 4-piperidone (+)-5. In our study, α-phenylethylamine (α-PEA) allowed an efficient 1–3 stereoinduction, and an orthogonal cleavage of the N-Boc protecting group in piperidone derivatives was carried out by stirring them in a suspension of SnCl4·(Et2O)2 complex in diethyl ether. When appropriate, the er’s were determined by proton and carbon NMR spectroscopy utilizing (+)-tert-butylphenylphosphinothioic acid and (+)-DBTA as chiral solvating agents.
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electrochemical access to 8 1 phenyl ethyl 1 4 dioxa 8 aza spiro 4 5 decane 7 carbonitrile application to the asymmetric syntheses of myrtine and alkaloid 241d
Journal of Organic Chemistry, 2014Co-Authors: Van Ha Vu, Fadila Louafi, Ronan Marion, Nicolas Girard, Vincent Dorcet, Thierry Roisnel, Jean-pierre HurvoisAbstract:The total syntheses of both enantiomers of trans-quinolizidine (+)-myrtine and cis-2,4,6-trisubstituted piperidine alkaloid (+)-241D are reported here. Our approach was based on the N-Boc-directed metalation of enantiopure 4-piperidone (−)-11, which was prepared in four steps from α-amino nitrile 6 through a stereoselective alkylation–reduction decyanation process. α-Amino nitrile 6 was prepared at the anode through electrochemical oxidation of 4-piperidone (+)-5. In our study, α-phenylethylamine (α-PEA) allowed an efficient 1–3 stereoinduction, and an orthogonal cleavage of the N-Boc protecting group in piperidone derivatives was carried out by stirring them in a suspension of SnCl4·(Et2O)2 complex in diethyl ether. When appropriate, the er’s were determined by proton and carbon NMR spectroscopy utilizing (+)-tert-butylphenylphosphinothioic acid and (+)-DBTA as chiral solvating agents.
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Electrochemical Access to 8‑(1-Phenyl-ethyl)-1,4-dioxa-8-aza-spiro[4.5]decane-7-carbonitrile. Application to the Asymmetric Syntheses of (+)-Myrtine and Alkaloid (+)-241D
2014Co-Authors: Fadila Louafi, Ronan Marion, Nicolas Girard, Vincent Dorcet, Thierry Roisnel, Jean-pierre HurvoisAbstract:The total syntheses of both enantiomers of trans-quinolizidine (+)-myrtine and cis-2,4,6-trisubstituted piperidine alkaloid (+)-241D are reported here. Our approach was based on the N-Boc-directed metalation of enantiopure 4-piperidone (−)-11, which was prepared in four steps from α-amino nitrile 6 through a stereoselective alkylation–reduction decyanation process. α-Amino nitrile 6 was prepared at the anode through electrochemical oxidation of 4-piperidone (+)-5. In our study, α-phenylethylamine (α-PEA) allowed an efficient 1–3 stereoinduction, and an orthogonal cleavage of the N-Boc protecting group in piperidone derivatives was carried out by stirring them in a suspension of SnCl4·(Et2O)2 complex in diethyl ether. When appropriate, the er’s were determined by proton and carbon NMR spectroscopy utilizing (+)-tert-butylphenylphosphinothioic acid and (+)-DBTA as chiral solvating agents