- Synthesis of the ABC ring system of manzamine A.
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A synthesis of the core ABC ring system of the manzamine alkaloids is described, starting from arecoline. The key steps involve a Claisen rearrangement to set up a 4-substituted-3-methylenepiperidine and a stereoselective azomethine ylide dipolar cycloaddition reaction. Condensation of the aldehyde 6 and sarcosine ethyl ester hydrochloride salt gives an intermediate azomethine ylide, which undergoes an intramolecular cycloaddition reaction to set up two new rings and three new chiral centers stereoselectively. The aldehyde 6 was not a suitable substrate for related azomethine ylide cycloaddition reactions with other amines. However, the related dimethyl acetal 26 could be condensed with a variety of amines to give the desired tricyclic products. The cycloaddition reaction with N-methyl or N-allyl glycine ethyl ester gave almost exclusively the exo adduct, whereas cycloaddition with glycine ethyl ester gave the endo adduct.
- Coldham, Iain,Crapnell, Katherine M,Fernandez, Joan-Carles,Moseley, Jonathan D,Rabot, Remi
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Read Online
- Enhanced arecoline derivatives as muscarinic acetylcholine receptor M1 ligands for potential application as PET radiotracers
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Supported by their involvement in many neurodegenerative disorders, muscarinic acetylcholine receptors (mAChRs) are an interesting target for PET imaging. Nevertheless, no radiotracer is established in clinical routine. Within this work we aim to develop novel PET tracers based on the structure of arecoline. Fifteen novel arecoline derivatives were synthesized, characterized and tested for their affinity to the mAChRs M1-M5 and the conceivable off-target acetylcholinesterase. Five arecoline derivatives and arecoline were labeled with carbon-11 in good yields. Arecaidine diphenylmethyl ester (3b), arecaidine bis(4-fluorophenyl)methyl ester (3c) and arecaidine (4-bromophenyl)(4-fluorophenyl)methyl ester (3e) showed a tremendous gain in mAChR affinity compared to arecoline and a pronounced subtype selectivity for M1. Metabolic stability and serum protein binding of [11C]3b and [11C]3c were in line with properties of established brain tracers. Nonspecific binding of [11C]3c was prevalent in kinetic and endpoint experiment on living cells as well as in autoradiography on native mouse brain sections, which motivates us to decrease the lipophilicity of this substance class prior to in vivo experiments.
- Ozenil, Marius,Pacher, Katharina,Balber, Theresa,Vraka, Chrysoula,Roller, Alexander,Holzer, Wolfgang,Spreitzer, Helmut,Mitterhauser, Markus,Wadsak, Wolfgang,Hacker, Marcus,Pichler, Verena
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- Collective total synthesis of tetracyclic diquinane lycopodium alkaloids (+)-paniculatine, (-)-magellanine, (+)-magellaninone and analogues thereof
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The collective total synthesis of tetracyclic diquinane Lycopodium alkaloids, (+)-paniculatine, (-)-magellanine, (+)-magellaninone, and two analogues (-)-13-epi-paniculatine and (+)-3-hydroxyl-13-dehydro-paniculatine, has been accomplished. By logic-guide
- Jiang, Shi-Zhi,Lei, Ting,Wei, Kun,Yang, Yu-Rong
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p. 5612 - 5615
(2015/02/19)
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- Iridium-catalyzed enantioselective hydrogenation of unsaturated heterocyclic acids
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Spiral binding: A highly enantioselective hydrogenation of unsaturated heterocyclic acids has been developed by using chiral iridium/spirophosphino oxazoline catalysts (see scheme; BArF-=tetrakis[3,5- bis(trifluoromethyl)phenyl]borate, Boc=tert-butoxycarbonyl). This reaction provided an efficient method for the preparation of optically active heterocyclic acids with excellent enantioselectivities. Copyright
- Song, Song,Zhu, Shou-Fei,Pu, Liu-Yang,Zhou, Qi-Lin
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supporting information
p. 6072 - 6075
(2013/07/05)
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- Synthesis of 3-azabicyclo [4.1.0]heptane-1-carboxylic acid
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A full study on the synthesis of 3-azabicyclo[4.1.0]heptane-1-carboxylic acid is described.Three different approaches were investigated in order to achieve an efficient synthesis of this unnatural aminoacid.The optimized synthetic route relies upon three key steps: (i) diazomalonate insertion on 4-phtalimido 1-butene, (ii) intramolecular cyclization and (iii) chemoselective reduction of the resulting lactam.Due to its bicyclic nature and conformational constraints, this aminoacid may be an useful building block in medicinal chemistry.
- Napolitano, Carmela,Borriello, Manuela,Cardullo, Francesca,Donati, Daniele,Paio, Alfredo,Manfredini, Stefano
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experimental part
p. 5492 - 5497
(2010/08/07)
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- 1H-Indole-Pyridinecarboxamide and 1H-Indole-Piperidinecarboxamide Compounds
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Compounds of formula (I): wherein: A represents a divalent radical: wherein: Z represents an oxygen atom or a sulphur atom,R6 represents a hydrogen atom, an alkyl, alkenyl, arylalkyl or polyhaloalkyl group or a substituted, linear or branched alkyl chain, represents a single bond or a double bond,R1, R2, R3 and R4 represent a hydrogen or halogen atom,an alkyl, alkoxy, hydroxy, cyano, nitro, polyhaloalkyl or optionally substituted amino group, or a linear or branched alkyl chain substituted by one or more groups,R5 represents a hydrogen atom or an alkyl, aminoalkyl or hydroxyalkyl group,X and Y represent a hydrogen atom or an alkyl group,Ra, Rb, Rc and Rd represent a hydrogen or halogen atom, an alkyl, hydroxy, alkoxy, cyano, nitro, polyhaloalkyl, optionally substituted amino group, or a substituted, linear or branched alkyl chain,Re represents a hydrogen atom or an alkyl, arylalkyl or alkenyl group or a substituted, linear or branched alkyl chain, their enantiomers, diastereoisomers, and N-oxides, and also addition salts thereof with a pharmaceutically acceptable acid or base.
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Page/Page column 8
(2009/10/21)
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- Asymmetric synthesis of hydroisoquinoline derivatives, a key intermediate for manzamine synthesis, by diels-alder reaction using 4-amino-2-siloxybutadiene
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A novel method for the synthesisof chiral hydroisoquinolines by asymmetricDiels-Alder reaction of nitrogen-containing dienophiles and suitably protected aminosiloxybutadienes has been developed.
- Mihara, Yasuhiro,Matsumura, Tomoaki,Terauchi, Yuki,Akiba, Masakatsu,Arai, Shigeru,Nishida, Atsushi
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experimental part
p. 1520 - 1527
(2010/04/01)
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- Proteasome inhibitors: Synthesis and activity of arecoline oxide tripeptide derivatives
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We describe the synthesis and biological activities of a series of methyl 3,4-epoxypiperidine-3-carboxylate tripeptide derivatives that inhibit the chymotryptic and tryptic active sites of the 20S proteasome. Of the series, compound 2 which contains 3-hydroxy-2-methylbenzoyl group at its N-terminal position, displayed the greatest inhibitory potency (IC50 1 μM). All derivatives showed favourable pharmacokinetic properties.
- Marastoni, Mauro,McDonald, John,Baldisserotto, Anna,Canella, Alessandro,Risi, Carmela De,Pollini, Gian Piero,Tomatis, Roberto
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p. 1965 - 1968
(2007/10/03)
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- Iminosugars: Potential inhibitors of liver glycogen phosphorylase
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The first synthesis of the single isomers 3R, 4R, 5R); 3S,4S,5S); 3R,4R,5S) and 3S,4S, 5R) of 5-hydroxymethyl-piperidine-3,4-diol from Arecolin is reported, including the synthesis of a series of N-substituted derivatives of the 3R,4R,5R)-isomer Isofagomi
- Jakobsen, Palle,Lundbeck, Jane M,Kristiansen, Marit,Breinholt, Jens,Demuth, Helle,Pawlas, Jan,Torres Candela, Maria P,Andersen, Birgitte,Westergaard, Niels,Lundgren, Karsten,Asano, Naoki
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p. 733 - 744
(2007/10/03)
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- SYNTHESIS OF SUBSTITUTED TETRAHYDROPYRIDINES AND M-HYDROXYBENZOIC ACIDS
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A series of substituted 1,2,3,6- (5) and 1,2,5,6-tetrahydropyridines (6) have been synthesised via intramolecular 1,6-Michael addition of methoxycarbonyl-2,4-dienylamines (10).The kinetics of these reactions have been investigated and an explanation of substituent effects is advanced.Also a new route to m-hydroxybenzoic acids has been established by cyclisation of substituted hexa-3,4:5,6-dienoic acids.
- Clinch, K.,Marquez, C. J.,Parrott, M. J.,Ramage, R.
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p. 239 - 258
(2007/10/02)
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