- Application of Proline-Derived (Thio)squaramide Organocatalysts in Asymmetric Diels-Alder and Conjugate Addition Reactions
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The synthesis of chiral proline-derived squaramide and thiosquaramide organocatalysts, which are capable of the dual activation in asymmetric reactions is reported. The (thio)squaramide moiety can form hydrogen bonds to activate the substrates and to stereocontrol the reaction, while the pyrrolidine unit can form enamines to activate carbonyl compounds via aminocatalysis. Comparing the performance of thiosquaramide to squaramide, the Diels Alder reaction of (anthracen-9-yl)acetaldehyde and trans-?-nitrostyrene was examined, which has been investigated in the literature using quantum chemical calculations. Both squaramide and thiosquaramide gave excellent yields (up to 99%) and enantiomeric excess values (up to 98%). Moreover, their catalytic performance was compared in conjugate addition of lawsone to ?,?-unsaturated ?-keto ester.
- Bagi, Péter,Dargó, Gyula,Drahos, László,Huszthy, Péter,Kis, Dávid,Kupai, József,Mátrav?lgyi, Béla,Nagy, Sándor,Tóth, Blanka
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- Synthesis of Chiral Triazole-Based Halogen Bond Donors
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The number of applications that use halogen bonding in the fields of self-assembly, supramolecular aggregation, and catalysis is growing. However, the accessibility of chiral halotriazoles shows that there is still a lot more to explore. The simple click-chemistry is applied for the straightforward synthesis of enantiomerically pure mono- and bidentate as well as multifunctional iodotriazole-based XB donors. The methodology is characterized by a wide variability due to easy access of chiral azides.
- Kaasik, Mikk,Kaabel, Sandra,Kriis, Kadri,J?rving, Ivar,Kanger, T?nis
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supporting information
p. 2128 - 2135
(2019/05/10)
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- Staudinger/aza-Wittig reaction to access Nβ-protected amino alkyl isothiocyanates
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A unified approach to access Nβ-protected amino alkyl isothiocyanates using Nβ-protected amino alkyl azides through a general strategy of Staudinger/aza-Wittig reaction is described. The type of protocol used to access isothiocyanates depends on the availability of precursors and also, especially in the amino acid chemistry, on the behavior of other labile groups towards the reagents used in the protocols; fortunately, we were not concerned about both these factors as precursor-azides were prepared easily by standard protocols, and the present protocol can pave the way for accessing title compounds without affecting Boc, Cbz and Fmoc protecting groups, and benzyl and tertiary butyl groups in the side chains. The present strategy eliminates the need for the use of amines to obtain title compounds and thus, this method is step-economical; additional advantages include retention of chirality, convenient handling and easy purification. A few hitherto unreported compounds were also prepared, and all final compounds were completely characterized by IR, mass, optical rotation, and 1H and 13C NMR studies.
- Santhosh,Durgamma,Shekharappa,Sureshbabu, Vommina V.
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p. 4874 - 4880
(2018/07/15)
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- COMPOUNDS FOR REACTIVATION OF ACETYLCHOLINESTERASE AND RELATED COMPOSITIONS METHODS AND SYSTEMS
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Described herein are oxime compounds capable of inactivating a nerve agent, blood brain barrier (BBB)-penetration, and/or reactivation of nerve agent-inhibited acetylcholinesterase (AChE) and related methods, systems and compositions for inactivation of one or more nerve agents, therapeutic and/or prophylactic treatment of an individual, and/or decomposition of nerve agent for decontamination.
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- Pyrrolidine modified PANF catalyst for asymmetric Michael addition of ketones to nitrostyrenes in aqueous phase
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Three chiral pyrrolidine functionalized polyacrylonitrile fiber catalysts have been designed, prepared, and evaluated for their catalytic performance in asymmetric Michael addition of ketones to nitrostyrenes in water. With the optimized catalysts and conditions in hand, their reaction scope for nitrostyrenes was explored. Then the fiber catalysts were further applied to a packed-bed reactor for continuous-flow Michael addition. Based on the fact that organic solvent can inhibit the catalytic activity, a novel microenvironment catalytic mechanism is proposed.
- Du, Jianguo,Shuai, Bin,Tao, Minli,Wang, Guangwei,Zhang, Wenqin
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p. 2625 - 2631
(2016/05/24)
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- Synthesis and in vivo evaluation of 11C-labeled (1,7-dicarba-closo-dodecaboran-1-yl)-N-{[(2S)-1-ethylpyrrolidin-2-yl]methyl} amide
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Boron clusters, and especially dicarba-closo-dodecaboranes, can be used as hydrophobic pharmacophores in the design of new drugs and radiotracers because of their hydrophobic character, spherical structure, and excellent chemical and photochemical stability. In the present paper, the synthesis and in vivo evaluation of 11C-labeled (1,7-dicarba-closo-dodecaboran-1-yl)-N- {[(2S)-1-ethylpyrrolidin-2-yl]methyl}amide, an analog of the D2 receptor ligand [11C]raclopride, is described. The radiosynthesis was approached by reaction of the demethylated precursor with [11C] CH3I in basic media; moderate radiochemical yields (18.2 ± 2.8%, decay corrected), and excellent radiochemical purities (>98%) were obtained in overall synthesis time of ~50 min. In vivo assays showed a biodistribution pattern with significant uptake in liver, kidneys and lungs at short times (t = 4 min) after administration and increasing accumulation in bladder at longer times (t ≥ 14.5 min). Although brain positron emission tomography scans showed good blood brain barrier penetration, the high unspecific uptake observed in different brain regions impedes its applicability as D2 receptor ligand.
- G?mez-Vallejo, Vanessa,Vázquez, Naiara,Gona, Kiran Babu,Puigivila, Maria,González, Mikel,Sebastián, Eneko San,Martin, Abraham,Llop, Jordi
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p. 209 - 214
(2014/05/06)
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- Stereoselective synthesis of chiral pyrrolidine derivatives of (+)-α-pinene containing a β-amino acid moiety
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We report the synthesis of several enantiopure pyrrolidine derivatives containing a β-amino acid moiety. These novel chiral compounds were prepared through stereospecific chlorosulfonyl isocyanate (CSI) addition to the readily available, natural terpene (+)-α-pinene. Coupling of N-Boc-protected β-amino acid derivatives with various bulky amines and amino acids using the mixed anhydride activation method, followed by N-deprotection, afforded the corresponding chiral amino amides in good yields. Despite the severe steric hindrance anticipated in α-pinene-based heterocycles, efficient coupling of the amino amides and an amino ester with the acyl chloride of N-Cbz-protected (S)-proline provided the corresponding pyrrolidinic pinene derivatives in good yields. Moreover, a convenient synthesis of N-Cbz- and N-Boc-monoprotected (S)-prolinamine is reported. Georg Thieme Verlag Stuttgart New York.
- Vega-Penaloza, Alberto,Sanchez-Antonio, Omar,Escudero-Casao, Margarita,Tasnadi, Gabor,Fueloep, Ferenc,Juaristi, Eusebio
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p. 2458 - 2468
(2013/09/23)
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- Synthesis of new enantiopure thioureas derived from (S)-proline
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Enantiopure thiourea derivatives, containing pyrrolidine ring, were prepared by the reaction of N-Boc-(S)-2-aminomethylpyrrolidine (6) with thioisocyanates 8.
- Wroblewska, Aneta,Mloston, Grzegorz
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p. 509 - 511
(2013/07/25)
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- Design, synthesis and catalytic property of L-proline derivatives as organocatalysts for direct aldol reaction
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A series of chiral prolinamide compounds with pyridine-2, 6-dicarboxylic acid moieties derived from L-proline have been designed and synthesized, their catalytic properties for direct asymmetric aldol reactions were also studied in this article. These catalysts gave the aldol product in high yield (87%) and high enantioselectivity, up to 85%, of the anti-structure at room temperature but gave disappointing results at a lower temperature or when additive was added. Conditions, including solvents, temperature and additives were screened for the reactions. Moreover, the influence of presence of water on yield and stereoselectivity was also discussed. Copyright
- Wang, Lei,Tang, Ruiren,Yang, Hua
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p. 591 - 598
(2013/11/06)
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- 1-alkyl-5-((di)alkylamino) tetrazoles: Building blocks for peptide surrogates
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An approach to the synthesis of 1-alkyl-5-((di)alkylamino)tetrazoles by nucleophilic substitution in 1-alkyl-5-sulfonyltetrazoles with anions generated from the primary or secondary amines was developed. Tolerance of the method to the presence of some fun
- Tymtsunik, Andriy V.,Bilenko, Vitaliy A.,Kokhan, Serhiy O.,Grygorenko, Oleksandr O.,Volochnyuk, Dmitriy M.,Komarov, Igor V.
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experimental part
p. 1174 - 1180
(2012/03/12)
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- Proline-derived aminotriazole ligands: Preparation and use in the ruthenium-catalyzed asymmetric transfer hydrogenation
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The preparation of 2-triazolyl- and 2-triazolylmethylpyrrolidines from L-proline and L-trans-4-hydroxyproline is described, along with their evaluation as chiral ligands in ruthenium-catalyzed asymmetric transfer hydrogenation. Modular evolution of the ligands by introduction of remote substituents is also presented, showing a surprisingly important effect on the performance of the ligands.
- Cambeiro, Xacobe C.,Pericas, Miquel A.
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p. 113 - 124
(2011/04/12)
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- Synthesis of D2 receptor ligand analogs incorporating one dicarba-closo-dodecaborane unit
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Boron clusters, and especially dicarba-closo-dodecaboranes, can be used as hydrophobic pharmacophores in the design of new drugs and radiotracers. In the current Letter, analogs of enantiomeric substituted benzamides (Raclopride and FLB-457) in which the phenyl ring has been substituted by a carborane cage (either orto- or meta-carborane) have been developed as potential D2 receptor antagonists. The formation of intramolecular hydrogen bonds (in solution) and the stability of the new chemical entities have been evaluated by means of 1H NMR and HPLC-MS, respectively.
- Vázquez, Naiara,Gómez-Vallejo, Vanessa,Calvo, Javier,Padro, Daniel,Llop, Jordi
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p. 615 - 618
(2011/03/18)
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- Synthesis of chiral NADH analog based on proline template including thiourea and nicotinic acid moieties
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Chiral reductase-mimicking organic molecule built on proline template incorporating a covalently bound NADH mimic via thiourea, and related reducing agent Hantzsch dihydropyridine, was designed. A synthetic path was developed involving interlinking of chiral proline derivatives with thiourea and subsequent coupling reaction with nicotinoyl chloride. The structure of target compound was studied by x-ray, indicating a double H bond with thiourea hydrogens and oxygen O1 of benzylcarbamate fragment. The reduction of benzil and imines was performed. Taylor & Francis Group, LLC.
- Bagdziunas, Gintautas,Haukka, Matti,Butkus, Eugenijus
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p. 2517 - 2523
(2011/08/07)
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- Condensation approach to aliphatic oligourea foldamers: Helices with N-(Pyrrolidin-2-ylmethyl)ureido junctions
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Caught in a fold: A simple and efficient coupling strategy to make aliphatic oligourea foldamers is reported. Crystal structures show that the pyrrolidine units (red; see picture) do not impair the 2.5-helical folding of the oligoureas. This modular strategy enables assembly of long helical segments containing non-adjacent pyrrolidine units as exemplified by the synthesis of a helix that is approximately 40 long.
- Fremaux, Juliette,Fischer, Lucile,Arbogast, Thomas,Kauffmann, Brice,Guichard, Gilles
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p. 11382 - 11385
(2012/01/06)
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- Functionalized proline with double hydrogen bonding potential: Highly enantioselective Michael addition of carbonyl compounds to β-nitrostyrenes in brine
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Simple synthetic manipulation of S-proline allows access to prolinamides 5-7 as organocatalysts capable of double hydrogen bonding for enantioselective Michael addition reactions of carbonyl compounds to β-nitrostyrenes. It is shown that prolinamide catalyst 7 leads to addition products with a high diastereo- as well as enantioselectivity. The transition state structure involving the binding of electrophilic nitrostyrene via two H-bonds is believed to be further stabilized by π,π stacking interactions mediated by the tosyl ring.
- Saha, Satyajit,Seth, Saona,Moorthy, Jarugu Narasimha
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supporting information; experimental part
p. 5281 - 5286
(2010/11/03)
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- Asymmetric organocatalysis of the addition of acetone to 2-nitrostyrene using N-diphenylphosphinyl-1,2-diphenylethane-1,2-diamine (PODPEN)
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The highly enantioselective addition of acetone to 2-nitrostyrene, using N-diphenylphosphinyl-trans-1,2-diphenylethane-1,2-diamine (PODPEN) as a catalyst, is described.
- Morris, David J.,Partridge, A. Simon,Manville, Charles V.,Racys, Daugidas T.,Woodward, Gary,Docherty, Gordon,Wills, Martin
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supporting information; experimental part
p. 209 - 212
(2010/03/24)
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- Recyclable merrifield resin-supported organocatalysts containing pyrrolidine unit through A3-coupling reaction linkage for asymmetric michael addition
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Merrifield resin-supported pyrrolidine-based chiral organocatalysts A2D through A3-coupling reaction linkage have been developed and found to be highly effective catalysts for the Michael addition reaction of ketones with nitrostyrenes. The rea
- Liu, Jie,Li, Pinhua,Zhang, Yicheng,Ren, Kai,Wang, Lei,Wang, Guanwu
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experimental part
p. 432 - 441
(2012/04/23)
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- The synthesis and biological evaluation of a novel series of C7 non-basic substituted fluoroquinolones as antibacterial agents
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A series of non-basic building blocks was synthesized and introduced to the C7 position of the quinolone nucleus 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid to afford the corresponding fluoroquinolones in 46-85% yield. The antibacterial activity of these new fluoroquinolones was evaluated using a standard broth microdilution technique. The sulfur-containing quinolone, 7-(2-thia-5-azabicyclo[2.2.1]heptan-5-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid exhibited a superior antibacterial activity against quinolone-susceptible and multidrug-resistant strains in comparison with the clinically used fluoroquinolones ciprofloxacin and vancomycin, especially to the Streptococcus pneumonia and multidrug-resistant S. pneumonia clinical isolates. Crown Copyright
- Huang, Xiaoguang,Chen, Dongliang,Wu, Ning,Zhang, Aiqin,Jia, Zhenhua,Li, Xingshu
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scheme or table
p. 4130 - 4133
(2010/04/26)
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- Syntheis of new chiral 5,6,7,8-tetrahydrotetrazolo[1,5-a]pyrazines from α-amino acid derivatives following "click" chemistry
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An efficient and practical synthesis of new chiral fused tetrazoles have been synthesized following [3+2] cycloaddition reaction starting from α-amino acid derivatives.
- Mohapatra, Debendra K.,Maity, Pradip K.,Ghorpade, Ravindra V.,Gurjar, Mukund K.
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scheme or table
p. 865 - 872
(2010/09/16)
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- Highly enantioselective Michael additions in water catalyzed by a PS-supported pyrrolidine
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The development of a highly efficient, polymer-supported organocatalyst for the Michael addition of ketones to nitroolefins is described. A 1,2,3-triazole ring, constructed through a click 1,3-cycloaddition, plays the double role of grafting the chiral pyrrolidine monomer onto the polystyrene backbone and of providing a structural element, complementary to pyrrolidine, key to high catalytic activity and enantioselectivity. Optimal operation in water and full recyclability make the triazole linker attractive for the immobilization of organocatalysts.
- Alza, Esther,Cambeiro, Xacobe C.,Jimenez, Ciril,Pericas, Miquel A.
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p. 3717 - 3720
(2008/02/12)
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- Selenium promoted synthesis of enantiopure pyrrolidines starting from chiral aminoalcohols
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Starting from commercially available enantiomerically pure aminoalcohols and using simple conversions promoted by organoselenium reagents, several enantiomerically pure substituted pyrrolidines were prepared. After double protections (R)- or (S)-2-phenylg
- Tiecco, Marcello,Testaferri, Lorenzo,Bagnoli, Luana,Scarponi, Catalina,Temperini, Andrea,Marini, Francesca,Santi, Claudio
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p. 2758 - 2767
(2008/03/28)
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- Synthesis of new chiral 4,5,6,7-tetrahydro[1,2,3]triazolo[1,5-a]pyrazines from α-amino acid derivatives under mild conditions
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A practical and efficient regioselective synthesis of several new chiral 4,5,6,7-tetrahydro[1,2,3]triazolo[1,5-a]pyrazines is described from α-amino acid derivatives following intramolecular 'click' reaction as the key step. The method obviates product pu
- Mohapatra, Debendra K.,Maity, Pradip K.,Gonnade, Rajesh G.,Chorghade, Mukund S.,Gurjar, Mukund K.
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p. 1893 - 1896
(2008/03/13)
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- Triazolopeptides: chirospecific synthesis and cis/trans prolyl ratios of structural isomers
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As cis/trans prolyl isomerization plays a crucial role in various biological processes, peptide mimics capable of modifying the cis/trans Xaa-Pro ratio are of particular interest. A practical approach toward proline derived triazolopeptides employing [3+2] azide-alkyne cycloadditions as the key reaction step and the analysis of their cis/trans prolyl ratios are reported. Structural investigations indicated the adjustability of both the cis-percentage and the conformational stability toward intramolecular H-bonding effects.
- Paul, Andreas,Bittermann, Holger,Gmeiner, Peter
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p. 8919 - 8927
(2007/10/03)
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- 4-Substituted prolyl sulfonamides as enantioselective organocatalysts for aldol reactions
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A series of prolyl and 4-substituted prolyl sulfonamides were prepared and were evaluated as organocatalysts of asymmetric aldol reaction. Using prolyl methanesulfonamide, 4-benzyloxy-prolyl methanesulfonamide and toluenesulfonamide and 4-hydroxy-prolyl t
- Bellis, Evagelos,Vasilatou, Konstantina,Kokotos, George
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p. 2407 - 2413
(2007/10/03)
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- INHIBITORS OF HUMAN TUMOR-EXPRESSED CCXCKR2
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Pharmaceutical compositions containing organic compounds or salts thereof that serve as modulators for the SDF-1 or I-TAC chemokines are disclosed. The compounds and compositions are useful in the treatment of cancer, especially in the inhibition of cancer proliferation, growth, and metastasis. Methods of interfering with SDF-1 and/or I-TAC binding to the CCXCKR2 receptor and treating cancer using the compounds and pharmaceutical compositions of the present invention are also disclosed.
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- N-arenesulfonyl-2-aminomethylpyrrolidmes - Novel modular ligands and organocatalysts for asymmetric catalysis
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A novel series of (S)-N-arenesulfonyl-2-aminomethylpyrrolidines were prepared in high overall yield starting from N-Boc-L-proline. The mono-sulfonyldiamines were evaluated as organocatalysts in the asymmetric α-amination of propanal using diethyl azadicarboxylate (DEAD) as the amine source. The initially formed α-aminated aldehyde was reduced in situ to the corresponding N-aminooxazolidinone, which was obtained in moderate to high yield in up to 87% ee.
- Dahlin, Nils,Bogevig, Anders,Adolfsson, Hans
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p. 1101 - 1105
(2007/10/03)
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- Novel succinate compounds, compositions and methods of use and preparation
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Novel hydroxamic acid compounds are disclosed. These hydroxamates inhibit peptidyl deformylase (PDF), an enzyme present in prokaryotes. The hydroxymates are useful as antimicrobials and antibiotics. The compounds of the invention display selective inhibition of peptidyl deformylase versus other metalloproteinases such as matrix metalloproteinases (MMPs). Methods of synthesis and of use of the compounds are also disclosed.
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- Thrombin active site inhibitors: Chemical synthesis, in vitro and in vivo pharmacological profile of a novel and selective agent BMS-189090 and analogues
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A series of structurally novel small molecule inhibitors of human α-thrombin was prepared to elucidate their structure- activity relationships (SAR), selectivity and activity in vivo. BMS-189090 (5) is identified as a potent, selective, and reversible inh
- Das, Jagabandhu,Kimball,Reid, Joyce A.,Wang, Tammy C.,Lau, Wan F.,Roberts, Daniel G.M.,Seiler, Steven M.,Schumacher, William A.,Ogletree, Martin L.
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- Synthesis and hybridization of novel chiral pyrrolidine based PNA analogue
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Four different PNA fragments containing units of either the R- or S- isomer of N-(2-pyrrolidine-methyl)-N-(thymine-1-acetyl)-glycine (Pmg) were synthesized on a solid support. UV thermal melting experiments with complementary RNAs were performed and it was found that R-Pmg containing PNAs bind better to RNA than those containing the S-Pmg units.
- Slaitas,Yeheskiely
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p. 1377 - 1379
(2007/10/03)
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- Studies on the transformation of azido-group to N-(t-butoxycarbonyl)amino group via Staudinger reaction
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By a simple and direct sequence, treatment of primary azides with tri-n-butylphosphine, followed by addition of di-t-butyl dicarbonate (Boc2O) affords, N-(t-Butoxycarbonyl)amines 2 in moderate to good overall yields. For secondary azides the fo
- Afonso, Carlos A. M.
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p. 261 - 276
(2007/10/03)
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