- Basicities and Nucleophilicities of Pyrrolidines and Imidazolidinones Used as Organocatalysts
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The Br?nsted basicities pKaH (i.e., pKa of the conjugate acids) of 32 pyrrolidines and imidazolidinones, commonly used in organocatalytic reactions, have been determined photometrically in acetonitrile solution using CH acids as indicators. Most investigated pyrrolidines have basicities in the range 16 aH aH aH 12.6) and the 2-imidazoliummethyl-substituted pyrrolidine A21 (pKaH 11.1) are outside the typical range for pyrrolidines with basicities comparable to those of imidazolidinones. Kinetics of the reactions of these 32 organocatalysts with benzhydrylium ions (Ar2CH+) and structurally related quinone methides, common reference electrophiles for quantifying nucleophilic reactivities, have been measured photometrically. Most reactions followed second-order kinetics, first order in amine and first order in electrophile. More complex kinetics were observed for the reactions of imidazolidinones and several pyrrolidines carrying bulky 2-substituents, due to reversibility of the initial attack of the amines at the electrophiles followed by rate-determining deprotonation of the intermediate ammonium ions. In the presence of 2,4,6-collidine or 2,6-di-tert-butyl-4-methyl-pyridine, the deprotonation of the initial adducts became faster, which allowed the rate of the attack of the amines at the electrophiles to be determined. The resulting second-order rate constants k2 followed the correlation log?k2(20 °C) = sN(N + E), where electrophiles are characterized by one parameter (E) and nucleophiles are characterized by the two solvent-dependent parameters N and sN. In this way, the organocatalysts A1-A32 were integrated in our comprehensive nucleophilicity scale, which compares n-, -, and σ-nucleophiles. The nucleophilic reactivities of the title compounds correlate only poorly with their Br?nsted basicities.
- An, Feng,Maji, Biplab,Min, Elizabeth,Ofial, Armin R.,Mayr, Herbert
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supporting information
p. 1526 - 1547
(2020/02/04)
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- D -Prolyl-2-(trifluoromethylsulfonamidopropyl)pyrrolidine: An Organocatalyst for Asymmetric Michael Addition of Aldehydes to β-Nitroalkenes at Ambient Conditions
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Four 2-(trifluoromethylsulfonamidoalkyl)pyrrolidines and their d-prolinamides were prepared and screened as organocatalysts for the Michael addition reaction of aldehydes with β-nitroalkenes at rt and without the use of additives. d-Prolyl-2-(trifluoromet
- Gorde, Amol B.,Ramapanicker, Ramesh
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p. 1523 - 1533
(2019/02/07)
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- Enantioselective Synthesis of 2-Aminomethyl and 3-Amino Pyrrolidines and Piperidines through 1,2-Diamination of Aldehydes
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An efficient method for the synthesis of 1,2-diamines from aldehydes through proline-catalyzed asymmetric α-amination followed by reductive amination is reported. The products resemble those obtained through direct asymmetric diamination of terminal alkenes. The methodology is used to synthesize 2-aminomethyl and 3-amino pyrrolidines and piperidines in high yields and with a good enantioselectivity. The usefulness of the method is demonstrated through the synthesis of a 2-aminomethyl iminocyclitol.
- Ansari, Anas,Ramapanicker, Ramesh
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p. 8161 - 8169
(2018/07/25)
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- Corresponding amine nitrile and method of manufacturing thereof
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The invention relates to a manufacturing method of nitrile. Compared with the prior art, the manufacturing method has the characteristics of significantly reduced using amount of an ammonia source, low environmental pressure, low energy consumption, low production cost, high purity and yield of a nitrile product and the like, and nitrile with a more complex structure can be obtained. The invention also relates to a method for manufacturing corresponding amine from nitrile.
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Paragraph 0238
(2017/10/22)
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- Biomimetic asymmetric Michael addition reactions in water catalyzed by amino-containing β-cyclodextrin derivatives
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Nine β-cyclodextrin derivatives containing an amino group were synthesized via nucleophilic substitution from mono(6-O-p-tolylsulfonyl)-β-cyclodextrin and used in asymmetric biomimetic Michael addition reactions in water at room temperature. The mechanism responsible for the moderate activity and enantioselectivity of the β-cyclodextrin derivatives was explored using nuclear magnetic resonance spectroscopy, namely 2D 1H rotating-frame overhauser effect spectroscopy (ROESY), ultraviolet absorption spectroscopy, and quantum chemical calculations, which provide a useful technique for investigating the formation of inclusion complexes. The effects of the pH of the reaction medium, the β-cyclodextrin derivative dosage, the structure of the modifying amino group, and various substrates on the yield and enantioselectivity were investigated. The results indicated that these factors had an important effect on the enantiomeric excess (ee) in the reaction system. Experiments using a competitor for inclusion complex formation showed that a hydrophobic cavity is necessary for enantioselective Michael addition. A comparison of the reactions using 4-nitro-β-nitrostyrene and 2-nitro-β-nitrostyrene showed that steric hindrance improved the enantioselectivity. This was verified by the optimized geometries obtained from quantum chemical calculations. An ee of 71% was obtained in the asymmetric Michael addition of cyclohexanone and 2-nitro-β-nitrostyrene, using (S)-2-aminomethylpyrrolidine-modified β-CD as the catalyst, in an aqueous buffer solution, i.e., CH3COONa-HCl (pH 7.5).
- Zhu, Qingying,Shen, Haimin,Yang, Zhujin,Ji, Hongbing
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p. 1227 - 1234
(2016/09/07)
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- Transfer hydrogenation reactions catalyzed by chiral half-sandwich Ruthenium complexes derived from Proline
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Chiral ruthenium half-sandwich complexes were prepared using a chelating diamine made from proline with a phenyl, ethyl, or benzyl group, instead of hydrogen on one of the coordinating arms. Three of these complexes were obtained as single diastereoisomers and their configuration identified by X-ray crystallography. The complexes are recyclable catalysts for the reduction of ketones to chiral alcohols in water. A ruthenium hydride species is identified as the active species by NMR spectroscopy and isotopic labelling experiments. Maximum enantio-selectivity was attained when a phenyl group was directly attached to the primary amine on the diamine ligand derived from proline. [Figure not available: see fulltext.]
- Pandia Kumar, Arun Kumar,Samuelson, Ashoka G
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p. 1405 - 1415
(2016/09/19)
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- Biomimetic asymmetric aldol reactions catalyzed by proline derivatives attached to β-cyclodextrin in water
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Two proline derivatives, (S)-2-aminomethylpyrrolidine and (R)-2-aminomethylpyrrolidine modified β-CD (CD-1, CD-2) were synthesized in the yields of 31% and 14%. Their self-inclusion conformations were characterized by 1H ROESY NMR studies and q
- Shen, Hai-Min,Ji, Hong-Bing
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supporting information; experimental part
p. 3541 - 3545
(2012/09/08)
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- Synthesis, characterisation and in vitro cytotoxicity studies of a series of chiral platinum(II) complexes based on the 2-aminomethylpyrrolidine ligand: X-ray crystal structure of [PtCl2(R-dimepyrr)] (R-dimepyrr = N-dimethyl-2(R)-aminomethylpyrrolidine)
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A series of platinum(II) complexes were synthesised based on the enantiomerically pure amino acid proline. Novel synthetic pathways were developed, adapted from standard peptide chemistry, to produce the 2-aminomethylpyrrolidine (pyrr) ligand and its derivatives with differing arrangements of methyl substituents at the exocyclic amine sites. The crystal structure of [PtCl2(R-dimepyrr)] (R-dimepyrr = N,N-dimethyl-2(R)-aminomethylpyrrolidine) is reported and the five-membered ligand ring has been shown to be in an envelope conformation. Cytotoxicity studies were carried out on the ovarian cancer A2780 tumour cell line and its cisplatin-resistant variant, A2780cisR. Remarkably good activity was seen for several of the drugs when compared to cisplatin despite the addition of substantial steric bulk to the amine groups, and there was a lack of cross-resistance with cisplatin seen for some compounds.
- Diakos, Connie I.,Zhang, Mei,Beale, Philip J.,Fenton, Ronald R.,Hambley, Trevor W.
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experimental part
p. 2807 - 2814
(2009/10/10)
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- CHEMICAL COMPOUNDS
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The present invention relates generally to novel therapeutic compounds and AXOR 109 agonists, and processes for the manufacture and use of the same.
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Page/Page column 81-82
(2008/06/13)
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- POLYCYCLIC CARBAMOYLPYRIDONE DERIVATIVE HAVING HIV INTEGRASE INHIBITORY ACTIVITY
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The present invention is to provide a novel compound (I), having the anti-virus activity, particularly the HIV integrase inhibitory activity, and a drug containing the same, particularly an anti-HIV drug, as well as a process and an intermediate thereof. Compound (I) wherein Z1 is NR4; R1 is hydrogen or lower alkyl; X is a single bond, a hetero atom group selected from O, S, SO, SO2 and NH, or lower alkylene or lower alkenylene in which the hetero atom group may intervene; R2 is optionally substituted aryl; R3 is hydrogen, a halogen, hydroxy, optionally substituted lower alkyl etc; and R4 and Z2 part taken together forms a ring, to form a polycyclic compound, including e.g., a tricyclic or tetracyclic compound.
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Page/Page column 136
(2010/11/24)
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- Synthesis, antitumor activity, and nephrotoxicity of the optical isomers of 2-aminomethylpyrrolidine(1,1-cyclobutane-dicarboxylato) platinum(II)
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The optical isomers of 2-aminomethylpyrrolidine(1,1-cyclobutane-dicarboxylato)platinum(II) (DWA2114, 1), which has potent antitumor activity against various tumors, were synthesized. They were examined for antitumor activity against Colon 26 carcinoma in a sc-iv system, and changes in urinary protein and sugar levels in drug-treated mice were used as an index of nephrotoxicity. In their effect on tumors, (+)-(S)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato) platinum(II) (6b) was more potent than the enantiomer 6a in that the effective dose of 6b was smaller than that of 6a; but, both drugs exhibited potent antitumor activity. On the other hand, a distinct difference between 6a and 6b was shown in their nephrotoxicity. Isomer 6b induced a great increase in urinary protein and sugar levels in mice, whereas 6a caused no increase in these levels.
- Morikawa,Honda,Endoh -i.,Matsumoto,Akamatsu -i.,Mitsui,Koizumi
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p. 837 - 842
(2007/10/02)
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- TRANSITION METAL COMPLEXES - A NEW CLASS OF CATALYSTS OF INTERFACIAL ALKYLATION FOR THE ASYMMETRICAL SYNTHESIS OF α-AMINO ACIDS
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A new class of catalysts of interfacial asymmetrical alkylation is suggested for the synthesis of α-amino acids - positively charged complexes of the transition metals Cu(II), Ni(II), and Pd(II).These complexes consist of several fragments, by variation of which the structure of the catalysts can readily be modified.The complexes are chiral on account of (S)proline derivatives contained in them as one of the fragments.The catalyst complexes (C) were used in alkylation of amino acid fragments of Ni(II) complexes of the Schiff base of glycine with N-(2-pyridinecarbonyl)-o-aminobenzophenone (Ni-PBP-Gly) and the Schiff base of alanine with N-(2-pyridinecarbonyl)-o-aminobenzaldehyde (Ni-PBA-Ala) under interfacial conditions.After decomposition of alkylated complexes, phenylalanine and α-methyl-phenylalanine were isolated with yields of 33-87percent and optical purity (o. p.) from 3 to 21percent, depending on the C used.
- Belokon', Yu. N.,Maleev, V. I.,Videnskaya, S. O.,Saporovskaya, M. B.,Tsyryapkin, V. A.,Belikov, V. M.
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p. 110 - 118
(2007/10/02)
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- N-heterocyclic platinum complexes
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Novel platinum complexes represented by the formula: STR1 wherein A is alkylene having carbon atoms of from 1 to 3; R1, R2, R3 and R4 are the same or different and are hydrogen or alkyl having carbon atoms of from 1 to 4; X and Y are independently a halogen atom, or combined together to form STR2 and l, m and n are independently 0 or 1, and a process for preparing the same are disclosed. These platinum complexes have high antitumor activity and low toxicity, and are easily soluble in water. Therefore, they are very useful as an antitumor agent.
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- Potential Neuroleptic Agents. 2,6-Dialkoxybenzamide Derivatives with Potent Dopamine Receptor Blocking Activities
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A series of some novel N-(1-ethyl-2-pyrrolidinylmethyl)benzamides was synthesized and tested for dopamine receptor blockade in vivo by the ability to block the apomorphine syndrome in the rat.Several compounds were considerably more potent than sulpiride as dopamine receptor blockers and displayed low liability to induce extrapyramidal side effects (catalepsy) in the rat.The blockade of dopamine receptor activity in vivo was mainly confined to the levorotatory isomers having the S absolute configuration.The structure-activity relationships are discussed.
- Florvall, Lennart,Oegren, Sven-Ove
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p. 1280 - 1286
(2007/10/02)
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