- Mechanistic implications of the enantioselective addition of alkylzinc reagents to aldehydes catalyzed by nickel complexes with α-amino amide ligands
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The enantioselective alkylation of aldehydes catalysed by nickel(ii)-complexes derived from α-amino amides was studied by means of density functional theory (DFT) and ONIOM (B3LYP:UFF) calculations. A mechanism was proposed in order to investigate the origin of enantioselectivity. The chirality-determining step for the alkylation was the formation of the intermediate complexes with the involvement of a 5/4/4-fused tricyclic transition state. The predominant products predicted theoretically were of (S)-configuration, in good agreement with experimental observations. The scope of the reaction was examined and high yields and enantioselectivities were observed for the enantioselective addition of Et2Zn and Me2Zn to aromatic and aliphatic aldehydes.
- Escorihuela, Jorge,Burguete, M. Isabel,Ujaque, Gregori,Lledós, Agustí,Luis, Santiago V.
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p. 11125 - 11136
(2016/12/07)
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- Amides in one pot from Carboxylic Acids and Amines via Sulfinylamides
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An efficient method has been developed for the direct amidification of carboxylic acids via sulfinylamides preformed in situ by the reaction of pure amines with prop-2- ene-1-sulfinyl chloride. The method can be applied to aliphatic acids, including pivalic acid, aromatic acids, and primary and secondary amines. It is compatible with acids bearing unprotected alcohol, phenol, and ketone moieties and applicable to the synthesis of peptides. It does not induce their a-epimerization.
- Bai, Jianfei,Zambron, Bartosz K.,Vogel, Pierre
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supporting information
p. 604 - 607
(2014/04/03)
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- Organocatalysis of asymmetric aldol reaction in water: Comparison of catalytic properties of (S)-valine and (S)-proline amides
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(S)-Valine amides containing (S)- or (R)-α-phenylethyl substituents at N1 atom efficiently catalyze asymmetric aldol reactions between cyclic (heterocyclic) ketones and aromatic aldehydes in water, predominantly giving rise to the aldol anti-di
- Kucherenko,Siyutkin,Dashkin,Zlotin
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p. 1010 - 1015
(2014/03/21)
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- C2 symmetrical nickel complexes derived from α-amino amides as efficient catalysts for the enantioselective addition of dialkylzinc reagents to aldehydes
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A series of C2 symmetrical 1:2 Ni:L complexes derived from α-amino amides were studied for the enantioselective addition of dialkylzinc reagents to aldehydes. Different structural elements on the ligands seem to play an important role in determining the observed enantioselectivity. Through optimization of structure and reaction conditions, the best ligand provided secondary alcohols in excellent yields (up to 98%) and enantioselectivity of up to 99% ee for (R)-enantiomer. A transition state model has been proposed to explain the observed enantioselectivities based on computational calculations at the DFT level. Very interestingly, calculations suggest a coordination model of the aldehyde to the metal complex through association of a lone pair of the carbonyl oxygen to the hydrogen atom of an amino group.
- Escorihuela, Jorge,Altava, Belen,Burguete, M. Isabel,Luis, Santiago V.
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p. 551 - 558
(2013/07/27)
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- Catalyst and solvent-free amidation of inactive esters of N-protected amino acids
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A catalyst free procedure for the preparation of amides from inactive esters of N-protected amino acids and various amines is demonstrated under mild reaction conditions. Our effort to recover excess amine and generated alcohol is an approach towards environment friendly and cost effective synthesis under easy operational conditions.
- Nadimpally, Krishna Chaitanya,Thalluri, Kishore,Palakurthy, Nani Babu,Saha, Abhijit,Mandal, Bhubaneswar
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supporting information; experimental part
p. 2579 - 2582
(2011/06/21)
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- Synthesis and evaluation of pseudopeptidic fluorescence pH probes for acidic cellular organelles: In vivo monitoring of bacterial phagocytosis by multiparametric flow cytometry
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A new family of fluorescent anthracenic pH probes has been synthesized, chemically characterized, and their photophysical properties have been investigated by steady-state and time-resolved fluorescence spectroscopy. The ability of these compounds to monitor pH has been investigated in solution and it was found that molecules 1-12 can act as fluorescent sensors for pH in a range between 4.6 and 6.5. This range corresponds to the pH of acidic organelles in the cell (pH 4.5-6.0) for which a limited number of probes are described. The acid-base behavior of each sensor varies slightly depending on the nature of substituents close to the amines present in the molecules. Thus, the pK a of this family of compounds can be finely tuned by the appropriate selection of the synthetic building blocks at the design stage. To test the potential diagnostic applications of this family of probes, macrocyclic pseudopeptide 2 was used to monitor the phagocytosis of a culture of GFP-labelled bacteria by human monocytic cells U937 using flow cytometry as the analytical tool. It was found that the occurrence of bacterial killing was concomitant with the production of reactive oxygen species and a drop in pH, the latter monitored indirectly by macrocyclic sensor 2, which suggests its potential use for diagnostic purposes. A new family of anthracenic macrocycles has been synthesized that can act as fluorescent probes for pH in the range 4.6-6.5. The pKa values of these compounds can be finely tuned. In flow cytometry experiments, it was found that bacterial killing by human monocytes (U937) occurred with a simultaneous drop in pH, which was monitored by one of the macrocyclic sensors.
- Burguete, M. Isabel,Galindo, Francisco,Izquierdo, M. Angeles,O'Connor, Jose-Enrique,Herrera, Guadalupe,Luis, Santiago V.,Vigara, Laura
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supporting information; experimental part
p. 5967 - 5979
(2011/02/26)
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- Inhibitors of tripeptidyl peptidase II. 2. Generation of the first novel lead inhibitor of cholecystokinin-8-inactivating peptidase: A strategy for the design of peptidase inhibitors
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The cholecystokinin-8 (CCK-8)-inactivating peptidase is a serine peptidase which has been shown to be a membrane-bound isoform of tripeptidyl peptidase II (EC 3.4.14.10). It cleaves the neurotransmitter CCK-8 sulfate at the Met-Gly bond to give Asp-Tyr(SO3H)-Met-OH + Gly-Trp-Met-Asp-Phe-NH2. In seeking a reversible inhibitor of this peptidase, the enzymatic binding subsites were characterized using a fluorimetric assay based on the hydrolysis of the artificial substrate Ala-Ala-Phe-amidomethylcoumarin. A series of di- and tripeptides having various alkyl or aryl side chains was studied to determine the accessible volume for binding and to probe the potential for hydrophobic interactions. From this initial study the tripeptides Ile-Pro-Ile-OH (K(i) = 1 μM) and Ala-Pro-Ala-OH (K(i) = 3 μM) and dipeptide amide Val-Nvl-NHBu (K(i) = 3 μM) emerged as leads. Comparison of these structures led to the synthesis of Val-Pro-NHBu (K(i) = 0.57 μM) which served for later optimization in the design of butabindide, a potent reversible competitive and selective inhibitor of the CCK-8-inactivating peptidase. The strategy for this work is explicitly described since it illustrates a possible general approach for peptidase inhibitor design.
- Ganellin, C. Robin,Bishop, Paul B.,Bambal, Ramesh B.,Chan, Suzanne M. T.,Law, James K.,Marabout, Benoit,Luthra, Pratibha Mehta,Moore, Andrew N. J.,Peschard, Olivier,Bourgeat, Pierre,Rose, Christiane,Vargas, Froylan,Schwartz, Jean-Charles
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p. 664 - 674
(2007/10/03)
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- Peptide-titanium complex as catalyst for asymmetric addition of hydrogen cyanide to aldehyde
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The complex of titanium ethoxide and an acyclic dipeptide ester whose terminal amino group is modified to a salicylal-type Schiff base catalyzes the asymmetric addition of hydrogen cyanide to aldehydes with high enantioselectivity. In the reaction of benzaldehyde and hydrogen cyanide, (R)-mandelonitrile is obtained with an enantiomeric excess of 90% when N-((2-hydroxy-1-naphthyl)methylene)-(S)-valyl-(S)-tryptophan methyl ester is employed. In place of the dipeptide, the amide derivatives of an amino acid modified by substituted salicylaldehyde, such as N-(3,5-dibromosalicylidene)-(S)-valine piperidide, exhibit an entirely opposite stereoselectivity to yield S-cyanohydrins with optical purities up to 97% ee. This novel peptide-titanium complex, therefore, enables us to afford optically active cyanohydrins of both absolute configurations by using natural S-amino acids as chiral auxiliaries.
- Nitta, Hideaki,Yu, Donghai,Kudo, Masanobu,Mori, Atsunori,Inoue, Shohei
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p. 7969 - 7975
(2007/10/02)
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- N,N'-Bis(2-oxo-3-oxazolidinyl)phosphorodiamidic Azide: A Useful Coupling Agent in Peptide Synthesis
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N,N'-Bis(2-oxo-3-oxazolidinyl)phosphorodiamidic azide (BOPA), has been developed as an efficient coupling reagent in peptide synthesis.Coupling reaction proceeds smoothly with no detectable racemization.
- Katti, S. B.,Misra, P. K.,Haq, W.,Mathur, K. B.
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