1148-11-4Relevant articles and documents
The formation of a novel Pd/C-ethylenediamine complex catalyst: Chemoselective hydrogénation without deprotection of the o-benzyl and ZV-Cbz groups
Sajiki, Hironao,Hattori, Kazuyuki,Hirota, Kosaku
, p. 7990 - 7992 (1998)
A Pd/C catalyst formed an isolable complex with ethylenediamine employed as the catalytic poison via one-to-one interaction between Pd metal and ethylenediamine, and this complex catalyst [Pd/ C(en)] chemoselectively hydrogenated a variety of reducible functionalities such as olefin, acetylene, nitro, benzyl ester, and azido in the presence of an O-benzyl or N-Cbz protective group. These findings reinforce the versatility potential of O-benzyl and N-Cbz as protective groups in organic synthesis, and the Pd/C(en) catalyst has been identified as a novel and chemoselective catalyst for the hydrogénation.
Asymmetric aldol reaction organocatalyzed by (S)-proline-containing dipeptides: Improved stereoinduction under solvent-free conditions
Hernandez, Jose G.,Juaristi, Eusebio
, p. 1464 - 1467 (2011)
The organocatalytic activity of the methyl ester of (S)-proline-(S)- phenylalanine, (S,S)-2, in the asymmetric aldol reaction between cyclohexanone and acetone with various aromatic aldehydes under solvent-free conditions in a ball mill has been evaluated. α,α-Dipeptide (S,S)-2 catalyzed the stereoselective formation of the expected aldol products, with higher diastereo-and enantioselectivity relative to similar reactions in solution, up to 91:9 anti:syn diastereomeric ratio and up to 95% enantiomeric excess.(Figure Presented)
Synthesis, antitumor activity, and nephrotoxicity of the optical isomers of 2-aminomethylpyrrolidine(1,1-cyclobutane-dicarboxylato) platinum(II)
Morikawa,Honda,Endoh -i.,Matsumoto,Akamatsu -i.,Mitsui,Koizumi
, p. 837 - 842 (1991)
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.
Microwave spectroscopy of the twist C(β)-exo/C(γ)-endo conformation of prolinamide
Kuhls, Kimberly A.,Centrone, Charla A.,Tubergen, Michael J.
, p. 10194 - 10198 (1998)
The rotational transitions of three isotopomers of prolinamide were measured with a Fourier-transform microwave spectrometer. A twist pyrrolidine ring conformation with C(β)-exo and C(γ)-endo reproduces the experimental moments of inertia. Stark-effect measurements of five [M] components were used to determine that the dipole moment of this conformation of prolinamide is 3.83(4) D. Kraitchman's method of isotopic substitution was used to determine an N-N distance of 2.684(2) A?.
5-(Pyrrolidine-2-yl)tetrazole: Rationale for the increased reactivity of the tetrazole analogue of proline in organocatalyzed aldol reactions
Hartikka, Antti,Arvidsson, Per I.
, p. 4287 - 4295 (2005)
5-[(2S)-Pyrrolidine-2-yl]-1H-tetrazole (1), i.e. the tetrazolic acid analogue of proline, has been found to be significant more reactive than L-proline (2) in various organocatalyzed reactions. In the organocatalyzed direct asymmetric aldol reaction, acetone was reacted with aromatic and aliphatic aldehydes to afford the resulting β-hydroxy ketones in good yields and moderate to high enantiomeric excesses. The increased reactivity of 1, as compared to 2, has been rationalized through a combined computational and NMR spectroscopic study. It was found that catalyst 2 was almost completely engaged in oxazolidinone formation with the aldehyde whereas 1 did not take part in such parasitic equilibrium. This finding, together with the improved solubility of the tetrazole analogue, is proposed to account for the observed reactivity. Wiley-VCH Verlag GmbH & Co. KGaA, 2005.
Synthetic studies towards proline amide isosteres, potentially useful molecules for biological investigations
Takeuchi,Yamada,Suzuki,Koizumi
, p. 225 - 232 (1996)
2-Ethenylpyrrolidine derivative 8b was prepared from N-protected proline ethyl ester 6b. Bromofluorination of 8b wth NBS-Bu4NF/2HF gave a 1:1 regioisomeric mixture, 9b and 10b (X = Br). Dehydrobromination of 9b and 10b with t-BuOK produced a fluoroolefin 11 and a proline amide isostere model 12, respectively. Deprotection of the Z group in 12 was attempted by treatment with CF3COOH. Although formation of the useful molecule is pseudopeptide synthesis, 13, was observed as checked by NMR spectra, it seemed to decompose slowly during purification procedure to give a mixture of fluorine-free compounds.
Organocatalytic activity of α,α-dipeptide derivatives of (S)-proline in the asymmetric aldol reaction in absence of solvent. Evidence for non-covalent π-π Interactions in the transition state
Machuca, Elizabeth,Juaristi, Eusebio
, p. 1144 - 1148 (2015)
The trend in the magnitude of stereoselectivities observed in the asymmetric aldol reaction between cyclohexanone and aromatic aldehydes with varying electron densities, catalyzed by dipeptidic organocatalyst (S,S)-1d, which contains an aromatic naphthyl substituent in the acyclic amino acid residue, is in line with expectation based on π-π stacking interactions between the aromatic ring on the organocatalyst and the aromatic aldehydes. Such non-covalent interactions are apparently enhanced under solvent-free mechanochemical activation in a ball mill.
Rational design of asymmetric organocatalysts - Increased reactivity and solvent scope with a tetrazolic acid
Hartikka, Antti,Arvidsson, Per I.
, p. 1831 - 1834 (2004)
Replacement of the carboxylic acid functionality in the widely used organocatalyst proline with a tetrazolic acid leads to a catalyst with increased reactivity and solvent scope, as demonstrated in the direct catalytic asymmetric aldol reaction.
Pipecolic esters as minimized templates for proteasome inhibition
Giletto, Matthew B.,Osmulski, Pawel A.,Jones, Corey L.,Gaczynska, Maria E.,Tepe, Jetze J.
, p. 2734 - 2746 (2019)
Allosteric regulators of clinically important enzymes are gaining popularity as alternatives to competitive inhibitors. This is also the case for the proteasome, a major intracellular protease and a target of anti-cancer drugs. All clinically used proteasome inhibitors bind to the active sites in catalytic chamber and display a competitive mechanism. Unfortunately, inevitable resistance associated with this type of inhibition drives the search for non-competitive agents. The multisubunit and multicatalytic “proteolytic machine” such as the proteasome is occasionally found to be affected by agents with other primary targets. For example the immunosuppressive agent rapamycin has been shown to allosterically inhibit the proteasome albeit at levels far higher than its mTOR related efficacy. As part of an ongoing program to search for novel proteasome-targeting pharmacophores, we identified the binding domain of rapamycin as required for proteasome inhibition even without the macrocyclic context of the parent compound. By subsequent structure-activity relationship studies, we generated a pipecolic ester derivative compound 3 representing a new class of proteasome inhibitors. Compound 3 affects the core proteasome activities and proliferation of cancer cells with low micromolar/high nanomolar efficacy. Molecular modeling, atomic force microscopy imaging and biochemical data suggest that compound 3 binds into one of intersubunit pockets in the proteasomal α ring and destabilizes the α face and the gate. The α face is used as a docking area for proteasome-regulating protein modules and the gate is critical for controlling access to the catalytic chamber. Thus, the pipecolic ester template elicits a new and attractive mechanism for proteasome inhibition distinct from classical competitive drugs.
The Synthesis of 5,6,7,7a-Tetrahydro-1-methyl-3H-pyrrolizin-3-one by the Palladium-Catalyzed Cyclization of N-Bromoacetyl-2-vinylpyrrolidine
Yang, Shyh-Chyun,Shea, Fang-Rong,Hung, Chung-Wei
, p. 779 - 782 (1998)
N-Bromoacetyl-2-vinylpyrrolidine underwent cyclization to give a pyrrolizidine derivative in the presence of a base and a catalytic amount of palladium catalyst.
