10.1021/ol900893e
The study focuses on the enantioselective organocatalytic conjugate reduction of α-azole-containing α,β-unsaturated aldehydes, achieving good yields and high optical purity (up to 94%) in the products. The process was applied to the synthesis of the C7-C14 fragment of ulapualide A, a natural product with potential antitumor activity. Key chemicals used include chiral organocatalysts derived from (S)-proline, imidazolidinone-type catalysts, and Hantzsch esters as hydride donors. These reagents served to catalyze the enantioselective reduction of the α,β-unsaturated aldehydes, a transformation that is significant for accessing biologically valuable molecules like ulapualide A. The study also explored the impact of different ester moieties, solvents, and counterions on the reaction's selectivity and efficiency.
10.1016/S0040-4039(02)00632-9
The research investigates the stereoretentive C-C bond formations in aldol cyclisations of 1-(3-oxobutyryl) derivatives of L-4-oxaproline and L-proline isopropyl esters. The purpose of the study was to explore the possibility of simplifying the self-generation of stereocenters in the synthesis of β-C-substituted β-amino acids, a class of compounds with wide-ranging biological properties, by leveraging the chirality memory effects observed in enolate intermediates. The researchers concluded that the aldol cyclisations conducted on oxaproline and proline scaffolds demonstrated significant retention of configuration, extending the scope of stereoinductions attributable to axially chiral enolate intermediates. Key chemicals used in the process included L-serine, isopropyl esters, L-oxaproline, L-proline, diketene, triethylamine, and potassium cyanide, among others. The study's findings are significant as they provide insights into the role of axially chiral enolate intermediates in stereoselective synthesis and contribute to the development of more efficient methods for producing enantioenriched β-C-substituted β-amino acids embedded in heterocyclic frameworks.
10.1039/b926498a
The study investigates the highly efficient chemoselective construction of 2,2-dimethyl-6-substituted 4-piperidones via a multi-component tandem Mannich reaction in ionic liquids. The room temperature ionic liquid [bmim][PF6] serves as an efficient and recyclable medium for this reaction. L-proline acts as a catalyst to enhance the chemoselectivity of the reaction. Ammonia, aldehydes, and acetone are the main reactants. The reaction involves a tandem Mannich reaction of these reactants in the presence of L-proline in [bmim][PF6]. The study explores the optimization of reaction conditions using different solvents and catalysts, and examines the scope of the reaction with various aldehydes as substrates. The results show that aryl, heteroaromatic, and aliphatic aldehydes can all undergo effective tandem Mannich reactions to produce the desired 2,2-dimethyl-6-substituted 4-piperidones in moderate to good yields. The ionic liquid and catalyst system can be recycled for multiple reaction cycles, making this method potentially useful for industrial applications.
10.1002/chem.200600725
The research focuses on the development of a direct catalytic asymmetric a-aminomethylation of aldehydes, a significant advancement in organic chemistry. This reaction provides a pathway to ?-amino aldehydes, which are valuable precursors to ?2-amino acid derivatives and ?-amino alcohols, important in pharmaceuticals. The study explores the use of chiral amine and amino acid catalysts to facilitate the reaction between unmodified aldehydes and a formaldehyde-derived imine precursor. The reactions were conducted under various conditions, with the addition of lithium halide salts found to enhance enantioselectivity. The experiments involved screening different catalysts, such as proline and its derivatives, as well as chiral pyrrolidines, using dibenzylamine-derived aminomethyl ether and isovaleraldehyde as reactants. The enantioselectivity and conversion rates were determined through NMR spectroscopic analyses and chiral-phase HPLC analysis. The results showed that the reactions were fast, highly chemoselective, and yielded the corresponding ?-amino alcohols with high enantiomeric excess (up to 98% ee) after in situ reduction. The research also proposed transition-state models to account for the stereochemical outcomes of the reactions catalyzed by different chiral pyrrolidines and proline derivatives.
10.1007/s11172-010-0186-0
The research focuses on the kinetics of the arenesulfonylation reaction involving DL-serine, L-proline, DL-threonine, and DL-methionine with 3-nitrobenzenesulfonyl chloride (3-NBSC) in mixed solvent systems of 1,4-dioxane—water and propan-2-ol—water. The study was conducted spectrophotometrically at 298 K to determine the reaction rate constants and understand the reactive forms of the amino acids. The main reactive form was found to be anionic, and the basicity of the α-amino acids was identified as a crucial factor in determining the reaction rate. The rate constants for arenesulfonylation were compared with those of N-acylation with benzoyl chloride and reactions with benzoic acid 4-nitrophenyl ester. The experiments involved monitoring the reaction's progress by tracking changes in 3-NBBSC concentration at 242 nm using a spectrophotometer. The reaction conditions, including pH, were controlled using an acetate buffer, and the pH was measured with an ionomer. The research aimed to optimize synthetic conditions for sulfamides, which are important due to their role in enzyme inhibition and as protective groups in organic synthesis.
10.1016/j.bmcl.2005.03.077
The study focused on the design and evaluation of a novel series of DPP-IV inhibitors, specifically 1-(c-substituted prolyl)-(S)-2-cyanopyrrolidines, based on the predicted binding mode of the known DPP-IV inhibitor NVP-DPP728. The aim was to develop potent inhibitors that could potentially serve as a new type of anti-diabetic agent by potentiating and extending the action of glucagon-like peptide-1 (GLP-1), which stimulates insulin secretion in response to meal ingestion. The researchers synthesized and tested various derivatives with different substituents at the c-position of the proline moiety to determine their inhibitory activity against DPP-IV. Key chemicals used in the study included NVP-DPP728 as a reference inhibitor, (S)-2-cyanopyrrolidine as a proline mimic, and various c-substituted proline derivatives with different functional groups. The purpose of these chemicals was to create conformationally constrained analogs that could interact with the S2 pocket of DPP-IV, thereby exhibiting more potent inhibitory activity. The study revealed that compounds with (S)-stereochemistry at the c-position were more potent than their (R)-isomers, with the (3,4-dicyanophenyl)amino- and (3-chloro-4-cyanophenyl)amino-derivatives showing the highest inhibitory activity.
10.1021/jm0612158
The study investigates the development of a new series of spirodiketopiperazine derivatives for their cytotoxic potential against various human tumor cell lines. The researchers synthesized these compounds by condensing the 3-amino-3(ethoxycarbonyl)-2,3-dihydrothieno[2,3-b]naphtho-4,9-dione system with various amino acids, followed by intramolecular lactamization. The study evaluated the cytotoxic activity of these derivatives against MCF-7 human breast carcinoma and SW 620 human colon carcinoma cell lines, revealing that certain isomers derived from Proline (Pro), Cysteine (Cys), and Methionine (Met) exhibited cytotoxic potency comparable to or greater than that of doxorubicin. The study also explored the topoisomerase II inhibition activity and DNA-binding properties of these compounds. The results suggest that these derivatives could potentially circumvent multiple-drug resistance mechanisms and have significant cytotoxic effects on various tumor cell lines, including those resistant to doxorubicin and cisplatin.
10.1007/BF00962755
The study investigates the fluorodeoxygenation of (R,S)- and (S)-proline using sulfur tetrafluoride in hydrogen fluoride to produce =-trifluoromethylpyrrolidine (-)-(I), aiming to explore the retention of optical activity and absolute configuration of the chiral =-carbon atom during this process. The authors obtained diastereomeric derivatives such as (+)-(IIA) to determine the optical purity of (-)-(I), which was found to be no less than 96%. The study also examines the stereochemistry of chromophoric derivatives like the nitrosoamine (+)-(III) and the chloroamine (-)-(IV), comparing their chiroptical characteristics with those of analogs such as l-nitroso-(S)-proline methyl ester (V) and l-chloro-(S)-proline methyl ester (VI). The results indicate that the absolute (S) configuration of the carbon chiral center is preserved during the fluorodeoxygenation of (S)-proline.
Xn,
Xi
