Refernces
10.1002/anie.201900442
The study presents an enantioselective rhodium-catalyzed allylic alkylation of β,γ-unsaturated α-amino nitriles, offering a novel approach to construct β-stereogenic carbonyl derivatives. This method leverages the catalytic asymmetric alkylation of a homoenolate equivalent, addressing the challenge of manipulating three modes of selectivity: regio- and enantioselectivity, as well as geometrical control. The g-stereogenic cyanoenamine products, resulting from the reaction, can be readily hydrolyzed to yield β-substituted carboxylic acids, providing a convenient pathway to various related carbonyl derivatives. The study underscores the critical role of the E-cyanoenamine products' selective formation, facilitated by the chiral rhodium-allyl intermediate, in achieving high enantiocontrol. The methodology not only provides a practical process but also highlights the utility of molecular dynamics simulation in guiding experimental research for the development of small-molecule inhibitors targeting toxic amyloidogenic protein oligomers.
10.1016/j.tetlet.2012.03.030
The research primarily focuses on the development of complementary α-alkylation methods for the synthesis of sterically hindered spiro[pyrazolopyranpiperidine]ketone derivatives, which are potential treatments for type II diabetes. The experiments involve enolate alkylations using DMPU to enhance enolate reactivity and aldol condensations to access a diverse set of derivatives. Key reactants include ketone 2, LiHMDS, DMPU, various alkylating agents, aldehydes, and other reagents like SelectFluor? and Davis' oxaziridine. Analyses utilized include 1H and 13C NMR, IR spectroscopy, and mass spectrometry to characterize the synthesized compounds and confirm the success of the reactions. The study also explores the role of DMPU in enolate formation and reactivity through deuterium experiments, demonstrating its critical role in enhancing enolate reactivity and, in some cases, enolate formation.
10.1016/j.ejmech.2015.09.015
This study focused on the synthesis and antiviral evaluation of dihydropyrimidone and thiopyrimidine derivatives that target HIV integrase, a crucial enzyme in the HIV replication cycle. A series of compounds bearing an aromatic α,γ-diketobutyric acid moiety were synthesized using the Biginelli multicomponent reaction as a key step. The synthesized compounds were evaluated for their ability to inhibit HIV-1 integrase (IN) strand transfer (ST) activity in vitro, with the most active compounds showing nanomolar inhibitory activity. To further understand the interaction mode within the active site of IN, molecular docking analysis was performed using the X-ray crystal structure of IN. The experiments involved the use of various reagents, catalysts, and solvents, and the synthesized compounds were analyzed using techniques such as thin layer chromatography (TLC), column chromatography, NMR spectroscopy, and high-resolution mass spectrometry. Cerium(III) nitrate hexahydrate (Ce(NO3)3.6H2O), lithium hexamethyldisilazide (LiHMDS), and other reagents were used. Biological evaluation included evaluation of enzymatic activity and evaluation of antiviral activity in cellular models. Molecular modeling studies were performed using the Schrodinger Molecular Modeling Suite, and docking simulations were performed to predict the binding mode of the compounds within the HIV integrase active site.
10.1246/bcsj.69.221
The study explores the synthesis of 10-cyanoverticillene (8) as a key intermediate in the pursuit of verticillols. The researchers utilized geranyl cyanide (3) and allyl chloride (4) as starting materials, coupling them with SnCl4 to form axial and equatorial chlorides (6a and 6b). Through dehydrochlorination of these chlorides with LiCl in DMF, they obtained cyano ester (9) and other derivatives. The cyano ester (9) was then converted to cyano chloride (7), which underwent C-C bond formation with lithium bis(trimethylsilyl)amide to yield 10-cyanoverticillene (8). The study also involved selective oxidation of the tetrasubstituted double bond in 8 to produce epoxy-verticillene derivatives (15 and 16), and attempted hydride reduction of these epoxides under various conditions, leading to unexpected results such as dehydroxymethylation. Additionally, the synthesis of dl-verticillene (13) was achieved through reduction and deformylation reactions. The study provides insights into the synthesis of verticillols and the reactivity of the synthesized compounds.
10.1016/j.tetlet.2011.07.078
The research focuses on the stereoselective synthesis of the peptide moiety of jamaicamides, which are marine natural products with sodium channel blocking properties. The synthesis begins with natural amino acids, L-alanine and N-Boc-β-alanine, and utilizes Meldrum's acid as a key reactant. The researchers detail the preparation of two segments of the peptide: the pyrrolidone ring and the N-Boc-β-methoxy enone carboxylic acid. Various reagents such as EDC·HCl, DMAP, NaBH4, and LiHMDS are used in a series of reactions including condensation, reduction, and amide bond formation. Analytical techniques likely employed, though not explicitly mentioned in the paragraph, include NMR spectroscopy and mass spectrometry for compound characterization. The study also discusses alternative routes and yields for different steps, aiming to optimize the synthesis process.
10.1021/jo801665k
The research focuses on the π-facial stereoselective alkylation of chiral bicyclic lactams, specifically examining the reversal of diastereoselectivity in the benzyl bromide alkylation of phenylglycinol-derived oxazolopiperidone enolates. The study employs a combination of theoretical calculations and experimental assays to explore this reversal, attributing it to the formation of a C-H···π hydrogen bond between the C-H unit of the C8a angular position and the benzene ring of the alkylating reagent. The experiments involve the generation of enolates from chiral bicyclic lactams using lithium bis(trimethylsilyl)amide as the base, followed by the addition of alkylating reagents such as benzyl bromide. The reaction products are analyzed using techniques like gas chromatography/mass spectrometry (GC/MS), infrared (IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and high-resolution mass spectrometry (HRMS) to determine the diastereoisomeric ratios and confirm the structures of the products. The research provides valuable insights into the factors influencing diastereoselectivity in alkylation reactions, which is crucial for the selective preparation of enantiopure bioorganic and pharmaceutical compounds.
10.1002/anie.201201874
The research focuses on the development of a novel and potentially powerful dual catalyst cycle for the enantioselective functionalization of weakly acidic benzylic C-H groups. The purpose of this study was to achieve asymmetric cross-coupling of aryl triflates to the benzylic position of benzylamines, a process that is particularly challenging due to the difficulty in arylating certain types of C-H bonds and the need for enantioselectivity. The researchers envisioned a dual catalyst cycle involving a palladium-catalyzed cross-coupling and a reversible deprotonation of activated benzylic CH groups. They separated the development into three phases, with the first phase focusing on the palladium-catalyzed cycle using an arene-activating moiety, {Cr(CO)3}, which would not undergo arene exchange. The project's current phase introduced an enantioselective version of the reaction, which proceeds through an unusual dynamic kinetic resolution (DKR). The chemicals used in this process include [(h6-benzylamine)Cr(CO)3] complexes, aryl triflates, LiN(SiMe3)2, and a variety of enantioenriched phosphine ligands, with Cy-Mandyphos-based palladium catalysts showing the highest enantioselectivity. The conclusions drawn from the research indicate that diastereoselective transmetallation of one enantiomer of a rapidly equilibrating planar-chiral secondary benzyllithium species is likely the enantioselectivity-determining step in this process. The approach represents a novel disconnection for the synthesis of enantioenriched diarylmethylamines, which are core structures in several pharmaceuticals, and while the chemistry does not yet constitute a practical synthesis, the strategy and conceptual understanding gained are critical for future development of dual catalyst enantioselective functionalization of weakly acidic C-H bonds.
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