10.1124/jpet.120.000266
The research aims to investigate the mechanism by which a novel chemical compound, SF-3-030, selectively targets and inhibits the proliferation of melanoma cells with constitutively active ERK1/2 signaling, such as those harboring the BRAF V600E mutation. The study reveals that SF-3-030 interacts with ERK2, forming a covalent adduct on cysteine 252, which is near the docking site for substrate recruitment. This interaction leads to rapid changes in immediate early gene levels, particularly those containing the DEF motif, and induces an oxidative stress response, which is associated with the inhibition of melanoma cell proliferation. The research concludes that SF-3-030's mechanism of action is ROS-dependent but independent of NRF2, suggesting a potential therapeutic approach for melanoma treatment. Key chemicals used in the study include SF-3-030, ERK2, and various ROS inhibitors such as N-acetyl cysteine (NAC), sodium pyruvate, and mannitol.
10.1039/b000269k
The research focuses on the preparation of chiral enantiopure 2-(hydroxyalkyl)pyridine derivatives, which are valuable in asymmetric catalysis. The experiments utilize naturally occurring chiral compounds such as D-mannitol, L-lactic acid, and L-mandelic acid as starting materials. Key reactants include 2-lithiopyridine, (R)-2,3-O-isopropylideneglyceraldehyde, and various esters derived from the aforementioned chiral compounds. The methodology involves the synthesis of 2-(1-hydroxyalkyl)pyridines and 6,6'-bis(1-hydroxyalkyl)-2,2'-bipyridines through a series of reactions, including lithiation, reduction with sodium borohydride, and nickel-catalyzed coupling. The analyses used to determine the success of the syntheses and the structures of the products encompass NMR spectroscopy (both 1H and 13C), optical rotation measurements, and in some cases, the preparation and analysis of Mosher's esters to determine the absolute configurations of the synthesized chiral alcohols.
10.1021/jo0206824
The research focuses on the total syntheses of symbioramide derivatives, which are bioactive compounds with potential antileukemic properties, derived from L-serine. The study involves the preparation of various symbioramide derivatives, including (2S,3R,2′R,3′E)-N-(2′-hydroxy-3′-octadecenoyl)-dihydrosphingosine (1a) and its diastereomers (1b-d), by synthesizing the amino part (D-erythro-dihydrosphingosine) and acid parts ((2R,3E)-2-hydroxy-3-octadecenoic acid and its isomers) from L-serine and D-mannitol, respectively. The synthesized compounds were then assessed for their antileukemic activities against HL-60 and L-1210 cell lines using the MTT assay. The experiments utilized various reagents, protection and deprotection strategies, and purification techniques such as column chromatography. Analytical methods like specific rotation measurements, infrared spectroscopy (IR), nuclear magnetic resonance (NMR), and high-resolution mass spectrometry (HRMS) were employed to characterize the synthesized compounds and assess their structures and purities. The results indicated that all symbioramide derivatives showed moderate antileukemic activities against L-1210 cells, with compound 1d being the most effective.
10.1016/j.tetlet.2008.10.092
The research focuses on the enantioselective synthesis of (S)-3,7-dimethyl-2-oxo-6-octene-1,3-diol, a pheromone of the Colorado potato beetle, which is a significant pest causing substantial agricultural damage. The study presents a novel synthetic approach that yields the pheromone in seven steps with an overall yield of 46.54% and 98.6% enantiomeric purity. Key reactants include mannitol as the starting material, aldehyde 1, (4-methylpent-3-enyl)-magnesium bromide for the Grignard reaction, PCC for oxidation to ketone 3, and a combination of MeLi and SnCl4 for stereoselective methylation to produce the key intermediate tertiary alcohol 4. The synthesis also involves PPTS in methanol for acetonide protection cleavage, TBDPSCl for selective protection of the primary hydroxyl group, and Swern oxidation for the oxidation step. Analyses used to determine the isomeric and enantiomeric purity include chiral GC analysis. The research also explores the production of analogues to study structure–activity relationships, aiming to optimize the efficacy of semiochemicals in integrated pest management.
10.1021/jo00139a031
The research explores the synthesis and properties of (E,E)-thiacyclodeca-4,7-diene (1) and its 3-methyl derivative (14) using D-mannitol as the starting material. The purpose of the study was to investigate the stereochemical and conformational behavior of these chiral compounds, which have interesting geometrical properties making them good candidates for such studies. The synthesis involved a series of stereospecific reactions, including the use of enantiomerically pure D-mannitol, (R,R)-cis-2,6-dioxabicyclo[3.3.0]octane (2), (R,R)-1,6-dibromohexane-3,4-diol (3), and various reagents like sodium sulfide, vinylmagnesium bromide, and t-BuOK. The key conclusion was that the synthesized compounds undergo rapid enantiomerization, with an energy barrier of approximately 11 kcal/mol, making them optically inactive. The study also revealed that the flipping motion of the sulfur atom has an energy barrier of around 6 kcal/mol. These findings highlight the dynamic behavior of these compounds and provide insights into their conformational motions.
Xi
