Refernces
10.1021/jm070864w
The research focuses on the development of dual inhibitors targeting Inosine Monophosphate Dehydrogenase (IMPDH) and Histone Deacetylases (HDACs) for cancer treatment, specifically for Chronic Myelogenous Leukemia (CML). The study involves the synthesis and evaluation of mycophenolic hydroxamic acid (MAHA) and a SAHA analogue, which are found to inhibit both IMPDH and HDACs, with potential as antiproliferation and differentiation-inducing agents. Experiments include enzyme assays to determine IMPDH and HDAC inhibition, proliferation assays using human myelogenous leukemia K562 cells, and differentiation assays to evaluate the compounds' effects on cellular differentiation. Reactants used in the chemical synthesis of these inhibitors include mycophenolic acid, various protected hydroxylamines, and other organic compounds, while analyses involve high-performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR), and high-resolution mass spectrometry (HRMS) to characterize the synthesized compounds.
10.1016/S0040-4039(01)01862-7
The study focuses on the chemoselective reduction of the imino (C≡N) bond in a series of oximino ethers using zirconium tetrachloride-sodium borohydride reagent, aiming to synthesize O,N-disubstituted hydroxylamines without cleaving the N-O bond. The researchers observed that precomplexation with zirconium cation in ether-methylene chloride solutions was effective for selective C≡N bond reduction, and the stereochemical control was dictated by Lewis acid coordination complexes of E- and Z-oximino ethers, leading to the preferred diastereofacial delivery of external hydride. Key chemicals used in the study include zirconium tetrachloride (ZrCl4), sodium borohydride (NaBH4), diethyl ether (Et2O), and methylene chloride (CH2Cl2), which served to facilitate the reduction reaction and control the stereochemistry of the products. The study also involved the use of various oximino ethers as substrates for the reduction, and the products were characterized by their yields and diastereomeric ratios, indicating the selectivity and stereochemical control achieved in the reactions.
10.1016/j.farmac.2004.08.003
The study focuses on the synthesis and preliminary pharmacological evaluation of a new series of muscarinic antagonists derived from 2,2-diphenyl-2-ethylthio-acetic acid esters. These compounds were designed to probe the binding site cavity of muscarinic receptors, which are found in the central and peripheral nervous system and play a crucial role in various vital functions. The researchers aimed to enhance the potency and selectivity of these antagonists by decorating the parent molecules with linkers of different lengths, carrying an amino group to potentially interact with an anionic function outside the recognition site of the receptor. The chemicals used in the study included 2,2-diphenyl-2-ethylthio-acetic acid esters, various chloramines, amino alcohols, and other organic compounds to synthesize the new series of compounds (3–20). The purpose of these chemicals was to create probes that could interact with the muscarinic receptor subtypes and potentially lead to the development of more selective and potent therapeutic agents for pathologies such as smooth muscle hyperactivity and neurodegenerative diseases. However, the study found that while the new compounds showed some increase in affinity, they lacked subtype selectivity and did not meet the expected outcomes, leading to the identification of a series of compounds with a peculiar pharmacological profile.
10.1021/ja800053t
The research aims to develop a practical method for the synthesis of enantioenriched peptide-derived R-ketoacids, which are crucial for chemoselective ligation reactions that allow the coupling of unprotected molecular fragments via selective bond forming reactions. The study addresses the challenge of synthesizing these R-ketoacids without epimerization, in a manner compatible with unprotected peptide side chains and iterative peptide synthesis methods. The researchers initially explored cyanophosphorus ylides for this purpose but encountered difficulties with epimerization and harsh oxidation conditions. They then turned to sulfur ylides, which proved to be more effective under mild, aqueous conditions. The key chemicals used include sulfur ylides, Oxone for oxidation, and hydroxylamines for the ligation reaction. The study concludes that using sulfur ylides in combination with Oxone provides a robust and chemoselective method for synthesizing C-terminal peptide R-ketoacids with minimal epimerization. The method is compatible with various amino acid side chains and can be integrated with standard peptide synthesis protocols. Future work will focus on translating this method to solid-phase peptide synthesis to enable the preparation of longer peptide R-ketoacids for decarboxylative peptide ligation reactions.
10.1016/j.tetlet.2003.11.133
The study presents a concise synthesis method for a novel class of homochiral aromatic amino acid surrogates, featuring tetrahydroindazole or benzisoxazole systems. These surrogates were synthesized through the acylation of cyclic 1,3-diketone by the side-chain carboxyl functionality of specific amino acid precursors, followed by a regioselective condensation with hydrazine, N-benzylhydrazine, and hydroxylamine. The synthetic strategy is versatile, allowing for the creation of structurally diverse derivatives. These novel amino acids can be efficiently incorporated into proteins and have potential applications in imparting unique properties to biological peptides. The study also includes the synthesis of Na-Fmoc-protected derivatives, which are useful for solid-phase peptide assembly, and the exploration of the stereochemistry integrity of the homochiral starting material through chemical transformations. The synthesized amino acids offer opportunities as structural surrogates of tryptophan and as building blocks for designing molecular probes.
