10.1021/ol0708020
The research presents a stereoselective method for synthesizing 4,5-disubstituted imidazolidinones-2-ones from R-amino acids, utilizing a zinc-mediated homologation process involving the Blaise reaction and subsequent reduction. The key reactants include R-amino acids, bromoacetate, and various reducing agents such as sodium cyanoborohydride and sodium in liquid ammonia. The experiments involved the preparation of N-protected R-aminonitriles, their reaction with tert-butyl bromoacetate in the presence of zinc to form enaminoesters, and then reduction to obtain imidazolidinones. The analyses used to determine the success and stereochemistry of the reactions included HPLC, X-ray crystallography, and NMR spectroscopy. The study achieved complete stereoselectivity in the reduction step and provided a route to valuable 1,2-diamine building blocks, which are significant in organic synthesis and biological applications.
10.1016/j.bmcl.2008.04.050
The study presents the rational design and synthesis of novel piperazinone and imidazolidinone inhibitors targeting BACE1, an enzyme implicated in Alzheimer's disease (AD) due to its role in producing β-amyloid peptides, which are toxic to neurons. The researchers aimed to develop potent inhibitors that could potentially slow or halt the progression of AD. The key chemicals used in the study include piperazinones and imidazolidinones, which were designed to interact with both the flap and the S20 pocket of BACE1. These cyclic amine motifs were specifically crafted to achieve both occupancy of the S2 subsite and formation of an additional hydrogen bond to the flap, enhancing the inhibitors' potency. The study involved extensive structure-activity relationship (SAR) analysis around these compounds to optimize their binding affinity and selectivity. The purpose of these chemicals was to serve as therapeutic agents that could reduce BACE1 activity, thereby decreasing AD-like pathology in transgenic mouse models.
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.
10.1021/ol049827e
The study presents a copper sulfate-pentahydrate (CuSO?·5H?O) and 1,10-phenanthroline catalyzed cross-coupling protocol for synthesizing ynamides from alkynyl bromides and amides. This method is more environmentally friendly than using CuCN or copper halides and allows for the synthesis of various ynamides, including sulfonyl and heteroaromatic amine substituted ones. The researchers optimized the protocol by screening different Cu(I) and Cu(II) salts, ligands, solvents, concentrations, bases, and temperatures. They found that CuSO?·5H?O with 1,10-phenanthroline as the ligand provided the best results, yielding ynamides in good isolated yields and suppressing homocouplings. The protocol was successfully applied to a range of substrates, including previously poor ones like azacamphor, imidazolidinone, and acyclic urethanes, as well as lactams. It was also effective in preparing sulfonyl ynamides and vinylogous ynamides with various heteroaromatic amines, demonstrating its versatility and potential impact on organic synthesis.
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