Reactions of β-carotene with cigarette smoke oxidants. Identification of carotenoid oxidation products and evaluation of the prooxidant/antioxidant effect

An experimentally simple and inexpensive catalyst system was developed for the amidation of aryl halides by using 0.2-10 mol % of Cul, 5-20 mol % of a 1,2-diamine ligand, and K3PO4, K2CO3, or Cs2CO3 as base. Catalyst systems based on N, N′-dimethylethylenediamine or trans-N,N′-dimethyl-1,2-cyclohexanediamine were found to be the most active even though several other 1,2-diamine ligands could be used in the easiest cases. Aryl iodides, bromides, and in some cases even aryl chlorides can be efficiently amidated. A variety of functional groups are tolerated in the reaction, including many that are not compatible with Pd-catalyzed amidation or amination methodology

Mechanism-Based Solution to the ProTide Synthesis Problem: Selective Access to Sofosbuvir, Acelarin, and INX-08189

A general and efficient method for the synthesis of pronucleotide (ProTide) 5'-phosphoramidate monoesters is reported. This method consists of a highly stereoselective 5'-phosphorylation mediated by dimethylaluminum chloride to afford the desired target ProTides in excellent yields without employing 3'-protection strategies. The application of this methodology to the synthesis of a number of pharmaceutically relevant compounds currently marketed or under investigation in clinical research is demonstrated.Fil: Simmons, Bryon. Merck & Co.; Estados UnidosFil: Liu, Zhuqing. Merck & Co.; Estados UnidosFil: Klapars, Artis. Merck & Co.; Estados UnidosFil: Bellomo Peraza, Ana Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias ; Argentina. Merck & Co.; Estados UnidosFil: Silverman, Steven M.. Merck & Co.; Estados Unido

Dual Imaging Single Vesicle Surface Protein Profiling and Early Cancer Detection

The first general method for the Pd-catalyzed amination of aryl tosylates and benzenesulfonates was developed utilizing ligand 1, which belongs to a new generation of biaryl monophosphine ligands. In addition, the new catalyst system for the first time enables amidation of aryl arenesulfonates and aqueous amination protocols that do not necessitate the use of cosolvents. The substrate scope has been significantly expanded to include aryl halides containing primary amides and free carboxylic acid groups. In the case of multifunctional substrates, the Pd-catalyzed amination can provide selectivity that is complementary to the Cu-catalyzed C-N bond-forming processes. Copyright © 2003 American Chemical Society

Asymmetric Synthesis of <i>N</i>‑Boc‑(<i>R</i>)‑Silaproline via Rh-Catalyzed Intramolecular Hydrosilylation of Dehydroalanine and Continuous Flow <i>N</i>‑Alkylation

An asymmetric synthesis of a silicon-containing proline surrogate, <i>N</i>-Boc-(<i>R</i>)-silaproline (<b>1</b>), is described. Starting from <i>N</i>-Boc-dehydroalanine ester, deprotonation, followed by <i>N</i>-alkylation with chloromethyldimethylsilane under flow conditions, afforded the <i>N</i>-alkylated product <b>8</b> in 91% yield. An unprecedented enantioselective (NBD)₂RhBF₄/Josiphos 404-1 catalyzed 5<i>-endo-trig</i> hydrosilylation afforded the silaproline ester in 85–90% yield and >95% ee. Subsequent saponification and salt formation upgraded <b>1</b> to >99% ee