RESUMO
Trichloroacetimidates are useful reagents for the synthesis of esters under mild conditions that do not require an exogenous promoter. These conditions avoid the undesired decomposition of substrates with sensitive functional groups that are often observed with the use of strong Lewis or Brønsted acids. With heating, these reactions have been extended to benzyl esters without electron-donating groups. These inexpensive and convenient methods should find application in the formation of esters in complex substrates.
Assuntos
Acetamidas/química , Cloroacetatos/química , Elétrons , Ésteres/química , Ácidos Carboxílicos/químicaRESUMO
An intermolecular alkylation of sulfonamides with trichloroacetimidates is reported. This transformation does not require an exogenous acid, base, or transition metal catalyst; instead the addition occurs in refluxing toluene without additives. The sulfonamide alkylation partner appears to be only limited by sterics, with unsubstituted sulfonamides providing better yields than more encumbered N-alkyl sulfonamides. The trichloroacetimidate alkylating agent must be a stable cation precursor for the substitution reaction to proceed under these conditions.
Assuntos
Acetamidas/química , Cloroacetatos/química , Sulfonamidas/química , Alquilação , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Cromatografia Líquida de Alta Pressão , Espectroscopia de Prótons por Ressonância Magnética , TemperaturaRESUMO
Recently, inhibition of the SH2-containing inositol 5'-phosphatase 1 (SHIP1) has become an attractive strategy for facilitating engraftment of MHC-I mismatched bone marrow grafts, increasing the number of adult stem cells in vivo, and inducing mobilization of hematopoietic stem cells. Utilizing high-throughput screening, two quinoline small molecules (NSC13480 and NSC305787) that inhibit SHIP1 enzymatic activity were discovered. New syntheses of these inhibitors have been developed which verified the relative stereochemistry of these structures. Utilizing this synthetic route, some analogs of these quinolines have been prepared and tested for their ability to inhibit SHIP. These structure activity studies determined that an amine tethered to the quinoline core is required for SHIP inhibition. SHIP inhibition may explain the antitumor effects of similar quinoline amino alcohols and provides an impetus for further synthetic studies in this class of compounds.
Assuntos
Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Inositol Polifosfato 5-Fosfatases/antagonistas & inibidores , Quinolinas/química , Quinolinas/farmacologia , Domínios de Homologia de src , Adamantano/análogos & derivados , Ativação Enzimática/efeitos dos fármacos , Estrutura MolecularRESUMO
Trichloroacetimidates are useful alkylating agents for aromatic amines, requiring only a catalytic amount of a Brønsted acid to facilitate the reaction. Monoalkylation predominates under these conditions. Electron-poor anilines provide superior yields, with electron-rich anilines sometimes showing competitive Friedel-Crafts alkylation. A single flask protocol with formation of the imidate in situ is demonstrated, providing a convenient method for the direct substitution of alcohols with anilines. Reaction with a chiral imidate favors a mechanism that proceeds through a carbocation intermediate.