RESUMO
We describe the synthesis of two conjugated macrocycles that are formed from the end-to-end linking of stilbenes. We have named these macrocycles cyclostilbenes. The two cyclostilbene isomers created in this study differ in the configuration of the double bond in their subunits. These macrocycles are formed selectively through a stepwise reductive elimination from a tetraplatinum precursor and subsequent photoisomerization. Single-crystal X-ray diffraction reveals the formation of channel architectures in the solid state that can be filled with guest molecules. The cyclostilbene macrocycles emit blue light with fluorescence quantum yields that are high (>50%) and have photoluminescence lifetimes of â¼0.8-1.5 ns. The breadth and large Stokes shift in fluorescence emission, along with broad excited-state absorption, result from strong electronic-vibronic coupling in the strained structures of the cyclostilbenes.
RESUMO
We have examined peptide-based catalysts for the site-selective thiocarbonylation of a protected form of vancomycin. Several catalysts were identified that either enhanced or altered the inherent selectivity profile exhibited by the substrate. Two catalysts, one identified through screening and another through rational design, were demonstrated to be effective on 0.50-g scale. Deoxygenations led ultimately to two new deoxy-vancomycin derivatives, and surprising conformational consequences of deoxygenation were revealed for one of the new compounds. These effects were mirrored in the biological activities of the new analogues and support a structural role for certain hydroxyls in the native structure.
Assuntos
Antibacterianos/química , Vancomicina/química , Antibacterianos/farmacologia , Cristalografia por Raios X , Enterococcaceae/efeitos dos fármacos , Humanos , Isomerismo , Modelos Moleculares , Conformação Molecular , Oxigênio/química , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Compostos de Sulfidrila/química , Vancomicina/farmacologiaRESUMO
We report a fundamentally unique approach to the catalytic kinetic resolution of amine derivatives based on formamide and thioformamide substrates. Readily accessible histidine-containing peptides mediate the kinetic resolutions with as little as 5 mol % catalyst. Selectivity factors (k(rel)) as high as 43.7 were observed under simple reaction conditions utilizing Boc(2)O as the reagent at room temperature. Mechanistic experiments were conducted that established a higher level of reactivity for thioformamide substrates than for their formamide analogues. The products of these asymmetric reactions were shown to be readily converted to desirable building blocks such as N-Boc-amines and the parent chiral formamide compounds.