RESUMO
A four-component reaction for the synthesis of heterocyclic boronates is reported. Readily available hydrazides, α-hydroxy aldehydes, and two orthogonally reactive boronic acids are combined in a single step to give structurally distinct bicyclic boronates, termed dioxadiazaborocines (DODA borocines). In this remarkable process, one boronic acid reacts as a carbon nucleophile and the other as a boron electrophile to provide enantio- and diastereomerically pure heterocyclic boronates with multiple stereocenters in high yields.
Assuntos
Ácidos Borônicos/síntese química , Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Aldeídos/síntese química , Aldeídos/química , Ácidos Borônicos/química , Compostos Bicíclicos Heterocíclicos com Pontes/química , Técnicas de Química Combinatória , CiclizaçãoRESUMO
An enantioselective total synthesis of trioxacarcin DC-45-A2 (1) featuring a novel Lewis acid-induced cascade rearrangement of epoxyketone 6 to forge the polyoxygenated 2,7-dioxabicyclo[2.2.1]heptane core of the molecule is described.
Assuntos
Aminoglicosídeos/síntese química , Antibióticos Antineoplásicos/síntese química , Ácidos de Lewis/química , Aminoglicosídeos/química , Estrutura Molecular , EstereoisomerismoRESUMO
A series of 5-substituted 2-pyrrolidinones was synthesized through a one-pot ruthenium alkylidene-catalyzed tandem RCM/isomerization/nucleophilic addition sequence. The intermediates resulting from RCM/isomerization showed reactivity toward electrophiles in aldol condensation reactions which provided a new entry for the total synthesis of the antileukemic natural product violacein.
Assuntos
Indóis/síntese química , Rutênio/química , Alcenos/química , Catálise , Técnicas de Química Combinatória , Ciclização , Indóis/química , Estrutura Molecular , EstereoisomerismoRESUMO
Apoptotic induction mechanisms are of crucial importance for the general homeostasis of multicellular organisms. In cancer the apoptotic pathways are downregulated, which, at least partly, is due to an abundance of inhibitors of apoptosis proteins (IAPs) that block the apoptotic cascade by deactivating proteolytic caspases. The Smac protein has an antagonistic effect on IAPs, thus providing structural clues for the synthesis of new pro-apoptotic compounds. Herein, we report a solid-phase approach for the synthesis of Smac-derived tetrapeptide libraries. On the basis of a common (N-Me)AVPF sequence, peptides incorporating triazoloprolines and biarylalanines were synthesized by means of Cu(I)-catalyzed azide-alkyne cycloaddition and Pd-catalyzed Suzuki cross-coupling reactions. Solid-phase procedures were optimized to high efficiency, thus accessing all products in excellent crude purities and yields (both typically above 90%). The peptides were subjected to biological evaluation in a live/dead cellular assay which revealed that structural decorations on the AVPF sequence indeed are highly important for cytotoxicity toward HeLa cells.
