Estudos visando a síntese total da combretastatina D-2

A Combretastatina D-2 é uma macrolactona isolada em 1989 da árvore sul africana Combretum caffrum. A partir de 77 Kg da casca foram obtidos 5,8 mg do produto natural - um rendimento de 7,5 × 10-6 %. Este composto exibiu atividade antineoplásica sobre células leucêmicas P-388 ao impedir a desmontagem dos microtúbulos durante a mitose celular. O mecanismo de ação incomum tornou a Combretastatina D-2 um alvo de permanente investigação na farmacologia anticâncer. Assim, com o desejo de contribuir com as investigações sobre esta macrolactona, neste trabalho é proposta a investigação de uma nova estratégia de síntese para a preparação deste produto natural. A estratégia sintética proposta foi baseada no acoplamento de dois fragmentos principais: A e B. O fragmento A consistiu em um composto de boro, sintetizado na forma de um ácido borônico ou um trifluoroborato de potássio em rendimentos globais moderados. Para a preparação do fragmento B, um fenol, foram envolvidas reações de acoplamento do tipo Sonogashira e reação de hidrogenação catalític

Three tetrahydro-1,4-epoxy-1-benzazepines carrying pendent heterocyclic substituents: supramolecular structures in zero, one or two dimensions

(2SR,4RS)-7-Fluoro-2-exo-(2-furyl)-2,3,4,5-tetrahydro-1H-1,4- epoxy-1-benzazepine, C14H12FNO2, (I), crystallizes with Z' = 2 in the space group P2(1)/c. A combination of three C-H center dot center dot center dot O hydrogen bonds and one C-H center dot center dot center dot N hydrogen bond links the molecules into a complex chain of rings, and pairs of such chains are linked into a tube-like structure by two C-H center dot center dot center dot pi(arene) hydrogen bonds. There are no hydrogen bonds in the structure of racemic (2SR,4RS)-2-exo-(5-bromo-2-thienyl)- 7-fluoro-2,3,4,5-tetrahydro-1H-1,4-epoxy-1-benzazepine, C14H11BrFNOS, (II), while the molecules of (2S,4R)-2-exo- (5-bromo-2-thienyl)-7-trifluoromethoxy-2,3,4,5-tetrahydro-1H- 1,4-epoxy-1-benzazepine, C15H14BrF3NO2S, (III), are linked into sheets by a combination of two C-H center dot center dot center dot O hydrogen bonds and one C-H center dot center dot center dot pi(arene) hydrogen bond. The significance of this study lies in its observation of the wide variation in the patterns of supramolecular aggregation, consequent upon modest changes in the peripheral substituents.</p

Three aryl-substituted tetrahydro-1,4-epoxy-1-benzazepines: hydrogen-bonded structures in two or three dimensions

In (2SR,4RS)-7-chloro-2-exo-(4-chlorophenyl)-2,3,4,5-tetrahydro-1H-1,4-epoxy-1-benzazepine, C16H13Cl2NO, (I), the molecules are linked by a combination of C-H center dot center dot center dot O and C-H center dot center dot center dot N hydrogen bonds into a chain of edge-fused R-3(3)(12) rings. The isomeric compound (2S,4R)-7-chloro-2-exo(2-chlorophenyl)-2,3,4,5-tetrahydro-1H-1,4-epoxy-1-benzazepine, (II), crystallizes as a single 2S, 4R enantiomer and the molecules are linked into a three-dimensional framework structure by two C-H center dot center dot center dot O hydrogen bonds and one C-H center dot center dot center dot( arene) hydrogen bond. The molecules of (2S,4R)-7chloro-2-exo-(1-naphthyl)-2,3,4,5-tetrahydro-1H-1,4-epoxy-1benzazepine, C20H16ClNO, (III), are also linked into a three-dimensional framework structure, here by one C-H center dot center dot center dot O hydrogen bond and two C-H center dot center dot center dot pi(arene) hydrogen bonds. The significance of this study lies in its observation of the variations in molecular configuration and conformation, and in the variation in the patterns of supramolecular aggregation, consequent upon modest changes in the peripheral substituents.</p