Diaryl ether and diaryl thioether syntheses on solid supports via copper (I)-mediated coupling.
An efficient method to synthesize diaryl ethers and thioethers on solid supports is described. Starting from immobilized phenols or arylhalides, coupling with an access of aryliodides/arylbromides or phenolic/thiophenolic substrates in solution was successful in the presence of CuCl and Cs(2)CO(3) as base. Coupling conditions known from solution-phase syntheses of diaryl ethers have been effectively modified and adapted to solid-phase synthesis. Optimized conditions enabled the coupling of sterically hindered and/or electronically deactivated aryl moieties. After coupling, a newly developed diversity-generating linker based on cinnamic acid allowed the diaryl ethers to be cleaved from the resin either via saponification/transesterification or via ozonolysis. Latter offers the possibility of generating several additional compounds by simple variation of the cleavage conditions. The target substances were generally isolated in good to excellent yields and high purities.
Solid Phase Chemistry for the Directed Synthesis of Biologically Active Polyamine Analogs, Derivatives, and Conjugates
Polyamines in naturally occurring compounds are biologically active molecules that do not display a great diversity but are very abundant in almost all organisms. Their functions comprise antibiotics, immunosuppressants, toxins, and many others. In most biologically active compounds the polyamine chain is coupled to other functionalities making the polyamine an excellent template for solid phase chemistry and combinatorial approaches. This review comprises common techniques for the synthesis of polyamines and polyamine derivatives on solid support. It includes the description of basic synthesis requirements such as of suitable resins, new linkers, reaction conditions for generation of biologically active polyamines and polyamines in natural products as well as the description of protection groups. Moreover, it will focus on the modular coupling of the amine building blocks using different synthesis strategies. Thus, the advantages of performing reactions on polymer-supported substrates in terms of avoiding side reactions and facilitating product/metal separation are highlighted.
The harpin ribozyme: the roles of ions in RNA cleavage.
The cleavage reaction of the hairpin ribozyme is facilitated by divalent metal ions, such as Mg2+, or by non-metallic polycations, such as the polyamine spermine. We show substantial enhancement of cleavage with combinations of metallic and non-metallic ions. In addition we elucidate the locations of some ion binding sites by Fenton chemistry.