RESUMO
To date the prototype Nazarov cyclization of a cross-conjugated pentadienone to the core structure of the rocaglate natural products has not been successful (9 into 12). It has been found that this conversion can be achieved by the use of acetylbromide in excellent yield and results in a strategically very direct route to these antitumor agents.
Assuntos
Acetatos/química , Benzofuranos/química , Antineoplásicos/farmacologia , Química Farmacêutica/métodos , Reagentes de Ligações Cruzadas/química , Ciclização , Modelos Químicos , Estrutura Molecular , Oxigênio/química , Extratos Vegetais/metabolismo , EstereoisomerismoRESUMO
The predictable relationship between beta-amino acid sequence and folding has inspired several biological applications of beta-peptides. For many such applications, it would be desirable to prepare and screen beta-peptide libraries. However, standard peptide synthesis protocols are not efficient enough to support a library approach for many types of beta-peptides. We recently optimized the solid-phase synthesis of beta-peptides using microwave irradiation, and we have now adapted this approach to synthesis on polystyrene macrobeads. We rapidly prepared a high-quality beta-peptide combinatorial library via a split-and-mix strategy. This library was screened in search of beta-peptide antagonists of the p53-MDM2 protein-protein interaction.
