Synthesis of macrocyclic lactam/lactone derivatives having antimicrobial activity

Abstract: A number of new synthetic methods have been developed that are applicable to several types of antibiotics possessing macrocyclic lactone or lactam structures. These methods have permitted the synthe-sis of several key subunits of these compounds, and progress has been made on the total synthesis of some of these antibiotics. The type A streptogramin antibiotics have served as a special focus of these efforts. In addition, a combination of microbiological and chemical methods have been investigated for the direct modification of the naturally occurring antibiotics. Included among macrocyclic compounds of current biomedical interest are the streptogramin antibi-otics (l), the trienomycins (2), and the iejimalides (3). These compounds occur naturally as highly func-tionalized macrocyclic lactam or lactone systems. Madumycin I c1> is a representative member of the type A streptogramin series which comprises several antibiotics having wide-ranging applications. The trieno-mycins (2) and the iejimalides a show potent cytotoxicity in a variety of assays. The rich structural diversity of these compounds and their important biological activity has prompted us to use them as platforms for the development of new synthetic methods that may ultimately be applied to the total synthesis of these compounds and various analogues for further biomedical investigations. Con-siderable progress has been made in these efforts. In this brief paper, our results will be exemplified b