Design and preparation of cyclopeptamine antifungal agents

The lack of agents for infections caused by pathogenic fungi has demanded further investigation of a key lead structure which has shown promise, echinocandin B. In recent years, two analogs of this cyclic hexapeptide are proceeding through the clinic exhibiting proof of concept for the target of these drugs. This target, the ss-1,3-glucan synthesis complex, produces the majority of fungal cell wall glucan in many of the most pathogenic fungi such as Candida. A methodical structure-activity relationship review of several major fragments of these highly functionalized molecules is described. This information is useful for determination of the minimum functional/structural requirements for design of an optimal compound in this series. Analogs are presented with their accompanying whole cell antifungal activities.