Total synthesis and antifungal evaluation of cyclic aminohexapeptides

The need for new therapies to treat systemic fungal infections continues to rise. Naturally occurring hexapeptide echi-nocandin B (1) has shown potent antifungal activity via its inhibition of the synthesis of beta-1,3 glucan , a key fungal cell wall component. Although this series of agents has been limited thus far based on their physicochemical characteristics, we have f ound that the synthesis of analogues bearing an aminoproline residue in the 'northwest' position imparts greatly improved water solubility ( > 5 mg/mL ). The synthesis and structure-activity relationships (SAR) based on whole cell and upon in vivo activity of the series of compounds are reported. (C) 2000 Elsevier Science Ltd. All rights reserved.