Synthesis and structure-activity relationships of novel 3′-Hty-substituted pneumocandins

A series of pneumocandin B0 analogs substituted at the 3′ -position of the homotyrosine (Hty) residue have been prepared and evaluated for their inhibition of 1,3-β-( )-glucan synthesis and for their antifungal activity against C. albicans. Cationic analogs displayed enhanced antifungal properties. The phenolic hydroxyl is involved in a critical hydrogen-bond at the binding site of the enzyme.