Synthesis and antifungal properties of papulacandin derivatives

• Marjolein van der Kaaden,
• Eefjan Breukink and
• Roland J. Pieters

Beilstein J. Org. Chem. 2012, 8, 732–737, doi:10.3762/bjoc.8.82

• stereochemistry of the double bonds. Moderate biological activity was observed for the derivatives with a side chain based on palmitic acid and linoleic acid. Keywords: antifungal agents; carbohydrate; papulacandins; spiroketal; Introduction In recent years, a steady increase in the incidence of opportunistic

• resistance [1]. Clearly, there is a need for new antifungal therapeutics. The papulacandins are a series of naturally occurring antifungal agents whose isolation and characterization were initially reported by Traxler and co-workers in 1977 (Figure 1) [3][4]. They contain a benzannulated spiroketal unit

• , which has been the signature of a wide series of bioactive natural products [5] and has inspired ample synthetic activity [5][6][7][8]. The papulacandins A–E were isolated from the fermentation broths of Papularia sphaerosperma [3]. They block the synthesis of β-(1,3)-D-glucan by inhibition of β-(1,3)-D