The Rickiols: 20‐, 22‐, and 24‐membered Macrolides from the Ascomycete Hypoxylon rickii

In preceding studies the neotropical ascomycete Hypoxylon rickii turned out to be a prolific source of new secondary metabolites, considering that we had obtained terpenoids with five different scaffolds along with a series of terphenyls. From the mycelial extracts of a 70 L scale fermentation of this strain we additionally isolated nine new macrolides ( 1 – 9 ) by RP‐HPLC. The planar structures were elucidated by NMR spectroscopy complemented by HR‐ESIMS. The relative configurations were assigned by J ‐based configuration analyses and confirmed by Kishi′s Universal Database. Subsequently, the absolute configurations were assigned by Mosher′s method using the shift analysis of a tetra‐MTPA derivative. For rickiol A ( 1 ) and E ( 5 ) we observed transesterification of 20‐membered ring structures to 22‐membered isomers rickiol A2 ( 6 ) and E2 ( 7 ), and to 24‐membered isomers rickiol A3 ( 8 ) and rickiol E3 ( 9 ), respectively. Cytotoxic effects and moderate antibiotic activity against Gram‐positive bacteria were observed for 1 – 8 and 1 – 6 and 8 , respectively. The total synthesis of rickiol E3 ( 9 ) established easier access to these compounds.