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.