Structure Elucidation of Lolitrem F, a Naturally Occurring Stereoisomer of the Tremorgenic Mycotoxin Lolitrem B, Isolated from Lolium perenne Infected with Acremonium lolii

A new lolitrem, lolitrem F (2), was isolated from endophyte-infected perennial ryegrass. Its structure was shown by mass spectrometry and one- and two-dimensional NMR spectroscopy to be a 31,35-cis-fused isomer of lolitrem B. Base-catalyzed epimerization of 2 and lolitrem B (1) afforded their 31-epimers (4 and 3, respectively). Comparison with spectral data for 1 and 31-epi-lolitrem B (3) established lolitrem F to be 35-epi-lolitrem B. Compounds 1, 2, and 4 were equally tremorgenic in a mouse bioassay, but 3 was nontremorgenic. Base-catalyzed exchange of H-31 was found to permit efficient incorporation of deuterium (and potentially, therefore, of tritium) into 1 and 3. Keywords: Acremonium lolii; Lolium perenne; endophyte; lolitrem; tremor; ryegrass staggers; neurotoxin; mycotoxin