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

A new lolitrem, lolitrem F (<b>2</b>), 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-<i>cis</i>-fused isomer of lolitrem B. Base-catalyzed epimerization of <b>2</b> and lolitrem B (<b>1</b>) afforded their 31-epimers (<b>4</b> and <b>3</b>, respectively). Comparison with spectral data for <b>1</b> and 31-<i>epi</i>-lolitrem B (<b>3</b>) established lolitrem F to be 35<i>-epi</i>-lolitrem B. Compounds <b>1</b>, <b>2</b>, and <b>4</b> were equally tremorgenic in a mouse bioassay, but <b>3</b> was nontremorgenic. Base-catalyzed exchange of H-31 was found to permit efficient incorporation of deuterium (and potentially, therefore, of tritium) into <b>1</b> and <b>3</b>. Keywords: <i>Acremonium lolii</i>; <i>Lolium perenne</i>; endophyte; lolitrem; tremor; ryegrass staggers; neurotoxin; mycotoxin