NOVEL DRIMANE SESQUITERPENE ESTERS FROM ASPERGILLUS-USTUS VAR PSEUDODEFLECTUS WITH ENDOTHELIN RECEPTOR-BINDING ACTIVITY

A series of novel drimane sesquiterpene esters (1 similar to 6) was is olated from fermentations of Aspergillus ustus var. pseudodeflectus an d their structures elucidated by spectroscopic methods including the H MQC, HMBC and INADEQUATE NMR experiments. The major component of the f ermentation, 1, was y-2',4',6'-trien)-9-hydroxydrim-7-ene-11,12-olide. Compounds 1, 2, 3 and 5 exhibited endothelin receptor binding inhibit ory activity against rabbit endothelin-A and rat endothelin-B receptor s with IC50 values in the range 20 similar to 150 mu M. These compound s had similar levels of activity in assays for binding to human endoth elin A and endothelin B receptors. The isolation of 9,11-dihydroxy-6-o xodrim-7-ene, 7, a probable biosynthetic precursor to the drimane este rs is also reported.