Novel spirodihydrobenzofuranlactams as antagonists of endothelin and as inhibitors of HIV-1 protease produced by Stachybotrys sp .1. Fermentation, isolation and biological activity

Six novel spirodihydrobenzofuranlactams I similar to VI(1 similar to 6) and a related spirodihydrobenzofuranalcohol, the previously described natural compound L-611,776 (7), were isolated from cultures of two different Stachybotrys species. These secondary metabolites showed antagonistic effects in the endothelin receptor binding assay and inhibited HIV-I protease. Both biological activities are novel for L-671,776 (7). The pseudosymmetric spirodihydrobenzofuranlactam VI (6) is the most potent representative of this class of compounds exhibiting IC50 values of 1.5 mu M in the ET-A receptor binding assay and 11 mu M in the HIV-1 protease inhibition assay.