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

Abstract

Six novel spirodihydrobenzofuranlactams I ~ VI (1 ~ 6) and a related spirodihydrobenzofuranalcohol, the previously described natural compound L-671,776 (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-1 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 μM in the ET-A receptor binding assay and 11 μM in the HIV-1 protease inhibition assay.