In our screening program for cholecystokinin (CCK) binding inhibitors of CCK type B (CCKB) receptors from microbial origin, we isolated a novel CCKB receptors antagonist, Ro 09-1468 from the culture broth of Streptomyces sp. NR0489. The molecular formula of Ro 09-1468 was determined to be C_<31> H_<38>O_8S, on the basis of HRFAB-MS, ^1H and ^<13>C NMR spectral data. The structure of Ro 09-1468 was determined to be 1 (Fig. 1), a macrocyclic compound with α-acyltetronic acid and tetrahydro-thiophene moieties, based on two-dimensional NMR techniques. Ro 09-1468 specifically inhibited CCK8 (the carboxy terminal octapeptide of CCK) binding to receptors (CCKB) in rat cerebral cortex membranes with an IC_<50> of 3.2nM.
