Compounds 4-7, analogs of the potent protein kinase C (PKC) inhibitor balanol (-)-1, were synthesized and their potency against PKC was compared with racemic balanol and other related analogs. These cyclopentane-based analogs were found to be, in general, more potent PKC inhibitors than balanol. Activation of the protein kinase C (PKC) family of enzymes leads to modulation of a number of cellular processes 1 and is thought to underlie several disease states. 2 Thus, compounds that inhibit PKC may prove useful as chemotherapeutic agents for human diseases. Balanol (-)-1 is a potent PKC inhibitor recently isolated in our laboratories from the fungus Verticillium balanoides. 3 As a result of further studies intended to determine the structure-activity relationships of balanol analogs we identified compounds 2 and 3, two equally potent balanol analogs in which the balanol perhydroazepine is replaced with a pyrrolidine and cyclopentane ring, respectively. 4 This aroused an interest in evaluating more analogs having a similar five-membered ring substructure in which the pyrrolidine heteroatom is moved to an exocyclic position. Such compounds can be viewed as analogs of 3 and were expected to reveal the influence, if any, of the substitution pattern around the five-membered ring on the potency of these molecules against PKC. We describe herein the syntheses, shown in Scheme 1-4, and the biological activities of seven such analogs, namely 4-7. 5