Prenylated indole alkaloids containing the bicyclo-[2.2.2]diazaoctane ring system as a core structure, now number more than 38 family members. These natural substances, produced by various genera of fungi, in particular Aspergillus and Penicillium spp. (among others), exhibit a range of interesting structural and stereochemical features. Significantly, a myriad of biological activities, including insecticidal, antitumor, anthelmintic, calmodulin inhibitory, and antibacterial properties, are displayed by members of this family. Structurally, these substances arise from the oxidative condensation of one or two isoprene units, tryptophan, and another cyclic amino acid residue such as proline, b-methylproline, or pipecolic acid. With respect to the relative stereochemistry within the core bicyclo[2.2.2]diazaoctane ring system, all of the known members of the paraherquamide family, for example, paraherquamides (1 and 2), stephacidins (3 and 4), and notoamides (5 and 6) possess a syn configuration, while only the brevianamides (9 and 10) possess the anti relative configuration (Scheme 1). The syn/anti relation-ship refers to the relative configuration between the C19ÀC22 bond (sclerotiamide numbering) and the C17ÀN13 bond of the cyclic amino acid residue (proline, b-methylproline, or pipecolic acid; Scheme 2). This relationship reveals that to construct the core ring system biosynthetically in the oxidative cyclization process(es) both faces of the isoprene-derived dienophile participate in the ring-forming process. However, Scheme 1. Structures of several members of the paraherquamide/ stephacidin/brevianamide family of prenylated indole alkaloids.