Total synthesis of the microbial antitumor antibiotics actinobolin and bactobolin

Actinobolin is found to inhibit growth of both gram-positive and gram-negative bacteria. Additionally, actinobolin has been reported to have weak antineoplastic activity and dental cariostatic activity. It has been found that actinobolin interferes with protein synthesis at a late stage in mammalian cells and this phenomenon may account for the biological activity of the metabolite. Currently, actinobolin is shown to have immunosuppressive activity. The structure and absolute stereochemistry of actinobolin was formulated by application of an elegant combination of chemical degradation and spectroscopic methods. Stereostructure is subsequently fully confirmed by X-ray crystallography. A congener of actinobolin, bactobolin, is isolated from Pseudomonas yoshitomiensis Y-12278. Bactobolin is structurally identical to actinobolin except for the unusual dichloromethyl group at C-3. This metabolite is also found to have significant antibacterial activity. However, bactobolin shows considerably higher potency in antitumor screens than bactobolin. Two closely related bactobolin analogs have been isolated from Pseudomonas and are also found to have good antitumor activity.