Enantioselective Synthesis of the Cyclopentyl Core of the Axinellamines

Abstract

Axinellamines A−D (1−4) are novel bis-guanidine alkaloids isolated from the marine sponge Axinella sp. of which Axinellamines B−D (2−4) have been shown to possess bactericidal activity against Helicobacter pylori, a bacterium implicated in pepticular and gastric cancer.1 These natural products are noteworthy for the structural complexity of the polycyclic framework incorporating fused and spirocyclic ring systems. Moreover, embedded within these structures is a stereochemically complex and densely functionalized cyclopentyl core that presents a daunting synthetic challenge. A similarly substituted cyclopentane core can be found in palau'amine 5 which critically differs from that of 1−4 in the relative stereochemical relationships of the pendant functionality.2 Palau'amine 5 has attracted considerable attention due to its potent antibiotic, immunosuppressive, and cytotoxic properties (Chart 1).