Madangamine alkaloids isolation

This chapter is focused on madangamines, a small group of complex diamine alkaloids Isolated from marine sponges of the order Haplosclerlda, and covers their Isolation, characterization, biogenesis, biological activity, and synthesis. Structurally, madangamines are pentacyclic alkaloids with an unprecedented skeletal type. 

The synthesis of the tricyclic core of the cytotoxic marine alkaloid Madangamine required an efficient method to generate the central quaternary carbon function. Weinreb employed an aza-Claisen rearrangement in the presence of a palladium catalyst [21c]. After treatment of ketone 116 subsequently with TOSMIC and DIBALH, the formed carbaldehyde 117 was reacted with diallylamine in the presence of Pd(OCOCFj)2/PPh,. Initially, the enamine 118 was formed, which underwent diastereoselective aza-Claisen rearrangement The unsaturated imine 119 was cleaved with aqueous HCl and the corresponding aldehyde 120 was isolated in 68% yield. Several further steps allowed one to complete the synthesis of the core fragment 121 of the natural product (Scheme 10.27). 

Ptire madangamines A—C and F were isolated as optically active compounds (see Table 1 for the [a] values). Although the absolute configuration of the alkaloids has not been unambiguously established, it may be tentatively deduced by correlation with the putative precursor ingenamines (see Section 3). No X-ray crystallographic analysis of these alkaloids is available to date. 

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