Synthesis of Cytotoxic Marine Macrolides: An Aldol-Based Approach to Spongistatin 1 (Altohyrtin A)

Marine organisms provide an important source of natural product diversity with an associated range of significant biological activities, which may provide new leads for drug discovery. For example, some of the most primitive multicellular invertebrates are sponges, which may be associated with cytotoxic metabolites having potential for development as anti-cancer drugs (e.g., the halichondrins and discodermolide). In this regard, the spongistatins 1,2 (altohyrtins3) are a novel group of potent cytotoxic macrolides,4 which have recently attracted considerable interest and excitement from marine natural product and synthetic organic chemists.