Asymmetric Synthesis of (−)-Catunaregin, an Angiogenesis Inhibitor from Mangroves

We describe here an enantioselective synthesis of (-)-catunaregin (1), a bioactive agent from Mangrove plants. Our synthesis features an Evans' asymmetric syn-aldol reaction, cross-metathesis to an enone, substrate controlled 1,4-addition, a one-pot cyclization to construct the O-bridged tetrahydrofuropyran core, and deprotection to furnish (-)-catunaregin (1). Our synthetic investigations into the synthesis of (-)-epicatunaregin (2) from a common intermediate resulted in an interesting structural variant, which was fully characterized by X-ray diffraction analysis. The present synthesis provides convenient access to enantiomeric catunaregin natural products and their structural variants.