Total synthesis of biologically active natural products possessing unique structural features

This review describes the total synthesis of natural products involving kopsine, popolophuanone E, hydantocidin, and huperzine A, all of which possess not only unique structural features but also prominent biologically properties. The first total synthesis of the heptacyclic indole alkaloid kopsine was accomplished by employing intramolecular Diels-Alder reactions and Pummerer-type cyclization as the key steps. In the synthetic studies of popolophuanone E, a topoisomerase-II inhibitor from a marine sponge, popolophuanone E trimethyl ether was successfully synthesized by a method featuring the biogenetic-type annulation. The synthetic pathway to hydantocidin, a novel herbicide from Streptomyces sp., has been developed based on the plausible biosynthetic pathway. Total syntheses of both enantiomers of huperzine A. a powerful selective inhibitor of acetylcholinesterase, were accomplished by employing two types of methods which involves the tandem Cinchona alkaloids-promoted asymmetric Michael addition/aldol reaction and the palladium-catalyzed asymmetric bicycloannulation. Furthermore, the novel fluorinated huperzine A analogues were synthesized in order to explore the structure-activity relationships.