Novel macrocyclic and polycyclic norcembranoid diterpenes from Sinularia species of soft coral: Structural relationships and biosynthetic speculations

Polycyclic norcembranoid diterpenes are a rare group of natural products which are found exclusively in soft corals of the genus Sinularia. They co-occur with 14-membered macrocyclic 3(2H)-furanone-based norcembranoids, all of which lack a C18 carbon substituent in comparison with C-20-cembranoids. The polycyclic norcembranoids have structural features in common with the better-known C-20-cembranoid diterpenes plumarellide, mandapamate and rameswaralide. No synthetic studies or suggestions as to the origins of these novel polycyclic norcembranoids in Nature have been forthcoming. This review summarises the structural relationships that are found between polycyclic norcembranoids and their macrocyclic congeners. It then poses the question: how and when does Nature expel a C18 carbon substituent from a C-20-cembranoid precursor during the elaboration of macrocyclic norcembranoids? A number of suggestions and possibilities are then offered, involving both anionic and radical intermediates. Finally, the review speculates on the range of competitive transannular carbon-to-carbon bond-forming reactions that may be used as key steps in the elaboration of polycyclic norcembranoids from their macrocyclic precursors.