Elucidation of the biosynthetic origin of the anti-inflammatory pseudopterosins

The pseudopterosins are a family of diterpene glycosides isolated from the gorgonian coral Pseudopterogorgia elisabethae. These metabolites exhibit potent anti-inflammatory activity, and this review describes our efforts to elucidate their biosynthetic origin. A radioactivity-guided isolation was used to identify the terpene cyclase product. In addition, a detailed NMR-guided search for potential biosynthetic intermediates identified metabolites which were tested by incubating H-3-labeled analogues with a cell-free extract of the coral. All labeled metabolites were generated biosynthetically, and radiochemical purity was established by a combination of HPLC purification and derivatization. In summary, pseudopterosins are produced by a cyclization of geranylgeranyl diphosphate to elisabethatriene, aromatization to erogorgiaene, two successive oxidations to 7,8-dihydroxyerogorgiaene and a glycosylation to afford a seco-pseudopterosin as a key intermediate. A dehydrogenation leads to amphilectosins which undergo ring closures to yield the pseudopterosins.