Total Synthesis of Neohedycaryol. Its Possible Role in the Biosynthesis of Eudesmane Sesquiterpenes

Abstract

The total synthesis of neohedycaryol (4), the C(9)-C(10) double bond regioisomer of the germacrane sesquiterpene hedycaryol, was accomplished in 10 steps from the known dione 6. A Marshall fragmentation of the intermediate mesylate 14 was used to prepare the trans,trans-cyclodeca-1,6-diene ring present in neohedycaryol. During the synthesis of 14, a pronounced example of through-bond interactions (TBI) was observed. The preferred elongated chair conformation of neohedycaryol was demonstrated spectroscopically and by chemical conversion into alpha-, beta-, and gamma-eudesmol. These findings indicate that the occurrence of neohedycaryol as a precursor in the biosynthesis of epi-eudesmanes as proposed in the literature is unlikely. The preference of neohedycaryol for the elongated chair conformation further shows that the compound occupies the meso form. This implies that neohedycaryol may act as a precursor in the biosynthesis of both ent- and usual eudesmanes.