Hemisynthesis of Oxetane-Containing Neoclerodane Diterpenoids

The hemisynthesis of the 4α,19-oxetane-containing neoclerodane diterpenoids 25 and 27, has been achieved from 19-acetylgnaphalin (4). Oxetane ring formation has been accomplished by intramolecular oxirane ring opening on the 4β,18-epoxy-neoclerodane 23, which yields derivative 25, and by electrophilic cyclization of the Δ4(18) homoallylic alcohol 26, which proceeds exclusively via the 4-exo mode, for obtaining the 18-iodo-4α,19-oxetane 27. The twisted boat conformation of ring A in derivative 27 favours an intramolecular nucleophilic substitution reaction yielding compound 28, which possesses a very interesting tetracyclic moiety in its structure. From the Δ4(18) unsaturated intermediate 21, access to Δ3-neoclerodane diterpenoids like 30 has been gained. The electrophilic cyclization of the Δ3 isomer 31 goes through a 5-endo mode exclusively, to form the 3α,19-epoxy-neoclerodane 33.