Hemisynthesis of oxetane-containing neoclerodane diterpenoids

The hemisynthesis of the 4 alpha,19-oxetane-containing neoclerodane diterpenoids 25 and 27, has been achieved from 10-acetylgnaphalin (4). Oxetane ring formation has been accomplished by intramolecular oxirane ring opening on the 4 beta, 18-epoxy-neoclerodane 23, which yields derivative 25, and by electrophilic cyclization of the Delta(4(18)) homoallylic alcohol 26, which proceeds exclusively via the 4-exo mode, for obtaining the 18-iodo-4 alpha,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 Delta(4(18)) unsaturated intermediate 21, access to Delta(3) neoclerodane diterpenoids like 30 has been gained. The electrophilic cyclization of the Delta(3) isomer 31 goes through a 5-endo mode exclusively, to form the 3 alpha,19-epoxy-neoclerodane 33. (C) 2000 Elsevier Science Ltd. All rights reserved.