TOTAL SYNTHESIS OF THE INSECT ANTIFEEDANT AJUGARIN I AND DEGRADATION STUDIES OF RELATED CLERODANE DITERPENES

Article abstract of DOI:10.1016/S0040-4020(01)88114-X

The first total synthesis of the diterpene clerodane insect antifeedant ajugarin I (1) has been achieved.The key step of the synthesis discloses the use of the 1,3-dithiolane unit to stereochemically direct the conjugate addition of a but-3-enyl cuprate to set in place the C-10 sp₃ carbon centre.The trans-fused ring geometry was obtained by conjugate addition of a vinyl cuprate to an enone and regio and stereoselectively trapping the resulting enolate with formaldehyde.Introduction of the necessary butenolide side chain was achieved by conjugate addition of a sulphone stabilised anion to ethyl-4-(t-butyldimethylsilyloxy)but-2-ynoate followed by work-up with fluoride.Final hydroxyl directed epoxidation was not specific giving both the natural product ajugarin I and its 4-epi isomer.Chemical modification of the insect antifeedant clerodin hemiacetal afforded a series of side chain modified structures for biological evaluation.