Synthetic studies of neoclerodane diterpenes from Salvia divinorum: Selective modification of the furan ring

A synthetic sequence has been developed to selectively functionalize the furan ring of the natural product salvinorin A ( 2a). The synthetic routes described convert the furan ring in 2a into an N-sulfonylpyrrole, oxazole or an oxadiazole. In addition, a procedure has been found to remove the furan skeleton completely. Biological results indicate that replacement of the furan ring with an N-sulfonylpyrrole leads to reduced affinity and efficacy at κ opioid receptors.