Annonaceous acetogenins are a rapidly growing class of natural products with a vast array of biological activities including anti-tumor and pesticidal promise. This proposal describes a versatile synthetic strategy using catalytic ring closing metathesis (RCM) for accessing several adjacent bis-THF containing Annonaceous acetogenins. The use of RCM is extended to the synthesis of both the tetrahydrofuran segment as well as the butenolide terminus common to many of the acetogenins as well as a host of other natural and unnatural targets. The outlined proposal presents alternative protocols that deal with both symmetrical bis-THF core structures as well as those lacking complete symmetry. A complete proposed synthesis of a model target asimicin is presented.
