Natural Furanocembranoids. A Synthetic Approach to Lophotoxin based on an Acyl Radical Macrocyclisation Strategy

All articles of this category A concise synthesis of the furan-containing macrocyclic (cembranoid) ring system 8 (10-isopropenyl-3,7,13-trimethyl-15-oxabicyclo [10.2.1]pentadeca-2,6, 12,14-tetraene) found in Iophotoxin (1) and other members of this family of irreversible nicotinic receptor antagonists, is described. The synthesis features a 14- endo trig cyclisation from an unsaturated acyl radical intermediate incorporating a terminal conjugated enone moiety, viz 10 , leading to the macrocycle (5 E ,9 E )-13-isopropenyl-2,6,10-trimethylcyclotetradeca-5, 9-diene-2,4-dione (9) , followed by acid-catalysed furan ring formation from the resulting 1,4-dione system in 9 (Scheme 1).