A strategy towards the synthesis of plumarellide based on biosynthesis speculation, featuring a transannular 4+2 type cyclisation from a cembranoid furanoxonium ion intermediate

Abstract In studies towards a biomimetic synthesis of plumarellide 1 , acid-catalysed rearrangement of the furanobutenolide-based acetonide 10b led to the ring system 15b in plumarellide together with the cycloheptene-based ring system 11 found in rameswaralide 4 , in a combined yield of 60%. RCM of the ω-dienes 30a and 30b led to the macrocycles 38a and 38b , respectively with the Z -configuration. Treatment of the vinyl bromide/vinyl stannanes 32a and 47 under Stille conditions failed to give the macrocycles 31a and 48 , respectively. Reactions of the macrocycles 38a and 38b with TFA containing water produced the 5,6,7-tricyclic compounds 56a and 56b , respectively in >90% yield, instead of the plumarellide-based ring system 52 . A summary and perspective on possible pathways from the C-13 acetoxy furanocembranoid 66 and from the C13–C14 unsaturated enol ether/cyclic hemiketal 9 / 59 to plumarellide 1 in vivo is given.