The total synthesis of membrarollin

A model adjacent bis-THF compound has been prepared with the installation of the first THF ring by a chiral auxiliary directed oxidative cyclisation of 1,5,9-dienyne 4.24 by potassium permanganate. The second THF ring was introduced by an acyl perrhenate cyclisation of hydroxyl-alkene 4.28. A crystal structure of the adjacent bis-THF product was obtained which showed the unexpected trans ring formed in the second cyclisation. The central adjacent bis-THF core of the Annonaceous acetogenin membrarollin was established via a permanganate promoted selective oxidative cyclisation of 1,5,9-triene 5.26 followed by a base-induced cyclisation of cyclic sulphate 5.35. Elaboration of the central core to terminal alkene 5.39 allowed the introduction of the butenolide fragment by Trost’s ruthenium catalysed Alder-ene reaction. Selective alkene reduction completed the synthesis of membrarollin.