Synthesis of the non-adjacent bis-THF core of cis-sylvaticin using a double oxidative cyclisation

A short synthesis of the non-adjacent bis-THF core of the Annonaceous acetogenin cis-sylvaticin (1) is described. C-2 Symmetrical (Z,E,E,Z)-and (E,E,E,E)-tetraenes 5 and 6 were synthesised in six and three steps respectively from (1E,5E,9E)-cyclododeca-1,5,9-triene. Subsequent permanganate promoted asymmetric bi-directional oxidative cyclisation of tetraene 5 was used to create the non-adjacent bis-THF core of 1, installing seven of the nine stereogenic centres present in the natural product in a single step. Desymmetrisation of the oxidative cyclisation product by mono-tosylation gave access to a C11-C32 fragment of cis-sylvaticin