Total synthesis and structure confirmation of the Annonaceous acetogenins 30(S)-hydroxybullatacin, uvarigrandin A, and 5(R)-uvarigrandin a (narumicin I?)

A synthesis of the bistetrahydrofuran Annonaceous acetogenins 30(S)-hydroxybullatacin, uvarigrandin A, and 5(R)-uvarigrandin A through application of a previously disclosed four-component modular approach is described in which extended core segments are coupled to a C4- or C5-hydroxy butenolide terminus. The butenolide termini segments were prepared from (S)- or (R)-malic acid. Spectral properties of synthetic 30(S)-hydroxybullatacin and uvarigrandin A, as well as their Mosher ester derivatives, were in close agreement to the reported values for the natural substances. The synthetic 5(R)-uvarigrandin A is possibly identical to narumicin I, but subtle differences in the reported NMR spectra prevented an unambiguous assessment of this point.