Determination of relative and absolute configuration in the annonaceous acetogenins

Although tremendous progress has been made in this area, several stereochemical issues remain unaddressed in the Annonaceous acetogenins. The most obvious of these is the fact that there is still no general way to determine the configuration of C(36) in the A1 subunit—that is, the α, β-unsaturated lactone having no hydroxyl groups in its vicinity. The absolute configuration at this center has been determined for uvaricin by degradation, but as mentioned earlier, this approach may not be practical in all cases. However, the absence of other stereogenic centers on the A1 subunit and the remoteness of this substituent from other functionality present no small challenge to development of a more general method. In addition, although stereochemical information for portions of the B3 unit (nonadjacent bis-THF) is available, the complete relative configuration of the subunit as a whole remains unsolved. Despite these limitations, however, a wealth of information now exists on the stereochemical features of the Annonaceous acetogenins, and the complete relative and absolute configuration has been solved for several members of this class. The tremendous value and potential of NMR-based strategies and arguments is clear.