Chemical Synthesis of Aspidosperma Alkaloids Inspired by the Reverse of the Biosynthesis of the Rhazinilam Family of Natural Products

摘要

Pyrrole and pyrroldine heterocycles are ubiquitous structural features in natural products. Nature's biosynthetic machinery often synthesizes the pyrrole functionality in these molecules from a saturated pyrrolidine as part of its metabolic degradation pathway. Interestingly, the chemical synthesis of substituted pyrroles is usually more straightforward in comparison to that of the corresponding pyrrolidines; the saturated hydrocarbon framework of pyrrolidine is relatively unreactive, usually requiring the presence of additional functional groups to install a particular substituent, thus rendering the synthesis of such compounds difficult in comparison to their aromatic congeners. Therefore, the transformation of a highly substituted pyrrole into an architecturally complex pyrrolidine becomes an attractive and potentially powerful strategy for total synthesis (Figure 1A).