Catalytic Cascade Reactions Inspired by Polyketide Biosynthesis

Aldol reactions belong to the most important methods for carbon–carbon bond formation and are also involved in one of the most astonishing biosynthetic processes: the biosynthesis of polyketides governed by an extraordinarily sophisticated enzymatic machinery. In contrast to the typical linear or convergent strategies followed in chemical synthesis, this late-stage catalysis concept allows Nature to assemble intermediates that are diversified into a broad range of scaffolds, which assume various crucial biological functions. To transfer this concept to small-molecule catalysis to access products beyond the natural systems, a stepwise approach to differentiate increasingly complex substrates was followed by investigating arene-forming polyketide cyclizations. An outline of our efforts to develop and apply these concepts are presented herein.