Small molecule synthesis usually relies on procedures highly customized for each target. A broadly applicable automated process could greatly increase the accessibility of this class of compounds to enable investigations of their practical potential. Here we report the synthesis of 14 distinct classes of small molecules using the same fully automated process. This was achieved by strategically expanding the scope of a building block-based synthesis platform to include even Csp3-rich polycyclic natural product frameworks and discovering a catch-and-release chromatographic purification protocol applicable to all of the corresponding intermediates. With thousands of compatible building blocks already commercially available, many small molecules are now accessible with this platform. More broadly, these findings illuminate an actionable roadmap to a more general and automated approach for small molecule synthesis.

The choice is yours: The first total synthesis of the antioxidant carotenoid synechoxanthin was achieved through a novel iterative cross‐coupling approach in which the polarity of the bifunctional building blocks is reversed to match the preferred polarity for CC bond formation (see scheme). The convergent, stereocontrolled, and flexible nature of this synthesis enables systematic studies of the biological activities of this natural product.

Sie haben die Wahl: Die erste Totalsynthese des antioxidativen Carotenoids Synechoxanthin wurde mithilfe einer neuartigen iterativen Kreuzkupplung erreicht, bei der die Polarität der difunktionellen Bausteine so umgekehrt wird, dass sie die für die C‐C‐Bindungsbildung bevorzugte Polarität haben. Diese konvergente, stereokontrollierte und flexible Synthese schafft die Voraussetzungen für systematische Studien der biologischen Aktivität dieses Naturstoffs.