Felix C. Raps

Biocatalysis has revolutionized chemical synthesis, providing sustainable methods for preparing various organic molecules. In enzyme-mediated organic synthesis, most reactions involve molecules operating from their ground states. Over the past 25 years, there has been an increased interest in enzymatic processes that utilize electronically excited states accessed through photoexcitation. These photobiocatalytic processes involve a diverse array of reaction mechanisms that are complementary to one another. This comprehensive review will describe the state-of-the-art strategies in photobiocatalysis for organic synthesis until December 2022. Apart from reviewing the relevant literature, a central goal of this review is to delineate the mechanistic differences between the general strategies employed in the field. We will organize this review based on the relationship between the photochemical step and the enzymatic transformations. The review will include mechanistic studies, substrate scopes, and protein optimization strategies. By clearly defining mechanistically-distinct strategies in photobiocatalytic chemistry, we hope to illuminate future synthetic opportunities in the area.

The folding and cyclization of poly-β-carbonyl chains controlled by the intricate enzymatic polyketide synthase machinery results in a remarkable diversity of aromatic natural products. Synthetic methods that allow for the preparation of highly reactive polyketide chains while governing their folding in ensuing cyclizations likewise lead to versatile divergent preparations of aromatic scaffolds valuable for numerous applications. Although biomimetic polyketide cyclizations have repeatedly been applied in the total synthesis of polyphenol natural products, their utility for the preparation of the broad range of polyaromatic architectures has yet to reach its full potential. This Minireview highlights some of the virtues of applying polyketide logic to the retrosynthetic analysis of polycyclic aromatic scaffolds, the increasing accessibility of precursors, and the potential of small-molecule catalysts for controlling polyketide cyclizations to provide polyaromatic scaffolds.

Two [2]rotaxanes have been assembled in water from modular subunits through Cu I ‐catalyzed azide–alkyne “click” chemistry. For this purpose, 2,6‐disubstituted naphthalene axles with solubilizing oligo(ethylene glycol) (OEG) chains ( n = 1–5) and propargyl terminal groups were synthesized and examined for their propensity to form inclusion complexes with a dicationic Diederich‐type cyclophane host. The dependence of pseudorotaxane formation on the linkers between the naphthalene core and OEG chains, and in the case of ester linkers on different spacer lengths, was analyzed by titration experiments. In addition, the inclusion complexes of two [2]rotaxanes were trapped by using a water‐soluble azide‐functionalized stopper. Repetitive chromatography finally enabled the isolation of both mechanically interlocked [2]rotaxanes.

Enzymes are invaluable tools for solving challenges in synthetic organic chemistry. Beyond replicating native reactivity patterns, modern directed evolution strategies have enabled chemists to efficiently survey chemical space to identify enzyme families capable of catalyzing non-natural reactions. While methods often focus on chemo-, enantio-, and regiocontrol, there are a growing number of examples that describe reactivity patterns and reaction mechanisms that were previously unknown in the synthetic literature. In this Perspective, we will explore examples of such emergent mechanistic pathways of enzymes in the context of synthetic precedents, emphasizing the remarkable versatility of diverse enzyme active sites in controlling unprecedented transformations.