Expanding the Synthetic Toolbox through Metal–Enzyme Cascade Reactions

Abstract

The combination of metal-, photo-, enzyme-, and/or organocatalysis provides multiple synthetic solutions, especially when the creation of chiral centers is involved. Historically, enzymes and transition metal species have been exploited simultaneously through dynamic kinetic resolutions of racemates. However, more recently, linear cascades have appeared as elegant solutions for the preparation of valuable organic molecules combining multiple bioprocesses and metal-catalyzed transformations. Many advantages are derived from this symbiosis, although there are still bottlenecks to be addressed including the successful coexistence of both catalyst types, the need for compatible reaction media and mild conditions, or the minimization of cross-reactivities. Therefore, solutions are here also provided by means of catalyst coimmobilization, compartmentalization strategies, flow chemistry, etc. A comprehensive review is presented focusing on the period 2015 to early 2022, which has been divided into two main sections that comprise first the use of metals and enzymes as independent catalysts but working in an orchestral or sequential manner, and later their application as bionanohybrid materials through their coimmobilization in adequate supports. Each part has been classified into different subheadings, the first part based on the reaction catalyzed by the metal catalyst, while the development of nonasymmetric or stereoselective processes was considered for the bionanohybrid section.

Chemoenzymatic cascade reaction as a sustainable and scalable access to para-quinols

“…The phenomenon of the changed activity of the metal catalyst as a result of interaction with a protein remains in agreement with the literature reports regarding artificial metalloenzymes. 30,39–41…”

“…The phenomenon of the changed activity of the metal catalyst as a result of interaction with a protein remains in agreement with the literature reports regarding artificial metalloenzymes. 30,[39][40][41] To gain a deeper understanding of the studied process, the reaction time course was recorded (Fig. 2) under optimised conditions (Table 2, entry 11).…”

Status check: biocatalysis; its use with and without chemocatalysis. How does the fine chemicals industry view this area?

“…In terms of recognized potential for merging bio-and chemo-catalysis, concrete examples reported using physical or chemical compartmentalization were offered to the interviewees with some of the seminal work as already described in the literature. 8 The relatively recent literature on the topic 3,9 can make the field of chemoenzymatic catalysis difficult to grasp for nonexperts and non-practitioners. Nonetheless, the perception was that it is no longer considered low hanging-fruit to just improve sustainability performance by recognizing an obvious need for improvement in this area, and then to rapidly design a suitable strategy to generate those improvements.…”

“…Several review articles point out that these two approaches to organic synthesis, while previously considered occupants of separate worlds, have actually been in hand for years. 3,9 People and culture are integral parts of the equation for adoption and eventually, success in these areas. Taken individually, significant progress can be achieved but alignment is not yet anywhere close to being optimal.…”

White & grey biotechnologies for shaping a sustainable future

“…174 Metal-enzyme cascade reactions have been comprehensively reviewed. 175 Gantz et al discussed the use of water-in-oil emulsion droplets for screening biocatalysts. 176 Working with picolitre volumes means a tremendous reduction in volumes over the popular 96-well plate format.…”