A Retrosynthesis Approach for Biocatalysis in Organic Synthesis

Abstract

For the planningo fa no rganic synthesis route, the disconnection approach guided by retrosynthetic analysis of possible intermediates and the chemical reactions involved, backt or eady available starting materials, is well established. In contrast, such concepts just get developed for biocatalytic routes. In this Review we highlightf unctional group interconversions catalyzed by enzymes. The article is organized rather by chemical bonds formed-exemplified for CÀN, CÀO-and CÀC-bonds-and not by enzyme classes, covering ab road range of reactions to incorporate the desired functionality in the target molecule. Furthermore, the successful use of biocatalysts, also in combination with chemicals teps, is exemplified for the synthesis of various drugs and advanced pharmaceutical intermediates such as Crispine A, Sitagliptina nd Atorvastatin. This Reviewa lso provides some basic guidelines to choose the most appropriate enzyme for at argeted reaction keepingi nm ind aspects like commercial availability,c ofactor-requirement, solventt olerance, use of isolated enzymes or whole cell recombinant microorganisms aiming to assist organic chemists in the use of enzymesf or synthetic applications.

Accessing Enantiopure Epoxides and Sulfoxides: Related Flavin‐Dependent Monooxygenases Provide Reversed Enantioselectivity

“…Enzyme driven catalysis is of increasing interest for biochemical and industrial applications. [1,2,3] Biocatalysts can work under mild conditions, they utilize non-toxic cofactors and often produce less waste, or side products, as they are often chemo-, regioand enantioselective towards a substrate or product. Some enzymes allow reactions that are not possible under regular conditions.…”

“…As a consequence, they are currently considered as candidates for biotechnological processes. [1,3,9,44,45] However, limited activity, stability and conversion of bulky substrates have been issues within this group of flavoproteins. Furthermore, changing or even optimizing the enantioselectivity of these biocatalysts is of high interest.…”

10 Volumes of ChemCatChem, a Cross Section of Catalysis Research from ChemPubSoc Europe

“…Moreover, in the past decade we could recognize that enzymes are being increasingly used in combination with a variety of chemocatalysts, as well as in multistep enzyme cascades . These trends are further fostered by recently published reviews, and a book on the integration of enzymatic steps in retrosynthesis planning, a concept well established in organic syntheses for decades. These developments will for sure contribute substantially to the understanding of organic chemists on the use of certain enzymes to introduce desired functionalities and their successful implementation into multistep routes.…”

“…Perhaps this differentiation will become obsolete in the future. In recent years we have seen an explosion of novel reactions catalyzed by enzymes . The combination of a computational and an experimental approach has become state‐of‐the‐art, which, guided by scientific analysis, enables the design and development of improved catalysts.…”

The Promises and the Challenges of Biotransformations in Microflow

“…Current efforts toward more sustainable production systems and biobased products have spurred intense discovering and engineering of more specific and stable biocatalysts, as well as the establishment of novel chemoenzymatic routes . Although several industrial biotransformations demonstrate the benefits of biocatalysis for sustainable production of food, pharmaceuticals, fine and platform chemicals, there is still a huge untapped potential of catalytic activities available for the targeted valorization of raw materials including waste streams and CO 2 .…”